A REVIEW: ANTI-CANCER NATURAL PRODUCT DRUG DELIVERY SYSTEM DOSAGE FORM AND EVALUATION

RIZKA KHOIRUNNISA GUNTINA; IYAN SOPYAN; ADE ZUHROTUN

doi:10.22159/ijap.2021.v13s4.43815

Authors

RIZKA KHOIRUNNISA GUNTINA Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjajaran, Jatinangor, Indonesia 45363
IYAN SOPYAN Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjajaran, Jatinangor, Indonesia 45363, Center of Drug Development, Faculty of Pharmacy, Universitas Padjajaran, Jatinangor, Indonesia 45363
ADE ZUHROTUN Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjajaran, Jatinangor, Indonesia 45363

DOI:

https://doi.org/10.22159/ijap.2021.v13s4.43815

Keywords:

Drug delivery system, Extract, Evaluation, Matrix

Abstract

A drug delivery system is a system in which a drug is released from a pharmaceutical dosage form to achieve the desired pharmacological effect. The system consists of conventional and new drug delivery systems. In the new drug delivery system, polymers are used as a matrix. The aim of this article is to find out and understand the formulation and evaluation of natural ingredients that have anticancer activity with different dosage forms and the basis for developing these dosages. Journal searches in this review came from primary data sources on the internet. Journal searches were carried out using a search engine such as Google Scholar, PubMed, and ScienceDirect. In recent years, natural products, such as extract, fraction, and isolate, are getting attention to help treat cancer. Because of their low solubility and bioavailability, the effectiveness tends to be lower than synthetic drugs. Therefore, a dosage form with a new drug delivery system was made to overcome the problem. The dosage forms commonly made are patch, suspension, powder, and emulsion with a new drug delivery system. To ensure the product that has been made met the requirements, they need to be evaluated with various methods like In vitro Study, morphology study, particle size study, and others. Cancer treatment using the natural product can be delivered through several dosage forms like patch, suspension, powder, and emulsion, with specific formulation and manufacturing methods based on several considerations such as natural ingredients properties, dosage form selection, excipient properties, and the purpose of the formulation. Dosage forms that has been made are then evaluated using several evaluation methods.

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References

Tiwari G, Tiwari R, Sriwastawa B, Bhati L, Pandey S, Pandey P, Bannerjee SK. Drug delivery systems: an updated review. Int J Pharm Investig. 2012;2(1):2-11. doi: 10.4103/2230-973X.96920, PMID 23071954.

Rojo J, Sousa Herves A, Mascaraque A. 1.24-perspectives of carbohydrates in drug discovery. In: Oxford: Elsevier; 2017. p. 577-610. Available from: https://www.sciencedirect.com [Last 19 Apr 2021].

Atanasov AG, Waltenberger B, Pferschy Wenzig EM, Linder T, Wawrosch C, Uhrin P, et al. Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv. 2015;33(8):1582-614. doi: 10.1016/j.biotechadv.2015.08.001, PMID 26281720.

Atanasov AG, Zotchev SB, Dirsch VM, International Natural Product Sciences Taskforce, Supuran CT. Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov. 2021;20(3):200-16. doi: 10.1038/s41573-020-00114-z, PMID 33510482.

Sahoo CK, Reddy GS, Vojjala A, Reddy BV. Bioavailability enhancement for poorly soluble drugs: a review. IIJS. 2018. p. 1-6.

Abuzar SM, Hyun SM, Kim JH, Park HJ, Kim MS, Park JS, Hwang SJ. Enhancing the solubility and bioavailability of poorly water-soluble drugs using supercritical antisolvent (SAS) process. Int J Pharm. 2018;538(1-2):1-13. doi: 10.1016/j.ijpharm. 2017.12.041, PMID 29278733.

Rizvi SAA, Saleh AM. Applications of nanoparticle systems in drug delivery technology. Saudi Pharm J. 2018;26(1):64-70. doi: 10.1016/j.jsps.2017.10.012, PMID 29379334.

Dhanalakshmi S, Harikrishnan N, Devi M, Keerthana V, Vijayalakshmi. Fabrication and evaluation of herbal transdermal flim from hibiscus rosa sinensis. Int J Curr Pharm Sci. 2019;11(5):101-5. doi: 10.22159/ijcpr.2019v11i5.35716.

Karpagavalli L, Mahaeswaran A, Praveena P, Sharmila S, Meena B. Formulation and evaluation of transdermal patches of curcumin. Int J Novel Trends Pharm Sci. 2017;7(1):22-6.

Saleem MN, Idris M. Formulation design and development of a Unani transdermal patch for antiemetic therapy and its pharmaceutical evaluation. Scientifica. 2016;2016:7602347. doi: 10.1155/2016/7602347, PMID 27403377.

Savula J, Krishna MKS, Anwesh H, Prashanth K. Formulation and evaluation of herbal transdermal patches. World J Pharm Res. 2017;6(13):365-74.

Ansel HC, Allen LV, Popovich NG. Pharmauceutical dosage forms and drug delivery system. Philadelphia: Lippincott Williams and Wilkins; 1999.

Ubaidulla U, Reddy MVS, Ruckmani K, Ahmad FJ, Khar RK. Transdermal therapeutic system of carvedilol: effect of hydrophilic and hydrophobic matrix on in vitro and in vivo characteristics. AAPS PharmSciTech. 2007;8(1):2. doi: 10.1208/pt0801002, PMID 17408218.

Patel M, Patel B, Patel R, Jayvadan P, Bharadia P, Patel M. Carbopol: A versatile polymer. Drug Deliv Technol. 2006;3(6):32-43.

Shabbir M, Ali S, Raza M, Sharif A, Akhtar FM, Manan A, Fazli AR, Younas N, Manzoor I. Effect of hydrophilic and hydrophobic polymer on in vitro dissolution and permeation of bisoprolol fumarate through transdermal patch. Acta Pol Pharm. 2017;74(1):187-97. PMID 29474775.

Ilhan Ayisigi E, Ulucan F, Saygili E, Saglam Metiner P, Gulce-Iz S, Yesil Celiktas O. Nano-vesicular formulation of propolis and cytotoxic effects in a 3D spheroid model of lung cancer. J Sci Food Agric. 2020;100(8):3525-35. doi: 10.1002/jsfa.10400, PMID 32239766.

Baranei M, Taheri RA, Tirgar M, Saeidi A, Oroojalian F, Uzun L, Asefnejad A, Wurm FR, Goodarzi V. Anticancer effect of green tea extract (GTE)-Loaded pH-responsive niosome coated with PEG against different cell lines. Mater Today Commun. 2021;26. doi: 10.1016/j.mtcomm.2020.101751, PMID 101751.

Chen R, Wang S, Zhang J, Chen M, Wang Y. Aloe-emodin loaded solid lipid nanoparticles: formulation design and in vitro anti-cancer study. Drug Deliv. 2015;22(5):666-74. doi: 10.3109/10717544.2014.882446, PMID 24512431.

Donoso Quezada J, Guajardo Flores D, Gonzalez Valdez J. Exosomes as nanocarriers for the delivery of bioactive compounds from black bean extract with antiproliferative activity in cancer cell lines. Mater Today Proc. 2019;13:362-9. doi: 10.1016/j.matpr.2019.03.166.

Shi F, Zhao JH, Liu Y, Wang Z, Zhang YT, Feng NP. Preparation and characterization of solid lipid nanoparticles loaded with frankincense and myrrh oil. Int J Nanomed. 2012;7:2033-43. doi: 10.2147/IJN.S30085, PMID 22619540.

Lee SY, Lee JJ, Nam S, Kang WS, Yoon IS, Cho HJ. Fabrication of polymer matrix-free nanocomposites based on Angelica gigas Nakai extract and their application to breast cancer therapy. Colloids Surf B Biointerfaces. 2017;159:781-90. doi: 10.1016/j.colsurfb.2017.08.040, PMID 28886514.

Wang Y, Yu H, Wang S, Gai C, Cui X, Xu Z, Li W, Zhang W. Targeted delivery of quercetin by nanoparticles based on chitosan sensitizing paclitaxel-resistant lung cancer cells to paclitaxel. Mater Sci Eng C Mater Biol Appl. 2021;119:111442. doi: 10.1016/j.msec.2020.111442.

Sabry S, El Hakim Ramadan A, Abd Elghany M, Okda T, Hasan A. Formulation, characterization, and evaluation of the anti-tumor activity of nanosized galangin loaded niosomes on chemically induced hepatocellular carcinoma in rats. J Drug Deliv Sci Technol. 2021;61. doi: 10.1016/j.jddst.2020.102163, PMID 102163.

Saleh T, Soudi T, Shojaosadati SA. Aptamer functionalized curcumin-loaded human serum albumin (HSA) nanoparticles for targeted delivery to HER-2 positive breast cancer cells. Int J Biol Macromol. 2019;130:109-16. doi: 10.1016/j.ijbiomac.2019.02.129, PMID 30802519.

Liu Q, Wu F, Chen Y, Alrashood ST, Alharbi SA. Anti-human colon cancer properties of a novel chemotherapeutic supplement formulated by gold nanoparticles containing Allium sativum L. leaf aqueous extract and investigation of its cytotoxicity and antioxidant activities. Arab J Chem. 2021;14(4). doi: 10.1016/j.arabjc.2021.103039, PMID 103039.

Mughees M, Wajid S, Samim M. Cytotoxic potential of artemisia absinthium extract loaded polymeric nanoparticles against breast cancer cells: insight into the protein targets. Int J Pharm. 2020;586:119583. doi: 10.1016/j.ijpharm.2020.119583.

Barhoum A, Garcia Betancourt ML, Rahier H, Van Assche G. Physicochemical characterization of nanomaterials: polymorph, composition, wettability, and thermal stability. In: Barhoum A, Makhlouf ASH, editors. Elsevier; 2018. p. 255-78. Available from: https://www.sciencedirect.com. [Last accessed on 06 Aug 2021].

Meena J, Gupta A, Ahuja R, Singh M, Bhaskar S, Panda AK. Inorganic nanoparticles for natural product delivery: a review. Environ Chem Lett. 2020;18(6):2107-18. doi: 10.1007/s10311-020-01061-2.

Kianamiri S, Dinari A, Sadeghizadeh M, Rezaei M, Daraei B, Bahsoun NE-H, Nomani A. Mitochondria-targeted polyamidoamine dendrimer–curcumin construct for hepatocellular cancer treatment. Mol Pharm. 2020;17(12):4483-98. doi: 10.1021/acs.molpharmaceut.0c00566, PMID 33205974.

Ge P, Niu B, Wu Y, Xu W, Li M, Sun H, Zhou H, Zhang X, Xie J. Enhanced cancer therapy of celastrol in vitro and in vivo by smart dendrimers delivery with specificity and biosafety. Chem Eng J. 2020;383. doi: 10.1016/j.cej.2019.123228, PMID 123228.

Haggag YA, Ibrahim RR, Hafiz AA. Design, formulation and in vivo evaluation of novel honokiol-loaded pegylated PLGA nanocapsules for treatment of breast cancer. IJN. 2020;15:1625-42. doi: 10.2147/IJN.S241428.

Gera M, Kim N, Ghosh M, Sharma N, Huynh DL, Chandimali N, Koh H, Zhang JJ, Kang TY, Park YH, Kwon T, Jeong DK. Synthesis and evaluation of the antiproliferative efficacy of BRM270 phytocomposite nanoparticles against human hepatoma cancer cell lines. Mater Sci Eng C Mater Biol Appl. 2019;97:166-76. doi: 10.1016/j.msec.2018.11.055, PMID 30678901.

Chen J, Li Y, Fang G, Cao Z, Shang Y, Alfarraj S, Ali Alharbi S, Li J, Yang S, Duan X. Green synthesis, characterization, cytotoxicity, antioxidant, and anti-human ovarian cancer activities of Curcumae kwangsiensis leaf aqueous extract green-synthesized gold nanoparticles. Arab J Chem. 2021;14(3). doi: 10.1016/j.arabjc.2021.103000, PMID 103000.

Li Y, Li X, Lu Y, Chaurasiya B, Mi G, Shi D, Chen D, Webster TJ, Tu J, Shen Y. Co-delivery of Poria cocos extract and doxorubicin as an ’all-in-one’ nanocarrier to combat breast cancer multidrug resistance during chemotherapy. Nanomed Nanotechnol Biol Med. 2020;23. doi: 10.1016/j.nano.2019.102095, PMID 102095.

Pillai SC, Borah A, Jindal A, Jacob EM, Yamamoto Y, Kumar DS. BioPerine encapsulated nanoformulation for overcoming drug-resistant breast cancers. Asian J Pharm Sci. 2020;15(6):701-12. doi: 10.1016/j.ajps.2020.04.001, PMID 33363626.

Shah HS, Usman F, Ashfaq Khan M, Khalil R, Ul-Haq Z, Mushtaq A, Qaiser R, Iqbal J. Preparation and characterization of anticancer niosomal withaferin–a formulation for improved delivery to cancer cells: in vitro, in vivo, and in silico evaluation. J Drug Deliv Sci Technol. 2020;59. doi: 10.1016/j.jddst.2020.101863, PMID 101863.

Pathak M, Pathak P, Rimac H, Grishina M, Bagale U, Kumar V, Rahul Majee, Vladimir Potemkin, Verma A. Attenuation of hepatic and breast cancer cells by Polygonatum verticillatum embedded silver nanoparticles. Biocatal Agric Biotechnol. 2020;30. doi: 10.1016/j.bcab.2020.101863, PMID 101863.

Zafar S, Akhter S, Ahmad I, Hafeez Z, Alam Rizvi MM, Jain GK, Ahmad FJ. Improved chemotherapeutic efficacy against resistant human breast cancer cells with co-delivery of docetaxel and thymoquinone by chitosan grafted lipid nanocapsules: formulation optimization, in vitro and in vivo studies. Colloids Surf B Biointerfaces. 2020;186:110603. doi: 10.1016/j.colsurfb.2019.110603.

Li S, Al-Misned FA, El-Serehy HA, Yang L. Green synthesis of gold nanoparticles using aqueous extract of Mentha longifolia leaf and investigation of its anti-human breast carcinoma properties in the in vitro condition. Arab J Chem. 2021;14(2). doi: 10.1016/j.arabjc.2020.102931, PMID 102931.

Dinparvar S, Bagirova M, Allahverdiyev AM, Abamor ES, Safarov T, Aydogdu M, Aktas D. A nanotechnology-based new approach in the treatment of breast cancer: biosynthesized silver nanoparticles using cuminum cyminum L. seed extract. J Photochem Photobiol B. 2020;208:111902. doi: 10.1016/j.jphotobiol.2020.111902.

Periasamy VS, Athinarayanan J, Alshatwi AA. Anticancer activity of an ultrasonic nanoemulsion formulation of Nigella sativa L. essential oil on human breast cancer cells. Ultrason Sonochem. 2016;31(31):449-55. doi: 10.1016/j.ultsonch.2016.01.035, PMID 26964971.

Sabapati M, Palei NN, CK AK, Molakpogu RB. Solid lipid nanoparticles of Annona muricata fruit extract: formulation, optimization and in vitro cytotoxicity studies. Drug Dev Ind Pharm. 2019;45(4):577-86. doi: 10.1080/03639045.2019.1569027, PMID 30663427.

Wang S, Chen T, Chen R, Hu Y, Chen M, Wang Y. Emodin loaded solid lipid nanoparticles: preparation, characterization and antitumor activity studies. Int J Pharm. 2012;430(1-2):238-46. doi: 10.1016/j.ijpharm.2012.03.027, PMID 22465546.

Zamani H, Rastegari B, Varamini M. Antioxidant and anti-cancer activity of Dunaliella salina extract and oral drug delivery potential via nano-based formulations of gum arabic coated magnetite nanoparticles. J Drug Deliv Sci Technol. 2019 Dec 1;54. doi: 10.1016/j.jddst.2019.101278, PMID 101278.

Luesakul U, Puthong S, Sansanaphongpricha K, Muangsin N. Quaternized chitosan-coated nanoemulsions: A novel platform for improving the stability, anti-inflammatory, anti-cancer and transdermal properties of plai extract. Carbohydr Polym. 2020;230:115625. doi: 10.1016/j.carbpol.2019.115625.

Vasconcelos AG, Valim MO, Amorim AGN, do Amaral CP, de Almeida MP, Borges TKS, Socodato R, Portugal CC, Brand GD, Mattos JSC, Relvas J, Placido A, Eaton P, Ramos DAR, Kuckelhaus SAS, Leite JRSA. Cytotoxic activity of poly-ɛ-caprolactone lipid-core nanocapsules loaded with lycopene-rich extract from red guava (Psidium guajava L.) on breast cancer cells. Food Res Int. 2020;136. doi: 10.1016/j.foodres.2020.109548, PMID 109548.

Loo YS, Madheswaran T, Rajendran R, Bose RJC. Encapsulation of berberine into liquid crystalline nanoparticles to enhance its solubility and anticancer activity in MCF7 human breast cancer cells. J Drug Deliv Sci Technol. 2020;57. doi: 10.1016/j.jddst.2020.101756, PMID 101756.

Fraguas Sanchez AI, Fernandez Carballido A, Simancas Herbada R, Martin Sabroso C, Torres Suarez AI. CBD loaded microparticles as a potential formulation to improve paclitaxel and doxorubicin-based chemotherapy in breast cancer. Int J Pharm. 2020;574:118916. doi: 10.1016/j.ijpharm.2019.118916.

Cerda Opazo P, Gotteland M, Oyarzun Ampuero FA, Garcia L. Design, development and evaluation of nanoemulsion containing avocado peel extract with anticancer potential: A novel biological active ingredient to enrich food. Food Hydrocoll. 2021;111. doi: 10.1016/j.foodhyd.2020.106370, PMID 106370.

Pant M, Dubey S, Patanjali PK, Naik SN, Sharma S. Insecticidal activity of eucalyptus oil nanoemulsion with Karanja and jatropha aqueous filtrates. Int Biodeterior Biodegrad. 2014;91:119-27. doi: 10.1016/j.ibiod.2013.11.019.

Godugu C, Doddapaneni R, Singh M. Honokiol nanomicellar formulation produced increased oral bioavailability and anticancer effects in triple negative breast cancer (TNBC). Colloids Surf B Biointerfaces. 2017;153:208-19. doi: 10.1016/j.colsurfb.2017.01.038, PMID 28249200.

Wang J, Yang H, Li Q, Wu X, Di G, Fan J, Wei D, Guo C. Novel nanomicelles based on rebaudioside A: A potential nanoplatform for oral delivery of honokiol with enhanced oral bioavailability and antitumor activity. Int J Pharm. 2020;590:119899. doi: 10.1016/j.ijpharm.2020.119899.

Nam S, Lee JJ, Lee SY, Jeong JY, Kang WS, Cho HJ. Angelica gigas Nakai extract-loaded fast-dissolving nanofiber based on poly(vinyl alcohol) and soluplus for oral cancer therapy. Int J Pharm. 2017;526(1-2):225-34. doi: 10.1016/j.ijpharm.2017.05.004, PMID 28478278.

Nayak D, Minz AP, Ashe S, Rauta PR, Kumari M, Chopra P, Nayak B. Synergistic combination of antioxidants, silver nanoparticles and chitosan in a nanoparticle based formulation: characterization and cytotoxic effect on MCF-7 breast cancer cell lines. J Colloid Interface Sci. 2016;470:142-52. doi: 10.1016/j.jcis.2016.02.043, PMID 26939078.

Zhang F, Li R, Yan M, Li Q, Li Y, Wu X. Ultra-small nanocomplexes based on polyvinylpyrrolidone K-17PF: A potential nanoplatform for the ocular delivery of kaempferol. Eur J Pharm Sci. 2020;147:105289. doi: 10.1016/j.ejps.2020.105289.

Mohammad IS, Teng C, Chaurasiya B, Yin L, Wu C, He W. Drug-delivering-drug approach-based codelivery of paclitaxel and disulfiram for treating multidrug-resistant cancer. Int J Pharm. 2019;557:304-13. doi: 10.1016/j.ijpharm.2018.12.067, PMID 30599232.

Ravikumar R, Ganesh M, Senthil V, Ramesh YV, Jakki SL, Choi EY. Tetrahydro curcumin loaded PCL-PEG electrospun transdermal nanofiber patch: preparation, characterization, and in vitro diffusion evaluations. J Drug Deliv Sci Technol. 2018;44:342-8. doi: 10.1016/j.jddst.2018.01.016.

Golinejad S, Mirjalili MH. Fast and cost-effective preparation of plant cells for scanning electron microscopy (SEM) analysis. Anal Biochem. 2020;609:113920. doi: 10.1016/j.ab.2020.113920.

El Sayeh F Abou El Ela A, Abbas Ibrahim M, Alqahtani Y, Almomen A, Sfouq Aleanizy F. Fluconazole nanoparticles prepared by antisolvent precipitation technique: physicochemical, in vitro, ex vivo and in vivo ocular evaluation. Saudi Pharm J. 2021;29(6):576-85. doi: 10.1016/j.jsps.2021.04.018, PMID 34194264.

Sinha P, Srivastava N, Rai VK, Mishra R, Ajayakumar PV, Yadav NP. A novel approach for dermal controlled release of salicylic acid for improved anti-inflammatory action: combination of hydrophilic-lipophilic balance and response surface methodology. J Drug Deliv Sci Technol. 2019;52:870-84. doi: 10.1016/j.jddst.2019.06.007.

Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, Khorasani S, Mozafari MR. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018;10(2):57. doi: 10.3390/pharmaceutics10020057, PMID 29783687.

Gonzalez Reza RM, Quintanar Guerrero D, Del Real Lopez A, Pinon Segundo E, Zambrano Zaragoza ML. Effect of sucrose concentration and pH onto the physical stability of β-carotene nanocapsules. LWT. 2018;90:354-61. doi: 10.1016/j.lwt.2017.12.044.

Sizochenko N, Mikolajczyk A, Syzochenko M, Puzyn T, Leszczynski J. Zeta potentials (ζ) of metal oxide nanoparticles: A meta-analysis of experimental data and a predictive neural networks modeling. NanoImpact. 2021;22. doi: 10.1016/j.impact.2021.100317:, 100317PMID 100317.

Lv Y, He H, Qi J, Lu Y, Zhao W, Dong X, Wu W. Visual validation of the measurement of entrapment efficiency of drug nanocarriers. Int J Pharm. 2018;547(1-2):395-403. doi: 10.1016/j.ijpharm.2018.06.025, PMID 29894757.

Wen J, Arthur K, Chemmalil L, Muzammil S, Gabrielson J, Jiang Y. Applications of differential scanning calorimetry for thermal stability analysis of proteins: qualification of DSC. J Pharm Sci. 2012;101(3):955-64. doi: 10.1002/jps.22820, PMID 22147423.

Pleguezuelos Villa M, Merino Sanjuan M, Hernandez MJ, Nacher A, Peris D, Hidalgo I, Soler L, Sallan M, Merino V. Relationship between rheological properties, in vitro release and in vivo equivalency of topical formulations of diclofenac. Int J Pharm. 2019;572:118755. doi: 10.1016/j.ijpharm.2019.118755.