EUDRAGIT COATED ALGINATE BEADS BEARING OXALIPLATIN LOADED LIPOSOMES: FORMULATION, OPTIMIZATION AND IN VITRO CHARACTERIZATION

Authors

  • ANKITA TIWARI Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar (M. P.), India 470003
  • SANJAY K. JAIN Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar (M. P.), India 470003

DOI:

https://doi.org/10.22159/ijap.2021v13i6.43199

Keywords:

Oxaliplatin loaded liposomes, Formulation, Optimization, In vitro characterization

Abstract

Objective: The present investigation aimed to develop and characterize Eudragit S-100 coated alginate beads bearing oxaliplatin loaded liposomes for colon-specific drug delivery.

Methods: Liposomes were formulated by the thin-film hydration method. The process and formulation variables were optimized by Box-Behnken design (BBD) with the help of Design-Expert® Software. Three independent variables taken were HSPC: Chol molar ratio (X1), hydration time (X2), and sonication time (X3). The response variables selected were entrapment efficiency of oxaliplatin, polydispersity index, and vesicle size.

Results: The liposomes possessed an average vesicle size of 110.1±2.8 nm, PDI 0.096±0.3, zeta potential of-6.70±1.4 mV, and entrapment efficiency of 27.65%. The beads were characterized for their size, in vitro drug release, and swelling index. The degree of swelling of the beads was found to be 2.3 fold higher at pH 7.4 than at pH 1.2. The in vitro drug release depicted a sustained drug release in 48 h.

Conclusion: The outcomes of the study proposed that the developed system can be effectively used for site-specific drug delivery to the colon via the oral route.

Downloads

Download data is not yet available.

References

Siegel R, DeSantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin. 2014;64(2):104-17. doi: 10.3322/caac.21220, PMID 24639052.

Gupta S, Provenzale D, Regenbogen SE, Hampel H, Slavin TP, Hall MJ, Llor X, Chung DC, Ahnen DJ, Bray T, Cooper G, Early DS, Ford JM, Giardiello FM, Grady W, Halverson AL, Hamilton SR, Klapman JB, Larson DW, Lazenby AJ, Lynch PM, Markowitz AJ, Mayer RJ, Ness RM, Samadder NJ, Shike M, Sugandha S, Weiss JM, Dwyer MA, Ogba N. NCCN guidelines insights: Genetic/Familial high-risk assessment: Colorectal, version 3.2017. J Natl Compr Canc. 2017;15(12):1465-75. doi: 10.6004/jnccn.2017.0176, PMID 29223984.

Fong CW. Platinum anti-cancer drugs: free radical mechanism of Pt-DNA adduct formation and anti-neoplastic effect. Free Radic Biol Med. 2016;95:216-29. doi: 10.1016/j.freeradbiomed.2016.03.006, PMID 27012421.

BH JG, Shankar S, Munisamy M, RS A, Sagar V. Development of pH-dependent chronomodulated delivery systems of 5-fluorouracil and oxaliplatin to treat colon cancer. Int J Appl Pharm. 2020;12(5):118-30.

Perego P, Robert J. Oxaliplatin in the era of personalized medicine: from mechanistic studies to clinical efficacy. Cancer Chemother Pharmacol. 2016;77(1):5-18. doi: 10.1007/s00280-015-2901-x, PMID 26589793.

Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4(2):145-60. doi: 10.1038/nrd1632, PMID 15688077.

Atara SA, Soniwala MM. Formulation and evaluation of pectin-calcium chloride beads of azathioprine for colon targeted drug delivery system. Int J Pharm Pharm Sci. 2018;10(1):172-9. doi: 10.22159/ijpps.2018v10i1.23175.

Ramanathan M, Subramanian L. Formulation and evaluation of colon targeted matrix tablets of ibuprofen. Asian J. Pharm. Res Dev. 2018;6(2):9-19.

Madhavi C, Babu PK, Maruthi Y, Parandhama A, Reddy OS, Rao KC, Subha Mcs, Kumar RJ. Sodium alginate–locust bean gum IPN hydrogel beads for the controlled delivery of nimesulide-anti-inflammatory drug. Int J Pharm Pharm Sci. 2017;9(10):245-52. doi: 10.22159/ijpps.2017v9i10.20231.

Ferreira SL, Bruns RE, Ferreira HS, Matos GD, David JM, Brandao GC, da Silva EG, Portugal LA, dos Reis PS, Souza AS, dos Santos WN. Box-Behnken design: an alternative for the optimization of analytical methods. Anal Chim Acta. 2007;597(2):179-86. doi: 10.1016/j.aca.2007.07.011, PMID 17683728.

Bangham AD. Membrane models with phospholipids. Prog Biophys Mol Biol. 1968;18:29-95. doi: 10.1016/0079-6107(68)90019-9, PMID 4894874.

Mezei M, Gulasekharam V. Liposomes- a selective drug delivery system for the topical route of administration: gel dosage form. J Pharm Pharmacol. 1982;34(7):473-4. doi: 10.1111/j.2042-7158.1982.tb04767.x, PMID 6126554.

Alagumurthi N, Palaniradja K, Soundararajan V. Optimization of grinding process through design of experiment (DOE)- A comparative study. Mater Manuf Processes. 2006;21(1):19-21. doi: 10.1080/AMP-200060605.

Giovanni M. Response surface methodology and product optimization. Food Technol. 1983.

Saraf S, Jain A, Tiwari A, Verma A, Jain SK. Engineered liposomes bearing camptothecin analogue for tumour targeting: in vitro and ex-vivo studies. J Liposome Res. 2020 Aug 11:1-16. doi: 10.1080/08982104.2020.1801725, PMID 32718195.

Galpin IJ, Kenner GW, Ohlsen SR, Ramage R. Gel filtration of protected peptides on Sephadex G-50 in hexamethylphosphoramide containing 5% water. J Chromatogr. 1975;106(1):125-9. doi: 10.1016/s0021-9673(01)81054-2, PMID 1150783.

Jain A, Jain SK, Ganesh N, Barve J, Beg AM. Design and development of ligand-appended polysaccharidic nanoparticles for the delivery of oxaliplatin in colorectal cancer. Nanomedicine. 2010;6(1):179-90. doi: 10.1016/j.nano.2009.03.002, PMID 19447205.

Xing L, Dawei C, Liping X, Rongqing Z. Oral colon-specific drug delivery for bee venom peptide: development of a coated calcium alginate gel beads-entrapped liposome. J Control Release. 2003;93(3):293-300. doi: 10.1016/j.jconrel. 2003.08.019, PMID 14644579.

Huyghebaert N, Vermeire A, Remon JP. In vitro evaluation of coating polymers for enteric coating and human ileal targeting. Int J Pharm. 2005;298(1):26-37. doi: 10.1016/ j.ijpharm.2005.03.032, PMID 15894443.

Xie Cl, Lee SS, Choung S, Kang SS, Choi YJ. Preparation and optimisation of liposome‐in‐alginate beads containing oyster hydrolysate for sustained release. Int J Food Sci Technol. 2016;51(10):2209-16. doi: 10.1111/ijfs.13207.

Lee BJ, Min GH. Preparation and release characteristics of polymer-reinforced and coated alginate beads. Arch Pharm Res. 1995;18(3):183-8. doi: 10.1007/BF02979193.

Souder J, Ellenbogen W. Control of d-amphetamine sulphate sustained release capsule. Drug Stand. 1985;26:77-9.

Segale L, Giovannelli L, Mannina P, Pattarino F. Calcium alginate and calcium alginate-chitosan beads containing celecoxib solubilized in a self-emulsifying phase. Scientifica. 2016;2016:5062706. doi: 10.1155/2016/5062706, PMID 27127680.

Wang T, Jiang Y, Chu H, Liu X, Dai Y, Wang D. Doxorubicin and lovastatin co-delivery liposomes for synergistic therapy of liver cancer. J Drug Deliv Sci Technol. 2019;52:452-9. doi: 10.1016/j.jddst.2019.04.045.

Yang S, Chen J, Zhao D, Han D, Chen X. Comparative study on preparative methods of DC-Chol/DOPE liposomes and formulation optimization by determining encapsulation efficiency. Int J Pharm. 2012;434(1-2):155-60. doi: 10.1016/j.ijpharm.2012.05.041, PMID 22643228.

Narayan R, Singh M, Ranjan O, Nayak Y, Garg S, Shavi GV, Nayak UY. Development of risperidone liposomes for brain targeting through intranasal route. Life Sci. 2016;163:38-45. doi: 10.1016/j.lfs.2016.08.033, PMID 27593571.

Kumari A, Jain A, Hurkat P, Tiwari A, Jain SK. Eudragit S100 coated microsponges for colon targeting of prednisolone. Drug Dev Ind Pharm. 2018;44(6):902-13. doi: 10.1080/03639045.2017.1420079, PMID 29260916.

Chaurasia M, Chourasia MK, Jain NK, Jain A, Soni V, Gupta Y, Jain SK. Cross-linked guar gum microspheres: A viable approach for improved delivery of anticancer drugs for the treatment of colorectal cancer. AAPS PharmSciTech. 2006;7(3):74. doi: 10.1208/pt070374, PMID 17025254.

Seeli DS, Dhivya S, Selvamurugan N, Prabaharan M. Guar gum succinate-sodium alginate beads as a pH-sensitive carrier for colon-specific drug delivery. Int J Biol Macromol. 2016;91:45-50. doi: 10.1016/j.ijbiomac.2016.05.057, PMID 27212216.

Published

07-11-2021

How to Cite

TIWARI, A., & JAIN, S. K. (2021). EUDRAGIT COATED ALGINATE BEADS BEARING OXALIPLATIN LOADED LIPOSOMES: FORMULATION, OPTIMIZATION AND IN VITRO CHARACTERIZATION. International Journal of Applied Pharmaceutics, 13(6), 170–177. https://doi.org/10.22159/ijap.2021v13i6.43199

Issue

Section

Original Article(s)