Net-Neutral Nanoparticles-Extruded Microcapsules for Oral Delivery of Insulin.

Abstract

Oral delivery of insulin could widely improve the quality of life of diabetic patients but still requires further exploration. Commonly utilized oral delivery vehicles hardly penetrate the intestinal mucus barrier, thus greatly hurdling their therapeutic efficacy. State-of-the-art technology shows that coating particles with neutral surface charge could reduce adsorption of mucins and improved the transport of particles within mucus. However, the synthesis of net-neutral particles (NNs) usually need complex purification and processing procedure. Herein, the NNs were conveniently constructed by simply adjusting the ratio of positive (chitosan) and negative (γ-glutamic acid) materials. To further achieve the optimal bioavailability of NNs, NNs formed materials were package in to wild chrysanthemum pollens, obtaining pH-triggered nanoparticles-extruding microcapsules (PNMs@insulin). At the small intestine pH value (∼6.0), the amino groups of CS deprotonate gradually and trigger the swelling, followed by the rapid extrusion of NNs through nano-orifices on the pollens' surface. After oral administration of the microcapsules, plasma insulin levels were enhanced significantly with a high oral bioavailability of >40%, leading to a remarkable and longer-sustained blood glucose-reducing effect. Moreover, we discovered that the empty pollen shells could act as a potential saccharide-adsorbing agent, which helps to manage sugar intake. This oral strategy of insulin will provide a vast potential for daily and facile diabetes treatment.