4.6 Article

Insulin Release from NPH Insulin-Loaded Pluronic\ F127 Hydrogel in the Presence of Simulated Tissue Enzyme Activity

期刊

PROCESSES
卷 8, 期 10, 页码 -

出版社

MDPI
DOI: 10.3390/pr8101320

关键词

drug release; insulin; tissue enzymes; thermosensitive polymers; protein delivery

资金

  1. Nova Southeastern University, Health Professions Division Grant
  2. Jazan University through the Saudi Arabian Cultural Mission (SACM)

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Background: Despite the widespread use of newer basal insulins, Natural Protamine Hagedorn (NPH) insulin still represents a well-established basal formulation with its long history of use, featuring the native form of human insulin. However, NPH insulin exhibits an undesirable peak within hours after a single subcutaneous (s.c.) injection, which may lead to hypoglycemia followed by insufficient basal insulin delivery. This may be attributed to the s.c. enzyme activities degrading the protamine in NPH microcrystals. Methods: A thermogelling block copolymer Pluronic F127 (PF127) was utilized as a protective carrier for NPH microcrystals and as a modulator for insulin release from NPH. NPH insulin-loaded PF127 gel was prepared with varying concentrations of the polymer (15-25%) under mild conditions. The formulations were characterized for their gelling temperature, morphology, gel erosion, and in vitro insulin release, with trypsin concentrations up to 5 U/mL. Results: Scanning electron microscopy (SEM) showed that the integrity of NPH microcrystals was maintained after preparation. The burst release of insulin from NPH was significantly attenuated over the course of similar to 16h in the presence of PF127 with or without enzyme activity. Conclusion: NPH-PF127 successfully resisted the acceleration of NPH crystal dissolution and insulin release in vitro in the presence of protamine-degrading enzyme activity, warranting further testing.

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