International Journal of Applied Pharmaceutics

EXPLORING POTENTIAL OF NOVEL HETEROCYCLIC COMPOUNDS AND THEIR STRUCTURE-ACTIVITY RELATIONSHIP IN PROSTATE CANCER TREATMENT

2024-06-27T16:36:07+0530

Prostate cancer is one of the leading causes of male death globally, and its overall incidence flaunts a rising trend over the years. Currently available treatment modalities for prostate cancer suffer from severe toxicity, unpredictable efficacy, high costs, and the emergence of resistance towards anti-cancer compounds. This substantiates the need to develop novel and potent anti-proliferative agents against prostate cancer. Multiple cellular mechanisms underlie the development of prostate cancer and, thus, multiple druggable targets. In recent years, researchers have been conducting a myriad of investigations in this direction. This work recapitulates the synthesis of 78 such molecules based on recent references. These compounds are classified and tabulated according to the moiety that they possess. Further, the review study highlights the potent member of each chemical class. In addition, the review provides fundamental insights into the design and development of such compounds through the structure-activity relationship of each series of compounds, thereby unlocking new doors for future exploration.

PHARMACEUTICAL NANOCRYSTALS: AN EXTENSIVE OVERVIEW

2024-08-05T17:12:28+0530

In pharmaceutical development, pharmaceutical nanocrystals sized between 10 and 1000 nanometers have been found to hold promise in improving drug solubility. Since they comprise only the active pharmaceutical ingredient, nanocrystals have dramatically increased surface area-to-volume ratios, ensuring improved in vitro dissolution and solubility profiles.

In view of their strengths and limitations, different production strategies have been reviewed: methods of size reduction such as wet milling and high-pressure homogenization; the bottom-up approaches of controlled precipitation and supercritical fluid technology; and efficient ways to stabilize nanocrystal formulations aided by excipients like surfactants and polymers.

Techniques used in this characterization of nanocrystals include size analysis, surface-charge measurement, and assessment of crystalline structure. The routes of administration, such as oral, injectable, inhaled, and topical application, are reviewed alongside commercially successful products and clinical trials.

This work reviews dynamic regulatory scenarios and current challenges of large-scale production, long-term stability, and nanotoxicity evaluation. In addition, it addresses the emerging trends in nanocrystal technology in the field of personalized medicine, targeted drug delivery, and theranostic approaches associated with how nanocrystals can help optimize the outcome of a patient in drug delivery systems.

SYNERGY OF SCIENCE AND TRADITION: A NANOTECHNOLOGY-DRIVEN REVOLUTION IN NATURAL MEDICINE

2024-02-29T12:36:31+0530

Usage of plants to treat various ailments is part and parcel of our tradition and culture. Most marketed formulations are directly or indirectly derived from plants only. Herbal plants are potential therapeutic agents against most life-threatening diseases. Despite these advantages, herbal medicines fail clinical trials due to their low aqueous solubility and low bioavailability. To get the maximum benefits out of herbal plants, we must incorporate medicinal herbs in nanotechnology. The nanotechnology approach not only protects herbal medicines in the body but also aids in delivering the same to the site of action with sustained release. The formulation of herbal nanomedicines will be a breakthrough in treating life-threatening diseases and will also aid in the delivery of drugs that conventionally cannot cross the Blood-Brain Barrier (BBB). The review summarizes the recent advancements of the various nanocarriers loaded with herbal extracts/Phytoconstituents developed to treat various diseases, especially cancer. It also highlights the regulatory requirements for herbal nanomedicines.

THERAPEUTIC USE OF ALPHA-LIPOIC ACID SUPPLEMENTATION: A REVIEW ON CURRENT USE AND FUTURE PROSPECTIVE

2024-05-06T00:32:23+0530

Alpha-lipoic acid (ALA, thioctic acid, 5-(1,2-dithiolan-3-yl) pentanoic acid) is an organosulfur compound produced by plants, humans, and animals. ALA plays a crucial role in mitochondrial bioenergetics reactions. It is a natural antioxidant and a dithiol compound. ALA is a coenzyme that plays a crucial role in the function of pyruvate and Alpha-ketoglutarate dehydrogenase complexes found in mitochondria. ALA has cytotoxic and antiproliferative effects on several cancers, including Polycystic Ovarian Syndrome (PCOS). Most of ALA's clinical applications come from its antioxidant properties, but it also shows potential in treating female and male infertility. Although ALA can potentially be a therapeutic agent, its pharmacokinetic profile limits its effectiveness. Research suggests that ALA has a short half-life and low bioavailability (around 30%) because it gets broken down in the liver, has reduced solubility, and is unstable in the stomach. Liquid formulations have higher bioavailability and plasma concentration than solid dose forms. This review covers the current clinical evidence on using ALA to prevent, manage, and cure numerous disorders, including diabetic neuropathy, obesity, central nervous system-related ailments, and pregnancy abnormalities.

RENOPROTECTIVE POTENTIAL OF FLAVONOIDS-RICH AGAINST DOXORUBICIN-INDUCED IN ANIMAL MODELS: A REVIEW

2024-06-10T01:53:43+0530

Cancer significantly impacts human health, affecting one in five people during their lifetime. While chemotherapeutic agents like doxorubicin are crucial in treating various cancers, they are also associated with severe side effects, including nephrotoxicity. This review examines the renoprotective potential of flavonoids against doxorubicin-induced renal damage in animal models. Doxorubicin works by intercalating Deoxyribo Nucleic Acid (DNA) and making Reactive Oxygen Species (ROS), which cause apoptosis and the death of cells. A thorough literature analysis was done to collect relevant papers on the impact of flavonoid-rich therapies as renoprotective agents against doxorubicin-induced nephrotoxicity. Databases such as Google Scholar, Scopus, PubMed, Springer, Wiley Online Library, and ScienceDirect were searched using keywords including "flavonoids, doxorubicin, renoprotective, nephrotoxicity, and animal model," focusing on publications from 2014 to 2024. Flavonoids are diverse polyphenolic compounds in many plants with significant pharmacological properties such as antioxidant, anti-inflammatory, and anticancer effects. This review highlights the renoprotective potential of flavonoids like quercetin, rutin, kaempferol, morin, luteolin, apigenin, hesperidin, naringenin, diosmin, and anthocyanins. These compounds reduce renal toxicity through mechanisms that decrease ROS, lipid peroxidation, mitochondrial permeability, and apoptosis.

IMPACT OF LIGAND CONJUGATION OF PHYSICOCHEMICAL ATTRIBUTES OF POLYMERIC NANOPARTICLES OF ATYPICAL ANTIPSYCHOTIC DRUG FOR NOSE-TO-BRAIN DELIVERY

2024-07-09T23:23:05+0530

Objective: To formulate and characterize the ligand-conjugated chitosan nanoparticles of Ziprasidone Hydrochloride (ZH) and compare with its plain chitosan nanoparticles.

Methods: Transferrin (Tf) conjugated Chitosan Nanoparticles (CH-NP) containing ZH were prepared by ionotropic gelation method by using modified chitosan and Tf. Physicochemical attributes of nanoparticles which can potentially impact the nose-to-brain delivery were evaluated.

Results: The Tf-CH-NP has demonstrated 207.1 nm mean particle size, 87.6% entrapment efficiency with a release of 89.34% at 24 h and has shown about 2.22 times more release than drug suspension and about 4.5% more than plain CH-NP. The similar trend was observed in Ex vivo nasal permeation study. Its acceptability was shown in histomorphology study, where a minimal inflammation seen, that might be due to the pH of the formulation. There is deeper penetration with Tf-CH-NP, which is more promising for penetration into brain.

Conclusion: The formulated Tf-CH-NP has a greater potential due to ligand conjugation to reach the brain and, facilitate targeted delivery and enables better treatment of schizophrenia at minimal doses.

EVALUATION OF AN ANTI-DANDRUFF SHAMPOO INCORPORATING ETHANOL EXTRACT FROM CORN SILK (ZEA MAYS L.) AGAINST CANDIDA ALBICANS FUNGUS: FORMULATION AND ACTIVITY ASSESSMENT

2024-07-02T13:43:17+0530

Objective: The aim of this study was to investigate the effectiveness of corn silk (Zea mays L.) extract as an antifungal ingredient in shampoo formulation for treating dandruff caused by Candida albicans.

Methods: Plant identification, sampling, preparation of simplisia, phytochemical screening, simplisia characterization, ethanol extraction of corn silk, and the formulation of shampoos with extract concentrations of 5%, 10%, and 15%, alongside blank and positive controls. The formulations underwent physical evaluation, irritation testing, and antifungal activity testing using the disc diffusion method.

Results: The corn silk shampoo formulations were stable during storage, non-irritating, was in thick liquid form with yellowish to brown colour, corn scent, had pH between 5.0-5.8, foaming capacity at 10.3-13.0 cm, with the viscocity ranging 1967-2224 cPs, means it met the required standards for shampoo formulation and characterization. Antifungal testing revealed inhibition zone diameters of 0 mm for the blank (F0), 7.87 mm for F1 (5%), 9.46 mm for F2 (10%), 15.89 mm for F3 (15%), and 18.71 mm for the positive control (C+), with a one-way ANOVA test indicating a significant difference compared to the negative control.

Conclusion: Corn silk extract could be effectively formulated into an antifungal shampoo, with the 15% concentration being the most effective against Candida albicans, highlighting its potential as a natural ingredient for anti-dandruff shampoos.

FORMULATION AND IN VITRO TESTS OF KETOPROFEN NANOSUSPENSION USING THE MILLING METHOD WITH POLYMER VARIATIONS

2024-06-21T22:24:21+0530

Objective: The aim of this research was to formulate ketoprofen nanosuspension with a variety of polymers and to compare the dissolution rate of the nanosuspensions with ketoprofen suspension.

Methods: Ketoprofen nanosuspension was formulated by milling method using a different polymer such as Polyvinyl Pyrrolidone (PVP) K-30 (F1), Polyvinyl Alcohol (PVA) (F2) and Hydroxy Propyl Methyl Cellulose (HPMC) (F3). Nanosuspensions were prepared and characterized, including organoleptic, pH, particle size, zeta potential, Polydispersity Index (PI), specific gravity, crystalline state determination, physical stability at room temperature for 3 mo, and in vitro dissolution test compared with ketoprofen suspension.

Results: The ketoprofen nanosuspensions with PVP K-30 and PVA showed stable preparations, while those with HPMC showed less stability, as indicated by sedimentation during storage. The particle size values of PVP K-30 and PVA were 10.004±0.03 nm; and 9.560±0.01 nm; zeta potential and polydispersity index values met the test requirements. The dissolution rate of the ketoprofen nanosuspensions was higher with a cumulative of F1, F2, and F3 were 83.35%; 85.00%, and 81.09% after 60 min, while the ketoprofen suspension was only 7.62%.

Conclusion: The milling method of ketoprofen nanosuspensions with PVP and PVA has more stable physical characteristics than nanosuspension with HPMC. The ketoprofen nanosuspensions have a higher dissolution rate than the ketoprofen suspension.

PHARMACOKINETIC STUDY OF HY-FOLIC® AND FOLIC ACID IN HEALTHY VOLUNTEERS

2024-06-23T19:04:17+0530

Objective: HY-FOLIC® is the active form of Folic Acid (FA) produced by PT Simex Pharmaceutical Indonesia containing (6S)-5-Methyltetrahydrofolate (5-MTHF). We evaluated the pharmacokinetic profiles of HY-FOLIC® versus FA after single oral administration in healthy volunteers.

Methods: A randomized, open-label, 2-way crossover, single-dose design was conducted on 12 healthy subjects with two steps. In the first step, 6 subjects were given 1100 mcg of HY-FOLIC^®(1.3 μmol), and 6 subjects were given an equimolar dose of 600 mcg of FA (1.3 μmol) in a fasting condition. Blood samples were taken before, and at 1, 2, 3, 4, 5, 6, 7, and 8 h after administration of products for measurement of peak concentration (Cmax), the Area Under the Curve at t-time (AUCt) and infinite time (AUCinf). After a washout period of 14 d, the same procedure was repeated in which the first 6 subjects received FA, and the second 6 subjects received HY-FOLIC^®. Pharmacokinetic data of 5-MTHF and Unmetabolized Folic Acid (UMFA) were compared with paired t-tests.

Results: Cmax of 5-MTHF (mean±SD) following administration of HY-FOLIC^®and FA were 46.91+28.16 vs 22.61+15.73 nmol/l, respectively (p=0.000); the AUCt were 214.47+183.46 vs 112.93+112.11 h. mmol/l (p=0.001). Conversely, Cmax of UMFA were 9.49+7.89 vs 21.97+14.79 nmol/l (p=0.003); AUCt 33.29+39.34 vs 78.16+58.93 h. nmol/l (p=0.001).

Conclusion: HY-FOLIC^®is much more bioavailable than FA as indicated by much higher Cmax and AUCt of the active form of 5-MTHF.

A NETWORK PHARMACOLOGY-BASED DRUG REPURPOSING STUDY OF LEVETIRACETAM UNCOVERS ITS INTERACTION WITH MULTI-DRUG TARGETS IN PARKINSON'S DISEASE

2024-07-02T14:19:02+0530

Objective: The current study utilized network pharmacology to examine how Levetiracetam interacts with specific drug targets associated with Parkinson's Disease (PD) treatment.

Methods: We used information from Kyoto Encyclopedia of Genes and Genome (KEGG) studies and Protein-Protein Interaction (PPI) pathway analysis to create a network that depicts the relationships between Levetiracetam and PD targets. Further investigation involved PPI analysis, molecular docking, and Molecular Dynamics (MD) simulation studies, ultimately pinpointing five protein targets. Their participation in pathways such as Ribonucleic acid Polymerase II-specific Deoxyribonucleic acid binding Transcription Factor Binding (Gene Ontology [GO]:0061629), Axon (GO: 0030424), and Excitatory Postsynaptic Potential was emphasized by GO and KEGG pathway enrichment. Additionally, Dopamine Receptor D2 (DRD2), Solute Carrier Family 6 Member 3 (SLC6A3), Glycogen Synthase Kinase 3 Beta (GSK3B), Poly (ADP-ribose) Polymerase 1 (PARP1) and Myeloperoxidase (MPO) were identified as protein targets through PPI and molecular docking analysis.

Results: The results of molecular docking showed that protein targets, SLC6A3, have highest binding affinity with Levetiracetam. The MD Simulation result of Levetiracetam-SLC6A3 docked complex represented the complex to be quite stable with few conformational changes in the SLC6A3 structure. DRD2, SLC6A3, GSK3B, PARP1, MPO were recognized as the likely protein targets of Levetiracetam for treating PD. SLC6A3 was considered as a target of Levetiracetam in PD.

Conclusion: Our study revealed the mechanism of Levetiracetam in the treatment of PD and can contribute to more effective treatment for the same. By identifying key protein targets, this research lays the groundwork for future studies that could further explore Levetiracetam’s efficacy.

OPTIMIZED SOLID LIPID NANOPARTICLES FOR ENHANCED ORAL BIOAVAILABILITY AND OSTEOGENIC EFFECT OF IPRIFLAVONE: FORMULATION, CHARACTERIZATION, AND IN VITRO EVALUATION

2024-06-26T11:01:01+0530

Objective: This study aimed to enhance the oral bioavailability of Ipriflavone (IP) and evaluate its osteogenic effect on human osteosarcoma cells (MG-63) by developing Ipriflavone-loaded Solid Lipid Nanoparticles (IP-SLN).

Methods: IP-SLNs were prepared using a modified solvent evaporation method with probe sonication. Formulation optimization employed Central Composite Design (CCD) with independent variables, including lipid amount, surfactant concentration, and sonication time. Characterization was performed using Transmission Electron Microscopy (TEM). In vitro drug release and ex vivo permeation studies were conducted to assess drug release kinetics and bioavailability. Cytotoxicity, Alkaline Phosphatase (ALP) activity, and calcium deposition studies on MG-63 cells evaluated osteogenic effects.

Results: TEM images showed round particles with an average diameter of 43.24±3 nm, a zeta potential of-9.53 mV, and a drug entrapment efficiency of 76.53±1.84%. In vitro drug release from IP-SLN was 79.02% compared to 14.21% from IP after 48 h, following the Korsmeyer-Peppas model and first-order kinetics. Ex vivo permeation of IP-SLN was approximately 2-fold higher than IP dispersion. Cytotoxicity studies revealed no toxicity on MG-63 cells. ALP activity and calcium deposition studies indicated that IP-SLN stimulated osteoblast differentiation, increasing alkaline phosphatase activity and mineralization. Pharmacokinetic studies demonstrated that IP-SLN increased the relative bioavailability by 515% compared to ipriflavone.

Conclusion: IP-SLN formulations significantly improved the oral bioavailability and osteogenic effects of ipriflavone on MG-63 cells, suggesting potential for novel therapeutic applications in osteoporosis treatment.

DEVELOPMENT AND EVALUATION OF CYCLODEXTRIN NANOSPONGES-BASED TOPICAL FORMULATION OF TAZAROTENE

2024-07-06T12:29:11+0530

Objective: Tazarotene is used as a topical retinoid for the treatment of acne, psoriasis and sun-damaged skin. But its topical formulation has many side effects, including itching, burning, dryness, redness, stinging, rash blistering, skin discoloration, peeling at the site of application and low bioavailability. The present study focuses on the reduction of side effects and enhancement of solubility and topical bioavailability of tazarotene by using cyclodextrin-based nanosponges.

Methods: Nanosponge of tazarotene were prepared by lyophilization method. The physiochemical characterization of plain nanosponges and drug-loaded nanosponges were performed using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and X-ray Diffractometer (XRD) studies. The drug-loaded nanosponges were incorporated into a carpool-based gel formulation. The prepared formulation was evaluated for viscosity, dissolution and stability. FTIR, DSC and XRD studies confirmed the formation of inclusion complex of tazarotene with nanosponges.

Results: The particle size of the drug-loaded nanosponges was found to be in the range of 156.72 to 163.48 nm. Transmission Electron Microscopy (TEM) images revealed the regular spherical shape of both the nanosponges that are unaffected even after drug encapsulation. The pH of the gel formulations was found to be in the range of 5.86 to 6.46. The gel formulation resulted in the diffusion of drug in controlled manner for up to 24 h. The in vitro dissolution studies revealed that nanosponges-based topical formulation had better results than the marketed product.

Conclusion: Thus, the study showed that nanosponge-based gel formulation can be a possible alternative to conventional formulations of tazarotene with enhanced bioavailability and skin retention characteristics for topical application.

OPTIMIZATION OF LC-MS/MS METHOD FOR THE SIMULTANEOUS DETERMINATION OF METFORMIN AND ROSIGLITAZONE IN HUMAN PLASMA WITH BOX-BEHNKEN DESIGN

2024-07-01T15:06:10+0530

Objective: The objective of this study was to develop a robust Liquid Chromatography – Tandem Mass Spectrometry (LC-MS/MS) methodology for the precise quantification of metformin and rosiglitazone in human plasma.

Methods: A Design of Experiments (DOE) framework was utilized, specifically employing a Box-Behnken experimental design, to optimize critical parameters such as Capillary voltage, Cone voltage, Desolvation temperature, and Collision energy. Sample preparation involved protein precipitation using acetonitrile, simplifying the procedure. Chromatography was performed with a mobile phase of 0.1% formic acid and acetonitrile (60:40 V/V) to enhance sensitivity and reproducibility. Quantification was achieved through Multiple Reaction Monitoring (MRM) of the transition’s m/z 130.1 → m/z 60.1 for metformin, m/z 358.2 → m/z 134.9 for rosiglitazone, and m/z 206.3 → m/z 59.9 for phenformin. The methodology was validated according to regulatory guidelines.

Results: The developed methodology demonstrated selectivity, linearity, accuracy, precision, recovery, and stability. The calibration curve showed linearity over the concentration range of 5 ng/ml to 1000 ng/ml for metformin and 1.5 ng/ml to 300 ng/ml for rosiglitazone. Accuracy and precision were within acceptable limits across calibration and quality control standards. Assessments of extraction recovery and matrix effects confirmed the robustness of the extraction procedure, with negligible interference from plasma components. Stability studies indicated that the method maintained acceptable limits for metformin and rosiglitazone concentrations under various storage and handling conditions.

Conclusion: The validated Liquid Chromatography – Tandem Mass Spectrometry (LC-MS/MS) methodology provides a reliable and accurate platform for the quantification of metformin and rosiglitazone in human plasma. This method shows potential applications in pharmacokinetic studies and clinical research, ensuring consistent performance in routine analysis.

PRELIMINARY STUDY ON ALGINATE CONCENTRATION AND ANTIBACTERIAL ACTIVITY OF PALMAROSA ESSENTIAL OIL

2024-07-06T13:55:49+0530

Objective: Palmarosa (Cymbopogon martinii (Roxb.)) essential oil has volatile active compounds, therefore, it requires modification of encapsulation to obtain optimum potency. This study investigated the relationship between various alginate concentrations in microencapsulation against the quality of the formula and antibacterial activity.

Methods: The study use Palmarosa Essential Oil (PEO) that distillated at Rumah Atsiri, Indonesia. Ionic gelation was used to prepare microencapsulations at different alginate concentrations of 0.5%, 0.75%, and 1.5%. The investigation involved Fourier Transform Infrared (FTIR), organoleptic, morphological, microencapsulated weight, Encapsulation Efficiency (EE), and antibacterial activity.

Results: The organoleptic observation results for all formulas are white in color, have a pronounced PEO scent, and contain spherical particles with macrometer-sized morphology similar to soft beads. The result FTIR showed that F1, F2, and F3 contain aromatic ring, primarily alcohol, alkene, alkyl, and alcohol. The results showed that F1, F2, and F3 were included in the microencapsulation range, namely 5-5,000 µm. Formula III had the greatest EE of 86.53±0.75% and antibacterial activity against Staphylococcus epidermidis and Pseudomonas aeruginosa, respectively showed inhibition zones with diameters of 12.30±0.16 mm and 7.60±0.24 mm.

Conclusion: This study revealed that the findings of this study demonstrate that the concentration of alginate in microencapsulation influences the properties and antibacterial activity of PEO. Higher alginate concentrations can lead to increased EE, particle size distribution, and ultimately leading to enhanced antibacterial activity.

AGOMELATINE ETHOSOMES FOR ENHANCED TRANSDERMAL DRUG DELIVERY

2024-07-07T15:58:23+0530

Objective: The current study aimed to prepare and optimize Agomelatine (AMN) ethosomes for enhanced transdermal drug delivery.

Methods: In this study cold method was employed to manufacture the AMN-loaded ethosomes with dissimilar quantities of Phosphatidyl Choline (PC): Cholesterol: Ethanol. Transmission Electron Microscopy (TEM) was employed to evaluate the appearance of the formed ethosomes. Other formulation parameters like vesicle size and zeta potential, polydispersity index, transition temperature, and entrapment efficiency were also investigated.

Results: The microscopy results showed that AMN ethosomes have a smooth surface. It was discovered that the AMN-3 formulation of transdermal ethosomes had 92.15±1.3 entrapment efficiency with good vesicle diameter. The release of agomelatine adhered to the zero-order release model. The polydispersity Index (PI) and zeta potential of the optimized formulation were found to be 0.209 and-14.09±1.95 mV, respectively. The maximum flux for the ethosome formulation (AMN-3) was 34.29 µg. h/cm². A 10.71 fold increment was observed in the bioavailability of optimized formulation than control (oral suspension). A higher drug concentration in the blood suggested better systemic absorption of ethosomes. The optimized formula has a Tmax of 4.0±0.08h and 73.38±1.37 of Cmax. The AMN ethosomes were found to be more stable when stored at 4 °C.

Conclusion: The current study suggests that ethosomal vesicles may improve transdermal dispersion without causing skin irritation. Agomelatine-loaded ethosome has the potential to be one of the most important transdermal application techniques for the treatment of depression.

TRANSETHOSOMES FOR ENHANCED TRANSDERMAL DELIVERY OF METHOTREXATE AGAINST RHEUMATOID ARTHRITIS: FORMULATION, OPTIMISATION AND CHARACTERISATION

2024-06-13T15:42:01+0530

Objective: The study aimed to develop and optimise Methotrexate (MTX)-loaded Transethosomal Film-Forming Gel (TE FFG) for transdermal delivery to treat rheumatoid arthritis while alleviating the side associated with oral administration.

Methods: The Transethosomes (TE) were prepared using the thin film hydration technique and incorporated into an FFG using chitosan. The Box-Behnken Design method was used to analyse the influence of independent variables such as the concentration of soya lecithin, surfactant, and ethanol on parameters including vesicle size, PDI (Polydispersity Index), zeta potential, and entrapment efficiency. The optimised transethosomal suspension was incorporated into the FFG using 3% chitosan and other excipients. In vitro drug release and ex vivo skin permeation of FFG were performed using Franz diffusion cells.

Results: The vesicle size, PDI, zeta potential and entrapment efficiency of the optimised formulation of TE were 110.3 nm, 0.352,-14.4 mV and 49.36%, respectively. The Transmission Electron Microscopy (TEM) image showed that the vesicles were uniform and spherical. The in vitro drug release study was higher for Conventional (CL) FFG) than TE FFG and the drug release mechanism was fitted into the Higuchi model. The permeation was higher for TE FFG, with the steady-state flux being 1.55 times greater than the CL FFG. The skin irritation test on Wistar rats revealed no indication of irritation on the skin. The histopathology examination showed a significant reduction in the inflammatory cells in the treated group.

Conclusion: Therefore, the results concluded that the formulated MTX-loaded TE FFG could be a potentially promising substitute for the oral delivery of methotrexate

OPTIMIZATION OF PROCESS PARAMETERS FOR ENHANCING THE SKIN PERMEATION EFFICIENCY OF NISOLDIPINE LOADED ULTRA DEFORMABLE VESICLES IN TRANSDERMAL PATCHES

2024-07-09T22:54:58+0530

Objective: The study aimed to address the limitations of oral delivery and enhance the bioavailability of nisoldipine (NSD) through the development of transferosomal transdermal patches containing ultra-deformable transferosomes.

Methods: NSD, known for its low oral bioavailability and adverse effects, was encapsulated in transferosomes using a thin film hydration method. 17 formulations were made using Box Behnken Design, varying Dipalmitoylphosphatidylcholine (DPPC), span-80, and stirring speed, and were evaluated for vesicle size, Polydispersity Index (PDI), and Entrapment Efficiency (EE%). The optimal formulation, selected based on these parameters, was combined into Transdermal Patches (TPs). The patches underwent extensive testing for physicochemical properties, in vitro and ex-vivo permeation, and skin irritancy.

Results: The results showed transferosomes with Vesicle Sizes (VS) ranging from 124±2.25 to 400±1.55 nm and EE% from 52.88±0.23 to 90.01±1.58%, with Zeta Potentials (ZP) between-48 to-20 mV. The patch thickness (0.66±0.02 mm) and weight per square inch (382.1±1.69 mg) showed consistent manufacturing, while the Water Vapor Transmission Rate (WVT) (1.54±0.01g/m²/24h), low moisture content (1.07±0.01%), and regulated moisture absorption (3.78±0.01%) maintained formulation stability. In vitro and ex-vivo permeation indicated superior drug permeation for transferosomal patches (NP) compared to plain nisoldipine patches (NP-N), with permeation directly proportional to PEG-400 concentration. Additionally, the transferosomal patches were found to be free from skin irritation.

Conclusion: The optimized Niosoldipine transferosomal patch (NP-3) composition displays good folding endurance (FE) 97.67±0.47, required for transdermal systems, and successfully allows drug permeation (DP) at 86.39±2.64% in a short timescale. Hence, the study concludes that transferosomal patches of NSD offer a promising approach for effective transdermal delivery, potentially improving hypertension management by providing a controlled and prolonged drug release.

NOVEL HYBRIDS OF QUINOLINE LINKED PYRIMIDINE DERIVATIVES AS CYCLOOXYGENASE INHIBITORS: MOLECULAR DOCKING, ADMET STUDY, AND MD SIMULATION

2024-07-10T11:53:15+0530

Objective: Finding novel anti-inflammatory compounds is a crucial sector of research despite the significant advances this field has made. Inefficiency and unfavorable side effects are indeed potential drawbacks of conventional therapy utilizing steroidal or nonsteroidal drugs. This study aims to screen the designed quinoline-linked pyrimidine derivatives as Cyclooxygenase (COX) inhibitors.

Methods: In the present study, we assessed the binding interactions of designed quinoline-linked pyrimidine derivatives with COX enzymes using a molecular docking approach. Using Molecular Dynamics (MD) simulations, the compound’s behavior was further investigated and its stability and conformational dynamics were demonstrated. Schrödinger's QikProp program was utilized to analyze the Absorption, Distribution, Metabolism, and Excretion (ADME) properties and toxicity properties were further investigated using Osiris Property Explorer. Additionally, the protein-ligand complexes' binding free energy has been ascertained using the Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) approach, which offered crucial information regarding the strength of their interactions.

Results: The designed quinoline-linked pyrimidine derivatives fulfilled the Lipinski Rule of Five and had physicochemical characteristics within acceptable ranges, better ADME properties, and were non-toxic. Among the designed compounds, QPDU1 and QPDT6 showed correspondingly good docking scores for COX-1 and COX-2. QPDT6 was additionally analyzed by MD simulation studies to thoroughly examine the interaction between protein and ligand and their stability.

Conclusion: The proposed compounds exhibit strong binding affinities to COX enzymes, stable interactions in MD simulations, and favorable drug-like features. These results support the need for more research and development of these substances as possible anti-inflammatory drugs.

THE CHOICE OF COMPONENTS AND THE IMPACT OF SURFACTANTS AND CO-SURFACTANTS ON EPLERENONE NANOEMULSION SYNTHESIS FOR GEL-BASED TRANSDERMAL APPLICATION

2024-07-12T19:16:54+0530

Objective: This research aims to establish an efficient methodology for selecting nanoemulsion components to synthesize eplerenone nanoemulsion for gel-based transdermal applications.

Methods: The chemical compatibility study of eplerenone was investigated by FTIR, DSC, and solubility in oils, surfactants, and co-surfactants as the criteria for choice. We used visual appraisal and grading to assess the effectiveness of emulsification. Various excipients were tested depending on solubility. The final appearance, dispersibility, and ease of emulsification were used to visually assess the degree of self-emulsification of oil and emulsifier in a 1:3 mass ratio. Co-surfactants were assessed by mixing particular emulsifiers in a 2:1 (w/w) ratio with co-surfactants, and the oily component was added at a 1:3 (w/w) ratio to evaluate Smix's emulsification potential. A central composite design synthesized, evaluated, and optimized eplerenone nanoemulsions. Optimized nanoemulsions were characterized after a thermodynamic stability study for droplet size, ζ potential, viscosity, refractive index, pH measurements, and TEM. All the selected formulations were found to be stable, and the droplet size was found to be<110 nm.

Results: Eplerenone was chemically compatible, and its maximum solubility was 171.3±0.92 and 169.3±2.22 in Kollicream^®OA and Paceol, respectively. The evidence impressively found that Tween 20 and Kolliphor^®EL were discovered as active emulsifiers, and Transcutol^®P was revealed to be a co-surfactant. Outcomes showed that the emulsification efficacy of Kolliphor^®EL (3% w/w) was able to emulsify Kollicream^®OA (1% w/w), and Paceol failed. As well, Smix [Kolliphor^®EL (2% w/w) and Transcutol^®P (1% w/w)] were able to emulsify Kollicream^®OA (1% w/w).

Conclusion: The main conclusion from this work is the application of a visual appraisal and grading system to assess the final appearance, dispersibility, and ease of emulsification to eradicate the toxicity and irritation that nanoemulsions can cause. Optimised nanoemulsions can further formulate eplerenone's nanoemulsion gel for transdermal application.

SAMBILOTO LEAF NANOEMULSION AS A PHOTOPROTECTIVE AGENT: OPTIMIZATION OF TWEEN 20 AND PEG-400 CONCENTRATION USING THE REGULAR TWO-LEVEL FACTORIAL DESIGN

2024-07-17T11:38:03+0530

Objective: This study aims to determine the optimum concentration of Tween 20 and Polyethylene Glycol 400 (PEG-400) in Sambiloto leaf extract nanoemulsion.

Methods: The formula of sambiloto leaf nanoemulsion was developed using the regular two-level factorial design based on responses of pH values, density, viscosity, and transmittance percentage. The optimum formula was tested for stability and photoprotective activity by determining the Sun Protection Factor (SPF) value and antioxidant activity.

Results: Sambiloto leaf extract contains andrographolide at 3.397%. The optimum formula for nanoemulsion preparations was obtained at 10% of tween 20 and 10% of PEG-400. The optimum nanoemulsion had a distinctive green extract aroma, a transmittance percentage of 86.7±0.170, a globule size of 130.43±54.056 nm, a polydispersity index of 0.318±0.043, and a zeta potential of-26.5±0.544 mV. The optimum formula's photoprotective activity resulted in an SPF value of 42.944±0.026 and an IC₅₀ of 103.611±1.085 ppm. There was no significant change in pH or transmittance percentage based on the stability test (p<0.05).

Conclusion: The results show that the optimum formula of sambiloto leaf nanoemulsion could be a photoprotective agent that is also stable.

BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR THE DETERMINATION OF ASCIMINIB ANTICANCER DRUG IN BIOLOGICAL MATRICES BY LC–ESI-MS/MS

2024-07-25T11:46:40+0530

Objective: A unique liquid chromatography-mass spectrometry technique is essential for determining the concentration of asciminib in biological matrices, and its development is of the utmost importance.

Methods: The samples that were processed were separated using a Reversed Phase-Phenomenex (100 mm x 4.6 mm, 5 µm) C18 analytical column. The column was equipped with an isocratic moveable phase that consisted of 0.1% (v/v) HCOOH and acetonitrile at a ratio of 18:82% (v/v). The flow rate of the phase was 0.70 ml/min. For asciminib, the multiple reaction monitoring mode was used at m/z 450.23/257.3, while for canagliflozin, it was used at m/z 445.13/267.31.

Results: With a correlation coefficient of 0.9998, the method was linear for asciminib throughout the concentration range of 1.0-2100.00 ng/ml. Each day's accuracy percentage relative standard deviation was within 5.74%. For analytes at the low-quality control level, the mean matrix factors ranged from 96.34 to 104.85% with a % Coefficient of Variance (CV) of 4.21; at the high-quality control level, the range was from 94.62 to 103.88% with a %CV of 3.67.

Conclusion: The method that has been developed has the potential to be used to examine the pharmacokinetics and toxicokinetics of asciminib in various biological samples for both forensic and clinical purposes.

FABRICATION AND CHARACTERIZATION OF DISSOLVING MICRONEEDLE PATCH USING 3D PRINTED MASTER

2024-08-14T15:48:17+0530

Objective: The purpose of this study was to fabricate a dissolving microneedle patch using a 3D-printed master and characterize it using various techniques.

Methods: Dissolving microneedle patches were developed using Computer-Aided Design (CAD) software and 3D printing. Polydimethylsiloxane (PDMS) reverse molds were cast from the 3D-printed masters and filled with a solution of 20% Chitosan Oligosaccharide (COS) and 20% Polyvinyl Alcohol (PVA). The patches were dried at room temperature and characterized using Scanning Electron Microscopy (SEM), Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), X-ray diffraction (XRD), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and in vitro skin penetration studies.

Results: Optical microscopy and SEM images showed the formation of a uniform microneedle. The peak at 1248 cm⁻¹ in the ATR-FTIR spectrum indicates the formation of cross-links between certain PVA radical groups and COS. XRD revealed that both polymers blended well and showed partial crystallinity, with peaks at 2θ = 11.39°, 2θ = 20°, and 2θ = 41°. DSC and TGA analyses revealed that the blend could withstand high temperatures with good stability at temperatures up to 200 °C. In vitro skin penetration studies confirmed that microneedles could successfully penetrate the skin, indicating their potential for effective transdermal drug delivery.

Conclusion: This study demonstrated that COS/PVA dissolving microneedles fabricated using 3D printing and micro-molding have significant potential for transdermal drug delivery.

DESIGN, SYNTHESIS, IN SILICO STUDIES, AND PHARMACOLOGICAL EVALUATION OF 5-ARYL-4-(CHLOROACETYLAMINO)-3-MERCAPTO-1,2,4-TRIAZOLE DERIVATIVES AS ANTICONVULSANT AGENTS

2024-08-29T13:50:24+0530

Objective: In this study, we reported the synthesis of a novel series of 5-aryl-4(chloroacetylamino)-3-mercapto-1, 2,4-triazoles.

Methods: These compounds were synthesized to screen for anticonvulsant effects in a Maximal Electroshock Seizure (MES) model and a Subcutaneous Pentylenetetrazole (sc‐PTZ) seizure model in rats. Furthermore, molecular docking studies with gamma-aminobutyric acid and in silico ADME prediction were carried out to determine interactions of these compounds with Benzodiazepine (BZD) receptors and their similarity with standard drugs. The rotarod test was used to evaluate neurotoxicity.

Results: 08 out of 40 compounds exhibited neurotoxicity at the maximum tested dose. Most of the compounds showed anti‐MES effects without any signs of neurological deficit. All the tested compounds significantly reduced seizures induced by PTZ compared to the control group. Carbamazepine and phenytoin were used as positive controls for anticonvulsant effects. Compounds 3d, 3h (a diphenylamine derivative of 5-aryl-4(chloroacetylamino)-3-mercapto-1,2,4-triazole), and 4a (a piperidinyl derivative of 5-aryl-4(chloroacetylamino)-3-mercapto-1,2,4-triazole) exhibited greater safety than phenytoin and carbamazepine in terms of neurotoxicity. The docking scores for the identified compounds 3d, 3h and 4a was 6.5133; 6.6558 and 5.6524, respectively. Nearly all the compounds (90%) demonstrated decreased locomotor activity.

Conclusion: It is gratifying that the compounds with higher hydrophobicity showed better performance in the seizure models. Many triazole derivatives holding a suitable aryl or alkyl group gave a better anticonvulsant activity in their analogs.

SYNERGISTIC EFFECT LUNG CANCER THERAPY: CO-DELIVERY OF QUERCETIN AND CISPLATIN VIA EUDRAGIT L-100 NANOPARTICLES IN VITRO

2024-08-25T14:04:24+0530

Objective: This study aims to investigate the potential of Eudragit L-100 nanoparticles for the co-delivery of quercetin and cisplatin to lung cancer cells, seeking to exploit the synergistic effects of the two drugs while overcoming their individual limitations.

Methods: We investigate the synergistic effect of co-delivering quercetin and cisplatin using Eudragit L-100 nanoparticles for lung cancer therapy. The nanoparticles were synthesized using the nanoprecipitation method, where Eudragit L-100 was dissolved in an organic solvent, followed by the incorporation of quercetin and cisplatin. The resultant nanoparticles were characterized for size, zeta potential, drug loading efficiency, and morphology using techniques such as Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM).

Results: The co-loaded Quercetin-Cisplatin Nanoparticles (Qu-Cis)-NPs formulation had a mean particle size of 475±4.77 nm. Polydispersion index of 0.266±0.093 and zeta potential was-24.03±0.89 mV. The in vitro cytotoxicity was assessed using normal cell and lung cancer cell lines in vitro studies showed that the developed nanoparticles significantly increased cancer cell mortality compared to individual drug treatments. The combination (Qu-Cis)-NPs showed more cytotoxicity on the Non-Small Lung Cancer Cell Line (NCI-H460) cancer cell line after 48 h of incubation compared to Qu loaded-NPs and Cis loaded-NPs, particularly at a concentration of 1 mg/ml. The combination showed no cytotoxicity effect on normal Human Lung fibroblast cell Lines (CCD-19 lu) cells at all concentrations after 24 h, but showed cytotoxicity effects at concentrations (0.125, 0.25, 0.5, and 1.0) mg/ml after 48 h.

Conclusion: The Eudragit L-100 nanoparticle system for co-delivering quercetin and cisplatin showed a promising synergistic effect in lung cancer treatment. It effectively addresses the solubility and toxicity issues of both drugs, offering a potentially more effective treatment option that merits further clinical investigation.

FORMULATION AND EVALUATION OF LULICONAZOLE NANOEMULGEL USING BOX-BEHNKEN DESIGN APPROACH

2024-05-21T15:11:38+0530

Objective: The present study was aimed to develop and assess a Luliconazole-loaded nano emulgel for topical application.

Methods: Nanoemulsion of Luliconazole was prepared by ultrasonication method. A pseudo-ternary phase diagram was constructed to determine the ideal ratio of oil and the surfactant/co-surfactant mixture for nanoemulsion preparation. The Box Behnken statistical design was utilized to optimize the nanoemulsion. The optimized batch of nanoemulsion was incorporated into the 1% Carbopol gel as nanoemulgel. It was evaluated for various parameters like globule size, zeta potential, pH, spreadability, viscosity, drug content, drug release, ex vivo permeation study, in vivo animal skin irritation study, and histopathology studies.

Results: The optimized formulation showed a globule size of 130.5 nm and entrapment efficiency of 80% and the values were found to be within±5% of predicted values, indicating the suggested statistical model was significant at 95% of confidence interval. The zeta potential of the formulation was found to be-22.1 mV, indicating enhanced stability of the formulation. Transmission Electron Microscopy (TEM) images revealed that the formulation had a smooth surface texture with a mean globule size meeting the nanoscale size range. The drug release study demonstrated a sustained release pattern for the formulation, with a maximum release of 74.93±0.8% over 8 h. The formulated gel exhibited appreciable ex vivo permeability. An in vivo skin irritation test on Wister rats showed no signs of skin irritation from the formulation. The histopathological examination further confirmed that the formulation was dermatologically safe, exhibiting no toxicity or irritation.

Conclusion: The results of the present study concluded that Luliconazole-loaded nanoemulgel could be a potential topical drug delivery approach for the management of fungal infections.

DEVELOPMENT OF GABAPENTIN-LOADED SOLID LIPID NANOPARTICLE FOR ALLEVIATING SEIZURE ACTIVITY IN PICROTOXIN AND BICUCULLINE-INDUCED RATS

2024-05-17T12:49:35+0530

Objective: The current research aimed to prepare gabapentin-loaded Solid Lipid Nanoparticles (SLN) for alleviating seizure activity in picrotoxin and bicuculline-induced Wistar rats.

Methods: Gabapentin-loaded SLNs were formulated using a Box-Behnken experimental design with three-level three-factor consisting of 17 experimental runs by micro-emulsification. Three independent parameters were considered in this study, namely sodium glyceryl tripalmitate (A), RPM (B), and Poloxamer-188 (C). Particle size, drug release, and Encapsulation Efficiency (EE) as dependent variables. The formulation was evaluated for drug release, EE, Attenuated Total Reflection (ATR), Differential Scanning Calorimetry (DSC), X-ray diffraction (XRD), surface morphology, particle size, zeta potential, in vivo anti-convulsion study.

Results: The data collected during the experiment includes the measurements of EE (Encapsulation Efficiency), drug release at the 12^th h, and particle size. It was reported that formulations containing a high concentration of Glyceryl tripalmitate (50%) had a high Encapsulation Efficiency (EE). The in vitro release results indicate that F17 demonstrated a maximum drug concentration of 99.99% within a 12 h. The optimization process was conducted using mathematical and graphical methods. From ATR spectra, it was found that there are no such major interactions between gabapentin and excipients. A significant endothermal peak was seen in the DSC investigation at 208.81 °C. X-ray diffraction revealed that gabapentin was present in the crystalline form. Drug crystals and SLN were seen to be dispersed and scattered from Scanning Electron Microscope (SEM). The optimized formulation's particle size was found to be 203.4 nm, the Polydispersity Index (PI) of 0.426, and the zeta value of 16.5 mV; indicating stability. Following a lethal and chronic dosage of picrotoxin, the gabapentin-SLN exhibited a higher anticonvulsant efficacy, according to in vivo research on rats (p<0.05).

Conclusion: Compared to the Bicuculline model, the optimized SLN demonstrated superior outcomes regarding seizure initiation in the Picrotoxin-induced convulsion.

ADVANCING TOPICAL POSACONAZOLE DELIVERY: BOX BEHNKEN DESIGN MICROSPONGE HYDROGEL OPTIMIZATION AND EXTENSIVE IN VIVO INVESTIGATION

2024-04-18T18:50:13+0530

Objective: The primary aim of this study was to develop a novel hydrogel formulation containing Posaconazole (PCZ) encapsulated within microsponges. Furthermore, the study aimed to assess the permeation properties of this formulation in vivo using a mouse model.

Methods: To achieve this aim, a series of seventeen trials were conducted using the Box Behnken Design methodology. These trials were designed to optimize the production of PCZ Microsponges (PCZ MS), which were subsequently incorporated into a hydrogel matrix. Skin permeation studies were then performed to evaluate the ability of the PCZ microsponge-based hydrogel to deliver the drug across the skin barrier. These studies involved comparison with a standard hydrogel formulation lacking microsponges.

Results: This study assessed the efficacy of microsponge gel formulation PM-3 for drug entrapment, yield, and sustained release compared to a conventional gel. PM-3 displayed the highest entrapment efficiency of 98.5% and a yield of 95.62%, indicating a direct correlation with the 1:1 drug-polymer ratio. Moreover, PM-3 exhibited sustained drug release over 12 h, releasing 83.82% of PCZ compared to 65.31% with the normal gel, suggesting its potential for prolonged therapeutic action. These findings underscore the promise of microsponge-based hydrogels, like PM-3, in enhancing therapeutic outcomes through sustained drug release, warranting further exploration for clinical applications.

Conclusion: The findings of this study highlight the promising potential of microsponge-based hydrogels as effective carriers for localized drug delivery, particularly in the context of treating skin fungal infections.

SUBLIMATION-BASED CUTTING-EDGE TECHNOLOGY (SUSTAINABLE DEVELOPMENT GOALS 9 and 15) TO DEVELOP CURCUMIN NANOPARTICLES BY SOLVENT-FREE GREEN CHEMISTRY METHOD FOR THEIR ANTIOXIDANT AND ANTICANCER ACTIVITY

2024-05-11T19:22:49+0530

Objective: This research aimed to develop a new, cost-effective, solvent/surfactant/supercritical carbon dioxide-free, sublimation-based method to prepare curcumin nanoparticles. The research objective was to meet Sustainable Development Goals (SDG-3,9 and 15). The problem of poor absorption of curcumin is sorted out by micro or nanonization, solid dispersion, solid solution, β-cyclodextrin complexation, micelle formation, and solution-enhanced dispersion by supercritical carbon dioxide.

Methods: The curcumin, mixed with menthol, was allowed to melt at 29 °C and placed under vacuum for 6 H (h). The menthol sublimates and leaves the curcumin particles as residue. The residual curcumin particles were characterised, and stability studies were also performed.

Results: The curcumin nanoparticles were stable, in the nano-size range (10-300 nm); Fourier Transform Infrared Spectroscopy (FTIR) showed the presence of CH₃ and CH₂ bending, aromatic C=C and C=O stretching, aromatic CC and OH stretching, aliphatic C-H bending, aromatic-OH bending with both pure curcumin and curcumin nanoparticles, that no change in bonds and groups, and differential scanning calorimetry (DSC) showed the temperature (T) =162.03, 185.64 and peak maximum is 177.986 for pure curcumin while T=164.43, 185.68 and peak maximum is 177.784 for curcumin nanoparticles that indicated compatibility between curcumin and menthol. The curcumin nanoparticles showed improved solubility, dissolution, and antioxidant activity by calculating Inhibitory Concentration₅₀ (IC₅₀) value 114.51 and in vitro cytotoxicity (IC₅₀=165.6±0.084 µg/ml) of curcumin nanoparticles against MCF-7, a human breast cancer cell line with estrogen, progesterone, and glucocorticoid receptors.

Conclusion: It concluded that the sublimation technique can used to prepare the nanoparticles of drugs or might be for thermo-labile drugs.

SOLID LIPID NANOPARTICLES OF FENUGREEK SEED EXTRACT IN A DERMATOLOGICAL BASE FOR ALOPECIA: AN IN VIVO STUDY

2024-05-02T10:44:29+0530

Objective: The objective of the study was to investigate the potential of Solid Lipid Nanoparticles (SLN) of Fenugreek Seed Extract (FSE) in a dermatological base for its hair growth activity in alopecia

Methods: The optimized SLN formulation of FSE was loaded into neutralized Carbopol 934 gel, and its hair growth efficacy was studied in Wistar rats in terms of hair density and length. Alopecia was induced in the rats by administering cyclophosphamide at a dose of 40 mg/kg for three days. The formulations were applied to the skin for twenty-one days following the induction of the disease. The hair growth in FSE-SLN gel-treated groups were compared with disease control and other treatment groups using qualitative and quantitative assessments.

Results: FSE-SLN gel reduced the hair growth completion time comparable to that of the standard (p<0.01). The increase in hair length was significantly (p<0.01) greater in FSE SLN groups compared to groups treated with conventional gels, oils, and marketed formulations, demonstrating the superior hair growth efficacy of the developed FSE SLN.

Conclusion: SLNs can enhance the penetration of extract into the skin (stratum corneum) compared to oil and gels, thereby increasing treatment efficiency, targeting the epidermis, and reducing systemic absorption and related side effects. Consequently, the developed nanoformulation can be a substitute for in vivo hair growth activity.

POTENTIALITY OF PROTEIN HYDROLYSATE FROM ANADARA GRANOSA AS NUTRACEUTICAL AGENT: ANTIOXIDANT AND ANTIBACTERIAL ACTIVITIES

2024-05-17T13:26:53+0530

Objective: This study aims to extract protein hydrolysate from Anadara granosa and assess its impact on protein solubility, antioxidant, and antibacterial activities.

Methods: Several methods were used, including the isolation of enzyme bromelain, protein extraction from A. granosa, and the breakdown of protein using trypsin and bromelain. Together with its protein solubility, antioxidant activity (IC50) against free radicals (DPPH), the protein hydrolysate's antibacterial activity (MIC and inhibition zone) against Staphylococcus aureus and Escherichia coli was evaluated.

Results: With a molecular weight of 10 kDa and an IC50 of 83.81 mg/ml, the trypsin protein hydrolysate fraction showed remarkable antioxidant activity after 5 h of incubation. At a dosage of just 0.25 mg/ml, the A. granosa protein and its corresponding hydrolysate had inhibitory zones against S. aureus and E. coli that were comparable to those observed in samples treated with amoxicillin. Using trypsin as an enzyme for 3 or 5 h produced the strongest hydrolyzed product. The trypsin hydrolysate was better than the bromelain hydrolysate because of its antioxidant and antibacterial activities.

Conclusion: Based on the results, antioxidant and antibacterial activities, and protein solubility were influenced by enzymatic hydrolysis.

DESIGN, OPTIMIZATION AND EVALUATION OF RANOLAZINE FAST-DISSOLVING FILMS EMPLOYING MANGO KERNEL STARCH AS A NEW NATURAL SUPERDISINTEGRANT

2024-05-22T18:11:09+0530

Objective: The BCS class II cardiovascular medication, Ranolazine (RZN), is characterized by limited solubility and inadequate oral absorption. The objective of the current research is to develop a natural superdisintegrant in the formulation of Fast-Dissolving Films (FDFs) of Cardio Vascular Drug (CVD) RZN to enhance its dissolution rate, solubility, absorption, and therapeutic action.

Methods: Mango Kernel Starch (MKS) is isolated by grinding the kernels, forming a slurry with water, filtering, and using repeated centrifugation and washing to purify the starch, which is then dried. The obtained starch is collected. Along with obtained natural superdisintegrant MKS, Maltodextrin (MDX) and Sodium Starch Glycolate (SSG) were also utilized in the fabrication of FDFs containing RZN via the solvent casting technique. A total of eight formulations (RF1 to RF8) were developed employing a 2³ factorial design, using the natural superdisintegrant alone at a concentration of 5% and in combination with other superdisintegrants.

Results: The prepared MKS was found to be free-flowing, fine, amorphous, insoluble in organic solvents, and exhibiting 0.17% solubility in water with a swelling index of 89.95%, indicating superdisintegrant properties. Fourier-transform infrared spectroscopy (FTIR) studies and Differential scanning calorimetry (DSC) analysis indicated that there was no drug-excipient interaction. The films prepared with a 5% concentration of the MKS showed good physical properties and resulted in an increased drug dissolution rate, with 99.78 % of the drug dissolved within 10 min, along with the lowest disintegration time of 13.45 sec.

Conclusion: The research successfully isolated a new superdisintegrant, MKS and formulated FDFs of the poorly water-soluble drug RZN. The MKS was found to be an effective superdisintegrant with no drug interactions, producing films with good physical and mechanical properties, increasing the drug dissolution rate, and providing rapid disintegration with improved relative bioavailability.

FORMULATION, CHARACTERIZATION AND OPTIMIZATION OF PLGA-CHITOSAN-LOADED FATTY ACID SCAFFOLDS FOR THE TREATMENT OF DIABETIC WOUNDS

2024-05-23T17:30:39+0530

Objective: The objective of the current research to formulate Eicosapentanoic Acid/Decosahexanoic Acid (EPA/DHA)incorporated into Chitosan (CS)and Poly-Lactic-Glycolic Acid (PLGA), nanoparticles composite scaffolds to the accelerated diabetic wound healing. The main focus of this present research is to evaluate and develop the chitosan–PLGA biodegradable polymer scaffolds loaded with long-chain omega-3 Polyunsaturated Fatty Acids (PUFA’s) (EPA/DHA).

Methods: Nano scaffolds were prepared by solvent evaporation method loaded with CS-PLGA, EPA and DHA to treat diabetic wounds at targeted site as pharmacotherapeutically. Upon investigation, the developed biodegradable crosslinked scaffold possesses matrix degradation, optimal porosity, prolonged drug release action than the non-cross linked scaffold. The prepared formulation containing CS-PLGA loaded with EPA/DHA were formulated as nanoscaffold for wound topical applications was carried out by using freeze drying process.

Results: The prepared CS-PLGA nano scaffolds were optimized and evaluated for physicochemical properties, dynamic light scattering with a particle size of 248 nm and zeta of-24mVand Scanning Electron Microscopy (SEM) were found to be spherical. In addition, the optical properties of EPA/DHA and PLGA, along with CS, can be compared by examining their absorption and wavelength (nm) using UV-visible spectroscopy. The structural and functional groups of the prepared end products were characterized by Fourier-Transformed Infrared Spectroscopy (FT-IR) has shown good compatibility with excipients and nanoformulaton, in vitro drug release studies done by using dialysis bag membrane results find that first-order Higuchi model was followed showing 20% release in first 0.2 h. MTT(3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide) assay was carried out and it showed that both crosslinked and non-crosslinked scaffolds(110 and 120%) improved cell growth when compared to control (100%).

Conclusion: Finally, the results showed that the PLGA, CS nanoscaffolds containing 98% of PUFA’s (EPA/DHA) have increased in proinflammatory cytokines production at the particular wound site and thus accelerated healing activity, depending on the pre-clinical studies have trespassed, the therapeutic potential to penetrating at wound site. The optimized nanoformulation could be a better formulation for targeting and treatment of diabetic wounds at an optimal ratio.

PREPARATION, CHARACTERIZATION, AND IN VITRO EVALUATION OF GEL CONTAINING NANOPHYTO-PHOSPHOLIPID COMPLEX OF KOPASANDA LEAF EXTRACT (CHROMOLAENA ODORATA (L.) R. M. KING AND H. ROB)

2023-12-17T19:51:17+0530

Objective: This study aims to prepare, characterize, and in vitro evaluation of the gel containing nanophyto-phospholipid complex of kopasanda leaf extract.

Methods: Kopasanda dried leaf was extracted by extraction reflux method, followed by total phenolic content of extract measurement using Spectrophotometry UV-Vis method. The nanophyto-phospholipid complex was prepared using an antisolvent evaporation method with various ratios between extract and phospholipid of 1:1; 1:2; 1:3. The optimum ratio was evaluated by entrapment efficiency (%). The nanophyto-phospholipid complex formation was characterized by polydispersity index, particle size, Fourier Transform Infra-Red (FT-IR), and the Transmission Electron Microscope (TEM) method. The optimum nanophyto-phospholipid complex was formulated into gel preparation. The in vitro permeation study was performed to discover the influence of gel containing nanophyto-phospholipid complex compared with gel-containing extract without the nanophyto-phospholipid complex formation.

Results: Thetotal phenolic content of kopasanda leaf extract was 117.214±3.054 mg/GAE. The optimum ratio of kopasanda leaf extract and phospholipid was 1: 2 with entrapment efficiency (%), particle size, and polydispersity index equal to 99.897±0.001%, 130.1 nm and 0.394. The morphology of the nanophyto-phospholipid complex was spherical and the complex formation was confirmed by the FTIR spectrum. The permeation test showed that the gel containing nanophyto-phospholipid complex had better diffusion than the gel without the nanophyto-phospholipid complex formation.

Conclusion: The gel containing nanophyto-phospholipid complex formation exhibited the potential drug delivery system to increase the phenolic content permeation of kopasanda leaf extract.

DEVELOPMENT OF 1H-INDAZOLE DERIVATIVES AS ANTI-INFLAMMATORY AGENTS USING COMPUTATIONAL METHODS

2024-05-29T13:06:55+0530

Objective: Due to the rising prevalence of disorders linked to inflammation, there is a greater emphasis on the discovery and development of anti-inflammatory drugs, with a focus on producing new structural compounds.

Methods: In this research, molecular docking and Molecular Dynamics (MD) simulation study were carried out to evaluate the 1H-indazole analogs as potent anti-inflammatory agents.

Results: The compounds containing difluorophenyl, para-toulene and 4-methoxyphenyl group shows significant binding results (9.11, 8.80 and 8.46 kcal/mol respectively) when docked with Cyclooxygenase-2 (COX-2) enzyme 3NT1. The results of the MD simulation indicated that test compound BDF was relatively stable in the COX-2 enzymes active sites. The compound BDF-3NT1 demonstrated substantial affinities for binding with all of its aimed targets following a dynamic Molecular Mechanics with Generalized Born Surface Area (MM-GBSA) analysis.

Conclusion: In accordance to this study, newly developed 1H-indazole compounds have the potential for treating inflammation.

BOX-BEHNKEN DESIGN ASSISTED ECO-FRIENDLY RP-HPLC-PDA METHOD FOR THE QUANTIFICATION OF PACLITAXEL: APPLICATION TO EVALUATE THE SOLUBILITY OF PACLITAXEL-CYCLODEXTRIN COMPLEX

2024-06-03T17:03:32+0530

Objective: Paclitaxel (PTX) is one of the oldest chemotherapeutic agents for cancer treatment. However, PTX is a class IV drug under the Biopharmaceutical Classification System (BCS), and its oral administration is restricted due to its low bioavailability. Complexing PTX with Beta-Cyclodextrin (β-CD) is an option to overcome the low solubility and bioavailability. This study aims to optimize and develop an RP-HPLC analytical method for quantifying PTX from the fabricated β-CD complex.

Methods: The HPLC settings were optimized using Design-of-Experiments (DOE) software. The independent variables for the optimization process were buffer ratio, buffer pH, flow rate, and injection volume. The responses were Retention Time (RT), peak area, Tailing Factor (TF), and number of Theoretical Plates (TP) of PTX. The validated method was then used to measure the % entrapment from the PTX-β-CD complex.

Results: The developed and optimized RP-HPLC method was validated as per International Council for Harmonisation (ICH) Q2 (R1) guidelines. The developed method showed linearity R² = 0.999 with a 0.5-20 µg/ml range. The Limit of Detection (LOD) and Limit of Quantification (LOQ) were 95 and 125 ng/ml, respectively. The accuracy and precision for the developed method came under the acceptance criteria. The developed method was used to evaluate the enhancement of solubility of the prepared PTX-β-CD complex. The method was also used in the evaluation of % drug loading, % drug release and stability of the PTX-β-CD complex. The study clearly showed that the solubility of PTX increased from 0 to 1.14±0.53 µg/ml at pH 1.2 and 0 to 3.18±0.61 µg/ml at pH 6.8, respectively. The PTX-β-CD complex showed 73±3.75% drug release in 120 min at pH 1.2 and 87±3.51% at pH 6.8. The developed RP-HPLC method was found to be eco-friendly as per the Analytical Greenness (AGREE) metric approach and software analysis.

Conclusion: An eco-friendly RP-HPLC analytical method was successfully developed and optimized for the quantification of PTX from the PTX-β-CD complex.

IDENTIFYING POTENTIAL hENR INHIBITORS AGAINST PROSTATE CANCER EMPLOYING IN SILICO DRUG REPURPOSING APPROACH

2024-06-05T11:58:20+0530

Objective: This study employed an in silico drug repurposing strategy to identify potential human enoyl acyl carrier protein reductase (hENR) inhibitors.

Methods: The co-crystallized ligand triclosan was used as a reference standard. Initially, FDA-approved drugs from the Drug Bank database were docked against the hENR and compounds with appreciable binding affinities with the protein were shortlisted. The binding energy calculations, ADME analysis, and induced-fit docking results of shortlisted compounds led to the identification of two top hits, DB07676 and DB11399, which were further subjected to molecular dynamics simulation.

Results: Of 2,509 ligands docked via High Throughput Virtual Screening (HTVS), the top 250 were assessed with Standard Precision (SP) and the top 25 with Extra Precision (XP) mode. Thirteen compounds were selected based on interactions and XP scores, ranging from-15.245 to-10.031. Relative binding free energies of ligands DB07676 and DB11399 were-54.18 and-61.38 kcalmol^-1, respectively. ADME analysis confirmed that both ligands followed Lipinski's Rule, though DB11399 had a high log P, which could be addressed by adding polar groups. Induced Fit scores for DB07676 and DB11399 were-10.592 and-11.220, respectively. Molecular Dynamics simulations confirmed superior stability of these complexes with RMSD ranging from 1.2 to 3.5 Å for the protein and 1.7 to 5.2 Å for the ligand with DB07676-protein complex and 1.4 to 3.0 Å for the protein and 1.1 to 5.8 Å for the ligand with DB11399-protein complex.

Conclusion: Our final findings suggested that DB07676 and DB11399 could be potential lead compounds as hENR inhibitors.

DESIGN, SYNTHESIS, AND BIO PROFILING OF 2, 3-DIHYDROQUINAZOLIN-4(1H)-ONE DERIVATIVE AS TYPE II DIABETES AGENTS: A COMPREHENSIVE IN SILICO, IN VITRO, AND IN VIVO STUDY

2024-06-06T00:10:25+0530

Objective: Diabetes mellitus is a significant global health challenge, with Type 2 Diabetes Mellitus (T2DM) being a leading cause of mortality worldwide, demanding the need for effective interventions by developing innovative therapeutic strategies or novel antidiabetic agents. This study explores in silico, in vitro, and in vivo approaches to identify the most potent 2,3-Dihydroquinazolin-4(1H)-One derivative molecule with antidiabetic activity.
Methods: Eleven new derivatives were designed, studied in silico to identify the most promising compounds, synthesized, studied spectrally to describe them, and evaluated for both in vitro and in vivo investigations. Alpha amylase and alpha-glucosidase inhibitory activities were investigated in vitro. The endogenous suppression of glucose synthesis in Hepatoblastoma cell line 2(HepG2) cells and the in vitro glucose absorption assay on cultivated L6 cell lines were conducted. To assess the ability of the newly synthesized compounds to prevent diabetes, in vivo investigations were conducted on Streptozotocin (STZ)-induced diabetic rats and the effects on various biochemical parameters were identified.
Results: Leveraging computational methods, the QZ9 molecule was identified with stable interactions with key biomolecules associated with T2DM. Subsequent in vitro assays confirmed the inhibitory effects of QZ2, QZ8, and QZ9 on alpha-amylase and alpha-glucosidase activities, suggesting their potential as enzyme inhibitors. Additionally, QZ8 and QZ9 demonstrated enhanced glucose uptake and production inhibition in HepG2 cells, indicating their role in improving glucose homeostasis. In vitro, the top-ranked molecules QZ2, QZ8, and QZ9 were analyzed to validate the in silico findings and assess their potential as therapeutic agents for T2DM. The inhibition of α-amylase activity by QZ2, QZ8, and QZ9 was dose-dependent, with maximum inhibition observed at 1000 µg/ml: 57.33% for QZ2, 52.21% for QZ8, and 87.16% for QZ9. Similarly, α-glucosidase inhibition at 1000 µg/ml was 59.96% for QZ2, 53.50% for QZ8, and 81.51% for QZ9. Both QZ8 and QZ9 significantly increased glucose uptake and inhibited glucose production in HepG2 cells, with maximum glucose production inhibition at 100 µg/ml: 62.22% for QZ8 and 62.35% for QZ9. These findings suggest that QZ8 and QZ9 contribute to glucose homeostasis. QZ9 demonstrated superior enzyme inhibition compared to QZ2 and QZ8, with α-amylase and α-glucosidase inhibition up to 87.16% and 81.51%, respectively, at 1000 µg/ml. In vivo investigations in Diabetic rat models further confirmed the efficacy of these compounds by showing significant reductions in blood glucose levels. These results suggests the potentiality of QZ9 as a promising novel Antidiabetic agent.
Conclusion: Combining computational predictions with experimental validations, this integrated approach highlights the promise of 2,3-Dihydroquinazolin-4(1H)-One derivative QZ9 as a novel antidiabetic agent, warranting further investigation for clinical translation.

MUNTINGIA CALABURA SILVER NANOPARTICLES DETERIORATE OXIDATIVE IMPAIRMENT WITH POTENT ANTIBACTERIAL ACTIVITY

2024-06-06T15:58:31+0530

Objective: The current study exemplifies the synthesis of silver nanoparticles using Muntingia calabura L. (Mc-AgNP’s) fruit extract utilizing a green approach and testing the efficacy of synthesized NP’s.

Methods: The green synthesize approach was used to synthesis Mc-AgNP’s followed by characterization using Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Energy Dispersive X-ray Spectroscopy (EDX), and Field Emission Scanning Electron Microscopy (FESEM). Radical scavenging activity was assessed using DPPH, FRAP, and H₂0_2, followed by antibacterial activity.

Results: The characteristic features of synthesized Muntingia calabura silver nanoparticles (Mc-AgNP’s) were analyzed using FT-IR which particularizes different functional groups with a broadband at 3408 cm-1 representing hydroxyl (-OH) stretching a peak at 1593.27 cm-1 corresponds to C = O groups in amide whereas a dip at 1383 cm-1 represents C-N amine and C-O stretching of alcohol groups were found. The Crystallinity of synthesized Mc-AgNP’s exhibited face-centered cubic (fcc) crystalline structure and the bio-reduction of the silver ions in solution was monitored by Energy dispersive X-ray spectroscopy (EDX). The FESEM analysis indicates that Mc-AgNP’s were dispersed in the solution using micrographs and the size ranged from 10 to 60 nm. The synthesized Mc-AgNP’s efficiently scavenged free radicals in a dose-dependent manner with 69% for DPPH, 59.9% for FRAP, and 64% for H₂0₂ respectively. Further, the synthesized Mc-AgNP’s demonstrated a potent antimicrobial agent against tested bacterial and fungal strains with a maximum zone of inhibition observed in S. aureus, K. pneumonia, and P. vulgaris with 14.6, 13.8, and 12.4 mm. Similarly, antifungal activity with Trichoderma harzianum demonstrated the highest zone with 18 mm followed by Aspergillus oryzae with 7 mm.

Conclusion: These results highlight the interesting potential of synthesized Mc-AgNP’s as an effective source of bioactive compounds with potent antioxidant and antibacterial activity.

SYNERGISTIC POTENTIAL OF NIGELLA SATIVA L. AND TRIGONELLA FOENUM-GRAECUM: INTEGRATED NETWORK PHARMACOLOGY FOR DIABETIC WOUND HEALING

2024-06-07T13:31:12+0530

Objective: Diabetes Mellitus (DM) is a metabolic disorder marked by elevated blood glucose levels, and one of the issues linked to DM involves the development of Diabetic Wounds (DW). DW is susceptible to infection and develops into chronic wounds if not treated properly. This study aimed to investigate the network pharmacology of N. sativa L. and T. foenum-graecum, emphasizing on their potential as DW treatment candidates.

Methods: Various databases were used in this study, including PubChem, Dr. Duke's phytochemistry and Ethnobotany, and KNApSAcK Family. Swiss Target Prediction and Way2Drug PASS Online were utilized for biological activity and protein target prediction. The DW pathway's protein-protein interactions were examined with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Cards, and STRING databases. STRING was used to predict the metabolite's action. The relationship between metabolites and target proteins was predicted using STITCH, and Cytoscape was used to visualize the network.

Result: The results showed that ten active ingredients (five active ingredients in N. sativa L. and five active ingredients in T. foenoem-graecum) contributed to DW healing by affecting Tumor Necrosis Factor (TNF), Interleukin-1beta (IL1B), JUN, Caspase 3 (CASP3), Interleukin-6 (IL-6), Alpha Kinase Threonine-1 (AKT1), Vascular Endothelial Growth Factor-A (VEGFA), and Mitogen-Activated Protein Kinase 3 (MAPK3) genes. Furthermore, the ten active ingredients correlated with twenty-eight intracellular proteins, resulting in a mechanism involving eight DW signalling pathways.

Conclusion: Based on network pharmacology analysis, we determine that N. sativa L. and T. foenoem-graecum combination can potentially treat DW.

COMPUTATIONAL ANALYSIS, IN SILICO TOXICITY PREDICTION AND IN VITRO ANTIMICROBIAL EFFICACY OF ZINGIBER OFFICINALE ROSC. EXTRACT AGAINST PORPHYROMONAS GINGIVALIS

2024-06-09T21:30:29+0530

Objective: This study aimed to determine the molecular activity, toxicity prediction and in vitro antimicrobial efficacy of Zingiber officinale Rosc Extract.

Methods: The molecular docking method was used to evaluate the antibacterial activity of the main compounds in Zingiber officinale by examining their interaction with DNA Gyrase IIb and Topoisomerase II. Chemical toxicity analysis was conducted using pK-CSM, SwissADME, and Pro-Tox II methodologies. Zingiber officinale rhizome was extracted via maceration, and its phytochemical content was determined. An in vitro antibacterial study against P. gingivalis was performed by measuring the inhibition zone using digital slide calipers and the disk diffusion method.

Results: The in silico toxicity test of the main components from Zingiber officinale revealed that gingerol, shogaols, and paradols have predicted LD50 values of 250 mg/kg, 687 mg/kg, and 2580 mg/kg, respectively, placing them in toxicity classes 3, 4, and 5. Their average similarity is 100% for gingerol and shogaols, and 87.52% for paradols, with prediction accuracies of 100% and 70.97%. Molecular docking indicated that gingerol, shogaols, and paradols inhibit DNA gyrase B and Topoisomerase II, which are involved in bacterial regeneration. The inhibition zones for concentrations of 60%, 40%, 20%, and 10% averaged 22.87 mm, 18.5 mm, 14.5 mm, and 11.31 mm, respectively, with Minimum Inhibitory Concentration (MIC) values of 10% and Minimum Bactericidal Concentration (MBC) values of 40%, showing the highest inhibition zone at 60%.

Conclusion: Zingiber officinale rhizome extract showed growth inhibition activity of Porphyromonas gingivalis ATCC®33277™.

DEVELOPMENT, OPTIMIZATION AND ASSESSMENT OF NAPROXEN MICROSPONGES BY BOX-BEHNKEN DESIGN AS A TARGETTED AND CONTROLLED RELEASE DRUG DELIVERY

2024-06-12T22:51:40+0530

Objective: Due to weak physical, chemical stability and poor bioavailability of Naproxen conventional dosage form; the purpose of this work is to improve formulation stability, additionally to accomplish highest possible concentration of the drug in the blood by preparing Naproxen loaded microsponges.

Methods: Naproxen Microsponge (NM) was created utilising the quasi emulsion technique. In this process Ethyl Cellulose (EC) acts as a polymer, Poly Vinyl Alcohol (PVA) acts as the emulsifier, and Dichloromethane acts as the solvent. To investigate how changes in different formulation and processing parameters affect important product qualities, a Box Behnken Design (BBD) was used. Particle Size, Percentage Yield, and Entrapment Efficiency (%EE) were selected as response factors, whereas independent variables including EC quantity (X1), PVA concentration (X2), and Stirring Speed (X3) were selected as independent variables.

Results: The microsponges underwent thorough analysis using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FT-IR), X-Ray Diffraction (XRD), and Particle Size analysis. The evaluation included studying the morphology, drug loading, and in vitro drug release. The compatibility studies showed no chemical interactions between the drug and the polymers used. It was observed that the ratio of drug to polymer had a significant impact on drug content, EE and particle size. The SEM results revealed that the microsponges were spherical with a porous surface and had a mean particle size of 15.15 µm. The in vitro drug release studies demonstrated that the optimized Naproxen Microsponge Formulation (NMF2) achieved over 80% extended drug release by the end of 8 h, following the Corsmeyer Peppas Model.

Conclusion: The Naproxen loaded microspheres possessed a sustained release with improved bioavailability and better stability.