FORMULATION AND IN VITRO CHARACTERISATION OF GLUCOSE-RESPONSIVE NANOCAPSULES FOR THE DELIVERY OF M-INSULIN
Keywords:Diabetes, Insulin, Nanocapsules, Glucose responsive
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 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 hours.
Conclusion: The outcomes of the study demonstrated that the developed nanocapsules can be effectively used for glucose-responsive delivery of M-insulin.
Manorma, Mazumder R, Rani A, Budhori R, Kaushik A. Current measures against ophthalmic complications of diabetes mellitus-a short review. Vol. 13, International Journal of Applied Pharmaceutics. Innovare Academics Sciences Pvt. Ltd; 2021. p. 54–65.
Smith AG, Singleton JR. Diabetic Neuropathy. Continuum: Lifelong Learning in Neurology. 2012;18(1):60–84. doi: 10.1212/01.CON.0000411568.34085.3e.
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. et al. 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.
Schnell O, Cappuccio F, Genovese S, Standl E, Valensi P, Ceriello A. Type 1 diabetes and cardiovascular disease. Cardiovasc Diabetol. 2013;12(1):1–10. doi: 10.1186/1475-2840-12-156.
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;7:1–16. doi: 10.2174/2211738507666190321110721.
Horvath K, Jeitler K, Berghold A, Ebrahim SH, Gratzer TW, Plank J, et al. Long‐acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane database of systematic reviews. 2007(2).
Peterson GE. Intermediate and long-acting insulins: a review of NPH insulin, insulin glargine and insulin detemir. Current medical research and opinion. 2006 Dec 1;22(12):2613-9.
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. In: Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd; 2004.
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.
Iwaoka H, Makino H, Yoshida S. Continuous subcutaneous insulin infusion. Nippon rinsho Japanese journal of clinical medicine. 1989;47(11):2577–82.
Sze MN, May JE, Emmerson AJB. Continuous insulin infusion in hyperglycaemic extremely-low-birth-weight neonates: An evaluation of treatment response. Biol Neonate. 2005;87(4):269–72.
Pickup JC, Keen H, Parsons JA, Alberti KG. Continuous subcutaneous insulin infusion: an approach to achieving normoglycaemia. British Medical Journall. 1978;1(6107):204–7. doi: 10.1136/bmj.1.6107.204.
Wisniewski N, Moussy F, Reichert WM. Characterization of implantable biosensor membrane biofouling. Fresenius J Anal Chem. 2000;366(6):611–21.
Ma R, Shi L. Phenylboronic acid-based glucose-responsive polymeric nanoparticles: synthesis and applications in drug delivery. Polymer Chemistry. 2014;5(5):1503-18.
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.
Volpatti LR, Matranga MA, Cortinas AB, Delcassian D, Daniel KB, Langer R, Anderson DG. Glucose-Responsive Nanoparticles for Rapid and Extended Self-Regulated Insulin Delivery. ACS Nano. 2020 Jan 28;14(1):488–97.
Gu Z, Dang TT, Ma M, Tang BC, Cheng H, Jiang S, et al. Glucose-Responsive Microgels Integrated with Enzyme Nanocapsules for Closed-Loop Insulin Delivery. ACS Nano. 2013;7(8):6758–6766. doi: 10.1021/nn401617u.
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.
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 Res. 2021 Nov 15;81–8.
Jain N, Verma A. Preformulation studies of pilocarpine hydrochloride as niosomal gels for ocular drug delivery. Asian Journal of Pharmaceutical and Clinical Research. 2020 Apr 16;149–55.
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.
Jeong SY, Kim SW. Self-regulating Insulin Delivery Systems I. Synthesis and Characterization of Glycosylated Insulin. Journal of Controlled 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.
Shen B, Yang S, inventors. Composition and method for preparing alginate nanocapsules. United States patent US 8,449,919. 2013 May 28.
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.
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.
Singh S, Kushwaha AK, Vuddanda PR, Karunanidhi P, Singh SK. Development and evaluation of solid lipid nanoparticles of raloxifene hydrochloride for enhanced bioavailability. Biomed Res Int. 2013;1-9.
Prusty AK, Sahu SK. Development and Evaluation of Insulin Incorporated Nanoparticles for Oral Administration. ISRN Nanotechnology. 2013 Jul 15:1–6.
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. In: Procedia Engineering. Elsevier Ltd; 2017. p. 55–9.
Zohri M, Nomani A, Gazori T, Haririan I, Mirdamadi SS, Sadjadi SK, et al. Characterization of chitosan/alginate self-assembled nanoparticles as a protein carrier. J Dispers Sci Technol. 2011 Apr;32(4):576–82.
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.
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