Nanosized insulin-complexes based on biodegradable amine-modified graft polyesters poly[vinyl-3-(diethylamino)-propylcarbamate-co-(vinyl acetate)-co-(vinyl alcohol)]-graft-poly(l-lactic acid): Protection against enzymatic degradation, interaction with Cac

The protection capacity of NC and their interaction with Caco-2 cells varied strongly as a function of lactide-grafting (hydrophobicity). With increasing lactide-grafting (P(26) ⩽ P(26)-1LL ⩽ P(26)-2LL) NC protected up to 95% of the insulin against degradation by trypsin. Transport and uptake into cell monolayers increased with higher l-lactid grafting. About 25% of a 1.25 mg/ml TRITC-insulin NC dispersion with P(26)-2LL was recovered in Caco-2 cells after 90 min. A concentration dependent cytotoxicity profile was observed showing elevated LDH release and decreased TEER values. The cytotoxicity correlates with the surfactant like character of the polymers, decreasing the surface tension to 46 mN/m for the amphiphilic P(26)-2LL. The observed TEER decrease was reversible after 20 h, suggesting that the biodegradable comb-polyesters offer a promising approach to overcome mucosal barriers.