FORMULATION AND IN VITRO CHARACTERISATION OF GLUCOSE-RESPONSIVE NANOCAPSULES FOR THE DELIVERY OF M-INSULIN

Authors

  • NIKHAR VISHWAKARMA Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr Harisingh Gour University Sagar, M. P. 470003. India https://orcid.org/0000-0002-8031-4637
  • SURESH P. VYAS Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr Harisingh Gour University Sagar, M. P. 470003. India

DOI:

https://doi.org/10.22159/ijap.2023v15i1.46511

Keywords:

Diabetes, Insulin, Nanocapsules, Glucose responsive

Abstract

Objective: The present study aimed to develop and characterize Chitosan coated Alginate Nanocapsules loaded with M-Insulin Concanavalin A Complex for glucose-responsive delivery.

Methods: Preformulation studies were performed on the Insulin human recombinant and the Nanocapsules were prepared by the ionic gelation method and coated with chitosan using electrostatic attraction. The formulation variables were optimized using Box-Behnken design (BBD) with the help of Design-Expert® Software. Three independent variables taken were the concentration of chitosan (A1), the concentration of sodium alginate (A2), and the stirring rate (A3). The response variables selected were the average particle size (nm) (B1), polydispersity index (B2), and cumulative release (%) (B3).

Results: The results from the Preformulation studies indicated that the received sample of the Insulin human recombinant was pure. The optimized nanocapsules possessed an average particle size of 382.4 nm, PDI 0.211 and zeta potential of 30.25 mV. The entrapment efficiency was found to be 79.2 %. The nanocapsules were further characterized for their surface morphology using TEM and were found to be of regular shape. The in vitro drug release study indicated that the nanocapsules were able to release 58 % of M-insulin in hyperglycaemic conditions for 12 h.

Conclusion: The outcomes of the study demonstrated that the developed nanocapsules can be effectively used for glucose-responsive delivery of M-insulin.

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References

Manorma, Mazumder R, Rani A, Budhori R, Kaushik A. Current measures against ophthalmic complications of diabetes mellitus-a short review. Int J App Pharm. 2021;13:54-65. doi: 10.22159/ijap.2021v13i6.42876.

Smith AG, Singleton JR. Diabetic neuropathy. Continuum (Minneap Minn). 2012;18(1):60-84. doi: 10.1212/01.CON.0000411568.34085.3e. PMID 22810070.

Suma S, Abeetha S, Divya R. Estimation of serum magnesium levels and its correlation among patients with diabetic retinopathy. Int J Pharm Pharm Sci. 2022 Oct 1:43-5.

Thorn LM, Forsblom C, Fagerudd J, Thomas MC, Pettersson Fernholm K, Saraheimo M. Metabolic syndrome in type 1 diabetes: association with diabetic nephropathy and glycemic control (the FinnDiane study). Diabetes Care. 2005;28(8):2019-24. doi: 10.2337/diacare.28.8.2019, PMID 16043748.

Schnell O, Cappuccio F, Genovese S, Standl E, Valensi P, Ceriello A. Type 1 diabetes and cardiovascular disease. Cardiovasc Diabetol. 2013;12(1):156. doi: 10.1186/1475-2840-12-156, PMID 24165454.

Federation ID. International diabetes federation: IDF diabetes atlas. Brussels, Belgium; 2019.

Federation ID. International diabetes federation: IDF diabetes atlas. Brussels, Belgium; 2021.

Bahman F, Greish K, Taurin S. Nanotechnology in insulin delivery for management of diabetes. Pharm Nanotechnol. 2019;7(2):113-28. doi: 10.2174/ 2211738507666190321110721. PMID 30907328.

Horvath K, Jeitler K, Berghold A, Ebrahim SH, Gratzer TW, Plank J. Long‐acting insulin analogues versus NPH Insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007(2):CD005613. doi: 10.1002/14651858.CD005613.pub3, PMID 17443605.

Peterson GE. Intermediate and long-acting insulins: a review of NPH Insulin, insulin glargine and insulin detemir. Curr Med Res Opin. 2006 Dec 1;22(12):2613-9. doi: 10.1185/ 030079906X154178, PMID 17166343.

Siebenhofer A, Plank J, Berghold A, Narath M, Gfrerer R, Pieber T. Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003287. doi: 10.1002/14651858.CD003287.pub4

Rodrigues PA, Balan A, Purushothaman C. A prospective comparative observational study on safety, efficacy and cost-effectiveness of insulin and their analogues. Int J Pharm Pharm Sci. 2018 Jul 1;10(7):62. doi: 10.22159/ijpps.2018v10i7.21464.

Iwaoka H, Makino H, Yoshida S. Continuous subcutaneous insulin infusion. Nihon Rinsho. 1989;47(11):2577-82. PMID 2601069.

Ng SM, May JE, Emmerson AJ. Continuous insulin infusion in hyperglycaemic extremely low-birth-weight neonates. Biol Neonate. 2005;87(4):269-72. doi: 10.1159/000083863. PMID 15695923.

Pickup JC, Keen H, Parsons JA, Alberti KG. Continuous subcutaneous insulin infusion: an approach to achieving normoglycaemia. Br Med J. 1978;1(6107):204-7. doi: 10.1136/bmj.1.6107.204, PMID 340000.

Wisniewski N, Moussy F, Reichert WM. Characterization of implantable biosensor membrane biofouling. Fresenius J Anal Chem. 2000;366(6-7):611-21. doi: 10.1007/s002160051556, PMID 11225773.

Ma R, Shi L. Phenylboronic acid-based glucose-responsive polymeric nanoparticles: synthesis and applications in drug delivery. Polym Chem. 2014;5(5):1503-18. doi: 10.1039/C3PY01202F.

Vyas SP, Karajgi JS, Gogoi PJ, Jain NK. Development, characterization and evaluation of an auto-regulatory delivery system for insulin. J Microencapsul. 1991;8(2):235-42. doi: 10.3109/02652049109071491, PMID 1765903.

Volpatti LR, Matranga MA, Cortinas AB, Delcassian D, Daniel KB, Langer R. Glucose-responsive nanoparticles for rapid and extended self-regulated insulin delivery. ACS Nano. 2020 Jan 28;14(1):488-97. doi: 10.1021/acsnano.9b06395, PMID 31765558.

Gu Z, Dang TT, Ma M, Tang BC, Cheng H, Jiang S. Glucose-responsive microgels integrated with enzyme nanocapsules for closed-loop insulin delivery. ACS Nano. 2013;7(8):6758-66. doi: 10.1021/nn401617u, PMID 23834678.

Mody N, Sharma R, Vyas SP. Assessment of release kinetics of docetaxel loaded PLGA nanoparticles. Asian J Pharm Pharmacol. 2019 Jul;5(5):1031-7. doi: 10.31024/ajpp.2019.5.5.24.

United States Pharmacopeia. National formulary. Rockville, (MD): United States Pharmacopeial Commission; 2007.

Rani R, Kaur T, Singh AP, Singh AP. Formulation and evaluation of moronic acid-loaded transdermal patches. Int J Curr Pharm Sci 2021;13:81-8. doi: 10.22159/ijcpr.2021v13i6.1932.

Jain N, Verma A. Preformulation studies of pilocarpine hydrochloride as niosomal gels for ocular drug delivery. Asian J Pharm Clin Res. 2020 Apr 16:149-55. doi: 10.22159/ajpcr.2020.v13i6.37523.

Feldmeier HG, Rahn HW, Wolf I. Quantitative determination of crystallin insulin in insulin-zinc suspensions as an in-process control. Pharmazie. 1991 Jul 1;46(7):517-9. PMID 1784613.

Seo Young Jeong, Sung Wan Kimn, Eenink MJD, Feijen J. Self-regulating insulin delivery systems I. Synthesis and characterization of glycosylated insulin. J Control Release. 1984;1(1):57-66. doi: 10.1016/0168-3659(84)90021-X.

Gou Y, Geng J, Richards SJ, Burns J, Remzi Becer C, Haddleton DM. A detailed study on understanding glycopolymer library and con a interactions. J Polym Sci A Polym Chem. 2013;51(12):2588-97. doi: 10.1002/pola.26646, PMID 23761950.

Shen B, Yang S, Inventors. Composition and method for preparing alginate nanocapsules. United States Patent US. 2013 May 28;8(449):919.

Sarmento B, Ribeiro AJ, Veiga F, Ferreira DC, Neufeld RJ. Insulin-loaded nanoparticles are prepared by alginate ionotropic pre-gelation followed by chitosan polyelectrolyte complexation. J Nanosci Nanotechnol. 2007 Aug;7(8):2833-41. doi: 10.1166/jnn.2007.609, PMID 17685304.

El-Hussien D, El-Zaafarany GM, Nasr M, Sammour O. Chrysin nanocapsules with dual anti-glycemic and anti-hyperlipidemic effects: chemometric optimization, physicochemical characterization and pharmacodynamic assessment. Int J Pharm. 2021 Jan 5;592:120044. doi: 10.1016/j.ijpharm.2020.120044. PMID 33157212.

Kushwaha AK, Vuddanda PR, Karunanidhi P, Singh SK, Singh S. Development and evaluation of solid lipid nanoparticles of raloxifene hydrochloride for enhanced bioavailability. BioMed Res Int. 2013;2013:584549. doi: 10.1155/2013/584549. PMID 24228255.

Prusty AK, Sahu SK. Development and evaluation of insulin incorporated nanoparticles for oral administration. ISRN Nanotechnol. 2013 Jul 15;2013:1-6. doi: 10.1155/2013/591751.

Rahmawati R, Permana MG, Harison B, Yuliarto B, Kurniadi D. Optimization of frequency and stirring rate for synthesis of magnetite (Fe3O4) nanoparticles by using coprecipitation-ultrasonic irradiation methods. Procedia Eng. 2017:55-9.

Zohri M, Nomani A, Gazori T, Haririan I, Mirdamadi SS, Sadjadi SK. Characterization of chitosan/alginate self-assembled nanoparticles as a protein carrier. J Dispers Sci Technol. 2011 Apr;32(4):576-82. doi: 10.1080/01932691003757314.

Jelvehgari M, Barar J, Nokhodchi A, Shadrou S, Valizadeh H. Effects of process variables on micromeritic properties and drug release of non-degradable microparticles. Adv Pharm Bull. 2011;1(1):18-26. doi: 10.5681/apb.2011.003, PMID 24312752.

Published

07-01-2023

How to Cite

VISHWAKARMA, N., & VYAS, S. P. (2023). FORMULATION AND IN VITRO CHARACTERISATION OF GLUCOSE-RESPONSIVE NANOCAPSULES FOR THE DELIVERY OF M-INSULIN. International Journal of Applied Pharmaceutics, 15(1), 178–185. https://doi.org/10.22159/ijap.2023v15i1.46511

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