Impact of the in vitro gastrointestinal passage of biopolymer-based nanoparticles on insulin absorption

Abstract

Although the oral administration of insulin is recognized as the safest and most attractive, insulin oral bioavailability is usually reduced due to the susceptibility to acidic and enzymatic degradation in the gastrointestinal (GI) tract and intrinsic low intestinal permeability. Nanoencapsulation of insulin is, thus, foreseen as a promising approach to overcome most of these drawbacks. The effect of the GI environment on the aggregation of alginate/dextran sulfate-based nanometric-sized particles, uncoated or double-coated with chitosan and albumin, and its further influence on insulin release and permeability at the cellular level, was investigated in vitro. The swelling and aggregation behavior of NPs in gastric conditions was accompanied by the prevention of insulin release. In intestinal conditions, the fast dissolution of uncoated NPs was responsible for a wide size distribution and for a burst release of insulin, while the size stability provided by albumin/chitosan-coating led to sustained release. Chitosan/albumin-coated NPs were able to significantly increase the permeability of insulin across the cell-based engineered intestinal models, further enhanced by the presence of a mucus layer and M-like cells. The influence of these models on insulin permeability was compared to the curve that better adjusted to the mathematical kinetics of insulin release from these biopolymeric-NPs. Thus, a correlation between the size behavior of NPs upon passage in the GI tract and both insulin release profile and permeation across intestinal in vitro models was addressed. These results provide proof-of-concept evidence that the GI passage of NPs has a major influence on the oral absorption of macromolecules.