Author(s): Tiara Mega Kusuma, Teuku Nanda Saifullah Sulaiman, Ronny Martien


DOI: 10.52711/0974-360X.2021.00349   

Address: Tiara Mega Kusuma1*, Teuku Nanda Saifullah Sulaiman2, Ronny Martien2
1Department of Pharmaceutics, Faculty of Health Science, Universitas Muhammadiyah Magelang, Indonesia.
2Department of Pharmaceutics, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia.
*Corresponding Author

Published In:   Volume - 14,      Issue - 4,     Year - 2021

Insulin is a macromolecular polypeptide hormone with low drug stability and permeability along the digestive tract. The nanoparticle delivery system has been proven to be able to increase the bioavailability of per-oral insulin. However, the formulation of insulin nanoparticles using chitosan and pectin polymers has not been widely studied. The purpose of this research is to figure out the physical characteristics and profile of insulin release from nanoparticle formulas made with ionic gelation techniques using chitosan and pectin polymers. The 0.1% insulin nanoparticle formula is made with variations of 2 levels of medium molecular chitosan and pectin concentrations to obtain 4 formulas, i.e. F1 (0.01%; 0.1%), F2 (0.03%; 0.1%), F3 (0.01%; 0.2%), and F4 (0.03%; 0.2%). The optimum formula is determined by the factorial design method contained in the Design Expert program using response characteristics in the form of percentage of the entrapment efficiency and zeta potential value. The selected formula is then tested for particle size and shape, and insulin release profile in vitro. The particle size and morphology are observed with TEM (Transmission Electron Microscope), while the insulin release profile is determined on HCl buffer media pH 1.2 and PBS pH 6.8. The optimization results of the formula show that F1 is the optimum formula with a desirability value of 0.786. The selected formula shows that the entrapment efficiency is 57.66%, the zeta potential is 12.0 mV, the shape of particles is spherical, and the size is <500 nm. In vitro studies show the profile of insulin release from the matrix following the Weibull kinetics model on HCl and Korsmeyer-Peppas media on PBS media, using the Fickian diffusion method. Overall, the insulin nanoparticles obtained have met the expected characteristic of the nanoparticles.

Cite this article:
Tiara Mega Kusuma, Teuku Nanda Saifullah Sulaiman, Ronny Martien. Characteristics and Release Profile: Formula of Insulin Nanoparticles using Medium Molecular Weight Chitosan and Pectin Polymers. Research Journal of Pharmacy and Technology. 2021; 14(4):1973-8. doi: 10.52711/0974-360X.2021.00349

Tiara Mega Kusuma, Teuku Nanda Saifullah Sulaiman, Ronny Martien. Characteristics and Release Profile: Formula of Insulin Nanoparticles using Medium Molecular Weight Chitosan and Pectin Polymers. Research Journal of Pharmacy and Technology. 2021; 14(4):1973-8. doi: 10.52711/0974-360X.2021.00349   Available on:

1. Veber DF, Johnson SR, Cheng H, Smith BR, Ward KW, Kopple KD. Molecular Properties That Influence the Oral Bioavailability of Drug Candidates. J Med Chem. 2002;45: 2615-2623.
2. Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods. 2001;44(2000): 235-249.
3. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. 1997; 23: 3-25.
4. Moser EG, Morris AA, Garg SK. Emerging diabetes therapies and technologies. Diabetes Res Clin Pract. 2012;97(1):16-26. doi:10.1016/j.diabres.2012.01.027
5. Ohkubo Y, KIshikawa H, Araki E, et al. Intensive Insulin Therapy Prevents The Progression of Diabetic Microvascular Complications in Japanese Patients With Non-insulin-dependent Diabetes Mellitus: A Randomized Prospective 6-year Study. Diabetes Res Clin Pract. 1995;28: 103-117.
6. Su F, Lin K, Sonaje K, et al. Biomaterials Protease inhibition and absorption enhancement by functional nanoparticles for effective oral insulin delivery. Biomaterials. 2012;33(9):2801-2811. doi:10.1016/j.biomaterials.2011.12.038
7. Ku MS. Use of the Biopharmaceutical Classification System in Early Drug Development. AAPS J. 2008;10(1):208-212. doi:10.1208/s12248-008-9020-0
8. Lopes MA, Abrahim BA, Cabral LM, et al. Intestinal absorption of insulin nanoparticles: Contribution of M cells. Nanomedicine Nanotechnology, Biol Med. 2014. doi:10.1016/j.nano.2014.02.014
9. Sarmento B, Ribeiro A, Veiga F, Sampaio P, Neufeld R, Ferreira D. Alginate/Chitosan Nanoparticles are Effective for Oral Insulin Delivery. Pharm Res. 2007;24(12):2198-2206. doi:10.1007/s11095-007-9367-4
10. Avadi MR, Mir A, Sadeghi M, Dinarvand R, Rafiee-tehrani M. Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method. Nanomedicine Nanotechnology, Biol Med. 2010;6(1):58-63. doi:10.1016/j.nano.2009.04.007
11. Mukhopadhyay P, Sarkar K, Chakraborty M. Oral insulin delivery by self-assembled chitosan nanoparticles : In vitro and in vivo studies in diabetic animal model. Mater Sci Eng C. 2013;33(1):376-382. doi:10.1016/j.msec.2012.09.001
12. Debnath S, Kumar RS, Babu MN. Ionotropic gelation - A novel method to prepare chitosan nanoparticles Ionotropic Gelation – A Novel Method to Prepare Chitosan Nanoparticles. Res J Pharm Technol. 2017;4(4):492-495.
13. Divya L, Raju MB, Raut SY. Chitosan-Based Micro and Nanoparticles: A Promising System for Drug Delivery. Res J Pharm Technol. 2014;7(12):1463-1471.
14. Zhang H, Wu S, Tao Y, Zang L, Su Z. Preparation and Characterization of Water-Soluble Chitosan Nanoparticles as Protein Delivery System. J Nanomater. 2010;2010. doi:10.1155/2010/898910
15. Kiang T, Wen J, Lim HW, Leong KW. The effect of the degree of chitosan deacetylation on the efficiency of gene transfection. Biomaterials. 2004; 25:5293-5301. doi: 10.1016/j.biomaterials.2003.12.036
16. Turan K. Chitosan-DNA Nanoparticles: The Effect of Cell Type and Hydrolysis of Chitosan on In Vitro DNA Transfection. Pharm Dev Technol. 2006; 11:503-512. doi:10.1080/10837450600940873
17. Xu Y, Du Y. Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles. Int J Pharm. 2003; 250:215-226.
18. Bernabé P, Peniche C, Guaymas CU, Varadero C, Km N, Postal A. Swelling behavior of chitosan / pectin polyelectrolyte complex membranes. Effect of thermal cross-linking. Polym Bull. 2005; 55:367-375. doi:10.1007/s00289-005-0439-5
19. Oliveira GF, Ferrari PC, Carvalho LQ, Evangelista RC. Chitosan – pectin multiparticulate systems associated with enteric polymers for colonic drug delivery. Carbohydr Polym. 2010;82(3):1004-1009. doi: 10.1016/j.carbpol.2010.06.041
20. Pandey S, Mishra A, Raval P, Patel H, Gupta A, Shah D. Chitosan e pectin polyelectrolyte complex as a carrier for colon targeted drug delivery. J Young Pharm. 2013;5(4):160-166. doi: 10.1016/j.jyp.2013.11.002
21. Tsai R, Chen P, Kuo T, et al. Chitosan / pectin / gum Arabic polyelectrolyte complex : Process-dependent appearance , microstructure analysis and its application. Carbohydr Polym. 2014; 101:752-759. doi: 10.1016/j.carbpol.2013.10.008
22. Elsayed A, Al-remawi M, Qinna N, Farouk A, Al-sou KA, Badwan AA. Chitosan – Sodium Lauryl Sulfate Nanoparticles as a Carrier System for the In Vivo Delivery of Oral Insulin. AAPS Pharm Sci Tech. 2011;12(3):958-964. doi:10.1208/s12249-011-9647-5
23. Azevedo JR, Sizilio RH, Brito MB, et al. Physical and chemical characterization insulin-loaded chitosan-TPP nanoparticles. J Therm Anal Calorim. 2011;106: 685-689. doi:10.1007/s10973-011-1429-5
24. Dipiro JT, Wells T, Schwinghamer T. Pharmacotherapy Handbook. 5th ed. New York; 2005.
25. Rowe C, Sheskey PJ, Quinn ME, Reynald J. Handbook of Pharmaceutical Excipients. Sixth Edition. USA Pharmaceutical Press. Sixth Edit. USA: USA Pharmaceutical Press; 2009.
26. Bai JP, Hsu MJ, Shier WT. Insulin-Degrading Enzyme in A Human Colon Adenocarcinoma Cell Line (Caco-2). Pharm Res. 1995;12(4):513-517.
27. Pagare S, Bhatia M, Tripathi N, Pagare S, Bansal YK. Secondary metabolites of plants and their role : Overview Secondary Metabolites of Plants and their Role : Curr Trends Biotechnol Pharm. 2015;9(3): 293-304.
28. Buzea C, Pacheco II, Robbie K. Nanomaterials and nanoparticles: Sources and toxicity. Biointerphases. 2007;2(4):17-71. doi:10.1116/1.2815690
29. Jana U, Pal S, Mohanta GP, Manna PK, Manavalan R. Nanoparticles: A Potential Approach for Drug Delivery. Res J Pharm Technol. 2011;4(7): 1016-1019.
30. Debnath S, Kumar RS, Babu MN. Ionotropic Gelation – A Novel Method to Prepare Chitosan Nanoparticles. Res J Pharm Technol. 2011;4(4): 492-495.
31. Grenha A, Remu C. Microencapsulated chitosan nanoparticles for lung protein delivery. Eur J Pharm Sci. 2005; 25:427-437. doi: 10.1016/j.ejps.2005.04.009
32. Li X, Kong X, Shi S, et al. Preparation of Alginate Coated Chitosan Microparticles For Vaccine Delivery. BMC Biotechnol. 2008;8(89):1-11. doi:10.1186/1472-6750-8-89
33. Manikiran S., Pratap SN., Prasanthi N., Ramarao N. Formulation Perspectives of Chitosan: A Biomolecule for Microencapsulation. Res J Pharm Technol. 2011;4(5): 667-676.
34. Kannadasan M, Jain S., Roy R. Preparation and Biodegradation Study of Chitosan Copolymers to Colon Delivery. Res J Pharm Technol. 2014;7(12):1438-1440.
35. Prabhakar C, Krishna K. A Review on Polymeric Nanoparticles. Res J Pharm Technol. 2011;4(4): 496-498.
36. Bigucci F, Luppi B, Cerchiara T, et al. Chitosan / pectin polyelectrolyte complexes: Selection of suitable preparative conditions for colon-specific delivery of vancomycin. Eur J Pharm Sci. 2008; 5:435-441. doi: 10.1016/j.ejps.2008.09.004
37. Bhumkar DR, Pokharkar VB. Studies on Effect of pH on Cross-linking of Chitosan with Sodium Tripolyphosphate: A Technical Note. AAPS PharmSciTech. 2006;7(2): 2-7.
38. Jaiswal M, Lanjhiyana S. Fabrication and Evaluations of Dual Crosslinked Mesalamine containing Pectin-Chitosan gel micro beads for controlled and targeted colon delivery. Res J Pharm Technol. 2018;11(11): 4797-4804.
39. Kothule KU, Kesharwani P, Gidwani SK, Gide P. Development and Characterization of Chitosan Nanoparticles and Improvement of Oral Bioavailability of Poorly Water-Soluble Acyclovir. Res J Pharm Technol. 2010;3(4): 1241-1245.
40. Banker GS, Siepmann J, Rhodes C. Modern Pharmaceutics. CRC Press; 2002.
41. Mohanraj VJ, Chen Y. Nanoparticles – A Review. Trop J Pharm Res. 2006;5(June):561-573.
42. Yadav P, Pandey P, Parashar S, Neeta. Pectin as Natural Polymer: An overview. Res J Pharm Technol. 2017;10(4):1225-1229.

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