Thiomer nanoparticles: Stabilization via covalent cross-linking

The purpose of this study was the development of stable thiomer nanoparticles for mucosal drug delivery. Chitosanthioglycolic acid (chitosan-TGA) nanoparticles (NP) were formed via ionic gelation with tripolyphosphate (TPP). In order to stabilize the NP inter-and intra-molecular disulfide bonds were formed via controlled oxidation with hydrogen peroxide (H(2)O(2)). Thereafter, stability was investigated in saline and simulated body fluids at pH 2 and pH 5.5 via optical density measurements. The mucoadhesive properties were evaluated in vitro on freshly excised porcine intestinal mucosa via the rotating cylinder method. Particles had a mean size of 158 +/- 8 nm and a zeta potential of similar to + 16 mV. Three different degrees of oxidation were adjusted by the addition of H(2)O(2) in final concentrations of 10.60 mu mol (chitosan-TGA (ox1)), 21.21 mu mol (chitosan-TGA (ox2)), and 31.81 mu mol (chitosan-TGA (ox3)) leading to 60%, 75%, and 83% of oxidized thiol groups, respectively. More than 99% of chitosan-TGA (ox3) NP, 70% of chitosan-TGA (ox2) NP, and 50% of chitosan-TGA (ox1) NP were stable over a 60-min period in simulated gastric fluid. In contrast, only 10% of unmodified chitosan and chitosan-TGA NP which were just ionically cross-linked remained stable in the same experiment. The adhesion times of covalently cross-linked chitosan-TGA (ox1), chitosan-TGA (ox2), and chitosan-TGA (ox3) were similar to 41-fold, 31-fold, and 25-fold longer in comparison to unmodified ionically cross-linked chitosan. The method described here might be useful for the preparation of stable nanoparticulate drug delivery systems.