Porous Silicon Microparticles Enable Sustained Release of GLP‐1R Agonist Peptides for the Treatment of Type 2 Diabetes

Abstract

AbstractGLP‐1R agonist peptides play a prominent role in the treatment of type 2 diabetes. However, these peptides often suffer from short plasma half‐life, rapid clearance, and low in vivo chemical stability; requiring higher dosages and frequent administration. Although some peptides can be modified to improve these properties, such modification may lead to lower potency and immunogenicity. Here, a subcutaneously (SC) administrable porous silicon microparticle (pSiMP) platform for the sustained release of GLP‐1R agonist peptides is reported. The proof‐of‐concept involves using FDA‐approved exenatide, a potent GLP‐1R agonist, showcasing the platform's efficacy for therapeutic GLP‐1R peptides. pSiMPs with tailored particle size, pore dimensions, and surface chemistry unlock the potential for optimized loading and release of this peptide. The positively charged pSiMPs, with a pore diameter of 8 ± 3 nm, show an impressive loading capacity of 338 ± 42 µg mg−1 (exenatide/pSiMP). This optimized pSiMP formulation demonstrates extended and sustained exenatide release over 2 weeks in a bespoke in vitro SC tissue model. Notably, the pSiMP platform shields the peptide payload from proteolysis. In a mouse model, the SC‐injected formulation exhibits sustained in vivo release of exenatide in plasma for up to 2 weeks.