Development of double-coated microparticles for improved oral insulin delivery in diabetes management

Purpose: To formulate double-coated insulin-loaded polymer-based microparticles (MPs) for oral delivery of insulin.

Methods: Different formulations of insulin-loaded MPs were prepared using polyethylene glycol 4000 (PEG 4000) and chitosan as primary coat and Eudragit® RL 100 as secondary coating agents. Physicochemical characterization, in vitro drug release, toxicological, and in vivo studies in diabetic rats were performed, and the results of the orally administered MPs were compared with those of subcutaneously administered Humulin®.

Results: The developed MPs showed good physicochemical characteristics. In vitro release studies showed that all batches of MPs exhibited sustained insulin release in 12 h with the highest insulin release achieved by MPs formulated using PEG 4000 as primary coating. In vivo, the orally administrated MPs containing 2 % chitosan achieved a reduction in blood glucose level from 100 mg/dL to 15.8 mg/dL after 10 h, compared to subcutaneously administered Humulin® which was 100 mg/dL to 20.60 mg/dL after 24 h. The MPs reduced blood urea (76.25 – 43.21 mg/dL) better than Humulin® (76.25 – 73.11 mg/dL), hence, may prevent development of insulin resistance and/or defective insulin release.

Conclusion: The effects of these formulations on blood glucose were comparable to subcutaneously administered Humulin® in diabetic rats. However, there is need to optimize these polymer blends for improved effectiveness, as well as study the long-term stability of these formulations.

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Materials

Humulin® 70/30 (Ely Lilly Pharmaceuticals Ltd), polyethylene glycol (PEG) 4000, chitosan (100, 000 KDa, with 85 – 95 % deacetylation; Wako Chemical Ltd, Japan), polyvinyl alcohol (PVA; Sigma-Aldrich, England), Phospholipon® 90G (P90G; Lipoid GmbH, Germany), Eudragit® RL 100, Poloxamer® 407 (P407; BDH, England), dichloromethane (DCM; Guangdong Sci-Tech Co. Ltd, China), alloxan monohydrate (Sigma Chemical Company, USA), Accu-Check® glucose meter (Roche Diabetes Care, Inc., USA). Other reagents utilized were of analytical grade and were used as procured without additional treatment.

Development of double-coated microparticles for improved oral insulin delivery in diabetes management, Josephat I Ogbonna, Mumuni A Momoh, Chinazom P Agbo, Hanifah Abdulmumin, Chinenye C Chukwu, John Alfa, Nafiu Aminu, James Oyeniyi, Umar S Okino, Franklin C Kenechukwu, Deghinmotei Alfred-Ugbenbo, Darlington C Youngson; Tropical Journal of Pharmaceutical Research February 2025; 24 (2): 141-151 ISSN: 1596-5996 (print); 1596-9827 (electronic) Available online at http://www.tjpr.org http://dx.doi.org/10.4314/tjpr.v24i2.2