Oral hypoglycaemic effect of GLP-1 and DPP4 inhibitor based nanocomposites in a diabetic animal model

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• 作者：Neha Shrestha^a ; ^{neha.shrestha@helsinki.fi" class="auth_mail" title="E-mail the corresponding author} ; Francisca Araú ; jo^a ; ^b ; ^c ; Mohammad-Ali Shahbazi^a ; Ermei M&auml ; kil&auml ; ^d ; Maria Joã ; o Gomes^b ; ^c ; Mikko Airavaara^e ; Esko I. Kauppinen^f ; Janne Raula^f ; Jarno Salonen^d ; Jouni Hirvonen^a ; Bruno Sarmento^b ; ^g ; Hé ; lder A. Santos^a ; ^{helder.santos@helsinki.fi" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Glucagon-like peptide-1 ; Dipeptidyl peptidase-4 ; Porous silicon nanoparticles ; Oral delivery ; Chitosan ; In vivo ; Ex vivo
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 June 2016
• 年：2016
• 卷：232
• 期：Complete
• 页码：113-119
• 全文大小：1283 K

文摘

Glucagon-like peptide-1 (GLP-1), an incretin hormone, is used for type 2 diabetes mellitus (T2DM) treatment because of its ability to stimulate insulin secretion and release in a glucose-dependent manner. Despite of its potent insulinotropic effect, oral GLP-1 delivery is greatly limited by its instability in the gastrointestinal tract, poor absorption efficiency and rapid degradation by dipeptidylpeptidase-4 (DPP4) enzyme leading to a short half-life (~ 2 min). Thus, a multistage dual-drug delivery nanosystem was developed to deliver GLP-1 and DPP4 inhibitor simultaneously. The system comprised of chitosan-modified porous silicon (CSUn) nanoparticles, which were coated by an enteric polymer, hydroxypropylmethylcellulose acetate succinate MF, using aerosol flow reactor technology. A non-obese T2DM rat model induced by co-administration of nicotinamide and streptozotocin was used to evaluate the in vivo efficacy of the nanosystem. The oral administration of H-CSUn nanoparticles resulted in 32% reduction in blood glucose levels and ~ 6.0-fold enhancement in pancreatic insulin content, as compared to the GLP-1 + DPP4 inhibitor solution. Overall, these results present a promising system for oral co-delivery of GLP-1 and DPP4 inhibitor that could be further evaluated in a chronic diabetic study.