A novel peptide nanomedicine for treatment of pancreatogenic diabetes

Abstract

Pancreatogenic diabetes (PD) is a potentially fatal disease that occurs secondary to pancreatic disorders. The current anti-diabetic therapy for PD is fraught with adverse effects that can increase morbidity. Here we investigated the efficacy of novel peptide nanomedicine: pancreatic polypeptide (PP) in sterically stabilized micelles (SSM) for management of PD. PP exhibits significant anti-diabetic efficacy but its short plasma half-life curtails its therapeutic application. To prolong and improve activity of PP in vivo, we evaluated the delivery of PP in SSM. PP-SSM administered to rats with PD, significantly improved glucose tolerance, insulin sensitivity and hepatic glycogen content compared to peptide in buffer. The studies established the importance of micellar nanocarriers in protecting enzyme-labile peptides in vivo and delivering them to target site, thereby enhancing their therapeutic efficacy. In summary, this study demonstrated that PP-SSM is a promising novel anti-diabetic nanomedicine and therefore should be further developed for management of PD.

From the clinical editor: Pancreatic peptide was earlier demonstrated to address pancreatogenic diabetes, but its short half-life represented major difficulties in further development for therapeutic use. PP-SSM (pancreatic polypeptide in sterically stabilized micelles) is a promising novel anti-diabetic nanomedicine that enables prolonged half-life and increased bioactivity of PP, as shown in this novel study, paving the way toward clinical studies in the near future.

Keywords: 1,2-Distearoyl-sn-glycero-3-phosphatidylethanolamine-N-[methoxy (polyethyleneglycol)-2000]; CP; Chronic pancreatitis; DPSPE-PEG(2000); EPR; Enhanced permeation and retention; GLP-1; GLUT4; GTT; Glucagon-like peptide -1; Glucose tolerance test; Glucose transporter 4; IST; Insulin sensitivity test; PBS; PD; PP; Pancreatic polypeptide; Pancreatogenic diabetes; Phosphate buffered saline; SEM; SSM; Standard error of mean; Sterically stabilized micelles; T3cDM; Type 3c diabetes mellitus; VIP; Vasoactive intestinal peptide.