SMART CHITOSAN-BASED MICROBEAD FORMULATION FOR COLON-TARGETED DELIVERY OF LACTOFERRIN

LUQMAN OLAOYE; AZAD SADRADDIN; SHWANA BRAIM

doi:10.22159/ijap.2024v16i5.51185

Authors

LUQMAN OLAOYE Department of Chemistry and Forensic Science, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, United Kingdom https://orcid.org/0009-0000-5045-7584
AZAD SADRADDIN Department of Chemistry, Salahaddin University-Erbil, Kurdistan Region https://orcid.org/0000-0002-1054-7363
SHWANA BRAIM Department of Chemistry and Forensic Science, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, United Kingdom https://orcid.org/0000-0002-0019-8972

DOI:

https://doi.org/10.22159/ijap.2024v16i5.51185

Keywords:

Lactoferrin, Colorectal cancer, Chitosan, PEGMA-g-Cs, Smart formulation, Targeted delivery

Abstract

Objective: This study aims to develop a novel smart formulation based on dual-responsive Polyethylene Glycol Methacrylate-Grafted-Chitosan (PEGMA-g-Cs) copolymers for the controlled delivery of Lactoferrin. The goal is to enhance the bioavailability and therapeutic efficacy of Lactoferrin in treating colorectal cancer, addressing its rapid degradation in a highly acidic gastric environment.

Methods: Gold-coated Superparamagnetic Iron Oxide Nanoparticles (Au-SPIONs) were synthesized and loaded into PEGMA-g-Cs microspheres. Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Proton Nuclear Magnetic Resonance (HNMR), X-Ray Diffraction (XRD), Infrared Spectroscopy (IR), UV-visible spectrophotometry (UV-Vis), optical microscopy, and Dynamic Light Scattering (DLS) were used to characterise the synthesized materials. Drug loading and release studies of lactoferrin-loaded microbead formulations were conducted to evaluate encapsulation efficiency, loading capacity, and release profiles.

Results: The lactoferrin-loaded microbead formulations demonstrated excellent encapsulation efficiency and loading capacity. Specifically, Encapsulation Efficiency (EE) was 77% and Loading Capacity (LC) was 4.99% for the homogenizer batch, while the magnetic stirring batch achieved 86% EE and 3.12% LC. The formulation exhibited minimal release (<20%) in Simulated Gastric Fluid (SGF) and almost complete release in Simulated Colonic Fluid (SCF). The 3-[4,5-Dimethylthiazol-2-Yl]-2,5-Diphenyl Tetrazolium Bromide (MTT) cell cytotoxicity assay in human CaCo-2 colon cancer cells revealed a significant reduction in cell proliferation following treatment with the new formulations.

Conclusion: The findings suggest that the new formulation can be a promising approach for the targeted delivery of Lactoferrin, thereby improving the efficacy of colorectal cancer treatment by enhancing the bioavailability of lactoferrin.

Downloads

Download data is not yet available.

References

Alaryani FS, Turki Alrdahe SS. A review of treatment, risk factors, and incidence of colorectal cancer. Int J App Pharm. 2022;14(1):1-6. doi: 10.22159/ijap.2022v14i1.42820.

Muhammed RA, Mohammed S, Visht S, Yassen AO. A review on development of colon targeted drug delivery system. Int J App Pharm. 2024;16(2):12-27. doi: 10.22159/ijap.2024v16i2.49293.

Dhas SK, Deshmukh G. Formulation and evaluation of meloxicam microspheres for colon targeted drug delivery. Asian J Pharm Clin Res. 2021;14(8):45-51. doi: 10.22159/ajpcr.2021.v14i8.38482.

Patil AS, Puri R, Wakure BS. A review on lactoferrin principle constituent of bovine colostrum: in COVID19. Int J Curr Pharm Sci. 2022;14(3):1-8. doi: 10.22159/ijcpr.2022v14i3.1984.

Khan AR, Sadiq IZ, Abdullahi LI, Danlami D, Taneja P. Chemoprotective role of bovine lactoferricin against 7,12 dimethylbenz[a]anthracene induced skin cancer in female swiss albino mice. Int J Pharm Pharm Sci. 2016;8(8):215-22.

Mohd KS, Hassan MA, Azemin WA, Dharmaraj S. A review of potential anticancers from antimicrobial peptides. Int J Pharm Pharm Sci. 2015;7:19-26.

Coccolini C, Berselli E, Blanco Llamero C, Fathi F, Oliveira MB, Krambeck K. Biomedical and nutritional applications of lactoferrin. Int J Pept Res Ther. 2023;29(5):71. doi: 10.1007/s10989-023-10541-2.

Shini VS, Udayarajan CT, Nisha P. A comprehensive review on lactoferrin: a natural multifunctional glycoprotein. Food Funct. 2022;13(23):11954-72. doi: 10.1039/d2fo02371g, PMID 36383056.

Cutone A, Ianiro G, Lepanto MS, Rosa L, Valenti P, Bonaccorsi di Patti MC. Lactoferrin in the prevention and treatment of intestinal inflammatory pathologies associated with colorectal cancer development. Cancers. 2020;12(12):3806. doi: 10.3390/cancers12123806, PMID 33348646.

Pan S, Weng H, Hu G, Wang S, Zhao T, Yao X. Lactoferrin may inhibit the development of cancer via its immunostimulatory and immunomodulatory activities (review). Int J Oncol. 2021;59(5):85. doi: 10.3892/ijo.2021.5265, PMID 34533200.

Kruzel ML, Zimecki M, Actor JK. Lactoferrin in a context of inflammation-induced pathology. Front Immunol. 2017;8:1438. doi: 10.3389/fimmu.2017.01438, PMID 29163511.

Abd El-Hack ME, Abdelnour SA, Kamal M, Khafaga AF, Shakoori AM, Bagadood RM. Lactoferrin: antimicrobial impacts, genomic guardian, therapeutic uses and clinical significance for humans and animals. Biomed Pharmacother. 2023;164:114967. doi: 10.1016/j.biopha.2023.114967, PMID 37290189.

Kowalczyk P, Kaczynska K, Kleczkowska P, Bukowska Osko I, Kramkowski K, Sulejczak D. The lactoferrin phenomenon-a miracle molecule. Molecules. 2022;27(9):2941. doi: 10.3390/molecules27092941, PMID 35566292.

Kuperkar K, Patel D, Atanase LI, Bahadur P. Amphiphilic block copolymers: their structures, and self-assembly to polymeric micelles and polymersomes as drug delivery vehicles. Polymers. 2022;14(21):4702. doi: 10.3390/polym14214702, PMID 36365696.

Agwa MM, Sabra S. Lactoferrin coated or conjugated nanomaterials as an active targeting approach in nanomedicine. Int J Biol Macromol. 2021;167:1527-43. doi: 10.1016/j.ijbiomac.2020.11.107, PMID 33212102.

Liyanage PY, Hettiarachchi SD, Zhou Y, Ouhtit A, Seven ES, Oztan CY. Nanoparticle-mediated targeted drug delivery for breast cancer treatment. Biochim Biophys Acta Rev Cancer. 2019;1871(2):419-33. doi: 10.1016/j.bbcan.2019.04.006, PMID 31034927.

Massodi I, Thomas E, Raucher D. Application of thermally responsive elastin-like polypeptide fused to a lactoferrin-derived peptide for treatment of pancreatic cancer. Molecules. 2009;14(6):1999-2015. doi: 10.3390/molecules14061999, PMID 19513001.

Hafez DA, Elkhodairy KA, Teleb M, Elzoghby AO. Nanomedicine-based approaches for improved delivery of phyto-therapeutics for cancer therapy. Expert Opin Drug Deliv. 2020;17(3):279-85. doi: 10.1080/17425247.2020.1723542, PMID 31997666.

Shanko ES, van de Burgt Y, Anderson PD, den Toonder JM. Microfluidic magnetic mixing at low reynolds numbers and in stagnant fluids. Micromachines. 2019;10(11):731. doi: 10.3390/mi10110731, PMID 31671753.

Jaradat E, Weaver E, Meziane A, Lamprou DA. Microfluidics technology for the design and formulation of nanomedicines. Nanomaterials (Basel). 2021;11(12):3440. doi: 10.3390/nano11123440, PMID 34947789.

Kumar S, Anselmo AC, Banerjee A, Zakrewsky M, Mitragotri S. Shape and size-dependent immune response to antigen-carrying nanoparticles. J Control Release. 2015;220(A):141-8. doi: 10.1016/j.jconrel.2015.09.069, PMID 26437263.

Tintore M, Mazzini S, Polito L, Marelli M, Latorre A, Somoza A. Gold-coated superparamagnetic nanoparticles for single methyl discrimination in DNA aptamers. Int J Mol Sci. 2015;16(11):27625-39. doi: 10.3390/ijms161126046, PMID 26593913.

Stein R, Friedrich B, Mühlberger M, Cebulla N, Schreiber E, Tietze R. Synthesis and characterization of citrate-stabilized gold-coated superparamagnetic iron oxide nanoparticles for biomedical applications. Molecules. 2020;25(19):4425. doi: 10.3390/molecules25194425, PMID 32993144.

Logigan CL, Delaite C, Tiron CE, Peptu C, Popa M, Peptu CA. Chitosan grafted poly (Ethylene Glycol) methyl ether acrylate particulate hydrogels for drug delivery applications. Gels. 2022;8(8):494. doi: 10.3390/gels8080494, PMID 36005095.

Mosafer J, Teymouri M. Comparative study of superparamagnetic iron oxide/doxorubicin co-loaded poly (lactic-co-glycolic acid) nanospheres prepared by different emulsion solvent evaporation methods. Artif Cells Nanomed Biotechnol. 2018;46(6):1146-55. doi: 10.1080/21691401.2017.1362415, PMID 28789586.

Gola A, Kozłowska M, Musiał W. Influence of the poly(ethylene glycol) methyl ether methacrylates on the selected physicochemical properties of thermally sensitive polymeric particles for controlled drug delivery. Polymers. 2022;14(21):4729. doi: 10.3390/polym14214729, PMID 36365721.

Braim S, Spiewak K, Brindell M, Heeg D, Alexander C, Monaghan T. Lactoferrin-loaded alginate microparticles to target clostridioides difficile infection. J Pharm Sci. 2019;108(7):2438-46. doi: 10.1016/j.xphs.2019.02.025, PMID 30851342.

Mitra A, Dey B. Chitosan microspheres in novel drug delivery systems. Indian J Pharm Sci. 2011;73(4):355-66. doi: 10.4103/0250-474X.95607, PMID 22707817.

SMART CHITOSAN-BASED MICROBEAD FORMULATION FOR COLON-TARGETED DELIVERY OF LACTOFERRIN

Authors

DOI:

Keywords:

Abstract

Downloads

References

Published

How to Cite

Issue

Section