Physicochemical behavior and cytotoxic effects of p(methacrylic acid–g-ethylene glycol) nanospheres for oral delivery of proteins

Abstract

The challenges faced to orally deliver therapeutic agents with unfavorable physicochemical properties, such as proteins, have been the primary motivation for the design and development of novel oral delivery systems that could circumvent biological barriers. In this work, we examined complexation-sensitive hydrogel nanospheres composed of poly[methacrylic acid–grafted-poly(ethylene glycol)] (P(MAA–g-EG)), on a model biological environment. For this purpose, a gastrointestinal cell culture model, the Caco-2 cell line, was employed to investigate the cytotoxic effects of the polymeric carrier and its effects on the cell monolayer integrity. The determination of the cytotoxic effects of the polymer network on the cell monolayer was performed by a colorimetric assay and by the counting of viable cells using the trypan blue exclusion method. Electrophysiological measurements were performed to measure the transepithelial electrical resistance changes in the monolayers in the presence and absence of the nanosphere suspension. The examination of the physicochemical interactions of the P(MAA–g-EG) nanosphere system with Caco-2 cell monolayers revealed that these systems possessed low cytotoxicity and were capable of opening the tight junctions between epithelial cells, therefore significantly reducing the transepithelial electrical resistance.