Tuesday, January 8, 2019

PLGA from PolySciTech used in development of oral exenatide formulation for diabetes treatment

Diabetes is a highly prevalent disease affecting roughly 30.3 million Americans, leading to nearly 79,000 deaths annually, making it the 7th leading cause of death (ADA, 2015 statistics). Exenatide is a GLP-1 (glucagon-like peptide-1) agonist used to treat type-2 diabetes. Exenatide’s poor bioavailability requires it to be administered as an injection. Since diabetes is a chronic disease, it is preferable for therapy to be easy for patients to self-administer such as an oral formulation (tablet or pill). Recently, researchers at Yantai University (China) used PLGA (Polyvivo AP081) from PolySciTech (www.polyscitech.com) to develop a nanoparticle-exenatide formulation to improve uptake across the intestine for better bioavailability. This research holds promise for improved treatment options for diabetes. Read more: Song, Yina, Yanan Shi, Liping Zhang, Haiyan Hu, Chunyan Zhang, Miaomiao Yin, Liuxiang Chu et al. "Synthesis of CSK-DEX-PLGA nanoparticles for oral delivery of exenatide to improve its mucus penetration and intestinal absorption." Molecular Pharmaceutics (2019). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.8b00809

“Abstract: Oral absorption of exenatide, a drug for type 2 diabetes treatment, can be improved by using nanoparticles (NPs) for its delivery. To improve the mucus penetration and intestinal absorption of exenatide, we designed a block copolymer, CSKSSDYQC-dextran-poly (lactic-co-glycolic acid) (CSK-DEX-PLGA), and used it for preparation of exenatide-loaded NPs. The functionalized exenatide-loaded NPs composed of CSK-DEX-PLGA were able to target intestinal epithelial cells and reduce the mucus-blocking effect of the intestine. Moreover, the CSK modification of DEX-PLGA was found to significantly promote the absorption efficiency of NPs in the small intestine, based on in vitro ligation of intestinal rings and examination of different intestinal absorption sites. Compared with DEX-PLGA-NPs (DPs), the absorption of CSK-DEX-PLGA-NPs (CDPs) was increased in the villi, allowing the drug to act on goblet-like Caco-2 cells through clathrin-, caveolin- and gap-mediated endocytosis. Furthermore, enhanced transport ability of CDPs was observed in a study on Caco-2/HT-29-MTX co-cultured cells. CDPs exhibited a prolonged hypoglycemic response with a relative bioavailability of 9.2% in diabetic rats after oral administration. In conclusion, CDPs can target small intestinal goblet cells and have a beneficial effect on oral administration of macromolecular peptides as a nanometer-sized carrier.”
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