Poly(ε-caprolactone)/eudragit nanoparticles for oral delivery of aspart-insulin in the treatment of diabetes

Nanoparticles prepared with a blend of a biodegradable polyester (poly(ε-caprolactone)) and a polycationic nonbiodegradable acrylic polymer (Eudragit® RS) have been used as a drug carrier for oral administration of a short-acting insulin analogue, aspart-insulin. Insulin-loaded nanoparticles, about 700 nm in diameter, encapsulated 97.5% of insulin and were able to release about 70% of their content in vitro in a neutral medium over 24 h. When administered orally to diabetic rats, insulin-loaded nanoparticles (50 IU/kg) decreased fasted glycemia for a prolonged period of time and improved the glycemic response to glucose in a time-dependent manner, with a maximal effect between 12 and 24 h after their administration. In parallel, plasma insulin levels increased. However, higher (100 IU/kg) and lower (25 IU/kg) doses of insulin did not exert any biological effect. It is concluded that polymeric nanoparticles composed of poly(ε-caprolactone)/Eudragit® RS are able to preserve the biological activity of the insulin analogue aspart-insulin; however, the postprandial peak suppression was prolonged more than 24 h by comparison with regular insulin working only 6-8 h. This effect may be explained by the monomeric configuration of aspart-insulin, which is probably better taken up by the intestinal mucosa than regular insulin. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:879-889, 2010