Thiomer nanoparticles: Stabilization via covalent cross-linking

Abstract

The purpose of this study was the development of stable thiomer nanoparticles for mucosal drug delivery. Chitosan-thioglycolic 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 (H₂O₂). 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 ~ + 16 mV. Three different degrees of oxidation were adjusted by the addition of H₂O₂ in final concentrations of 10.60 µmol (chitosan-TGA (ox1)), 21.21 µmol (chitosan-TGA (ox2)), and 31.81 µmol (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 ~ 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.

Keywords::

• Thiolated chitosan
• nanoparticles
• stability
• mucoadhesion
• delivery system

Acknowledgment

This work was supported by the BFS project (Bayrische Forschungsstiftung) (ID 3084) and the Nano-Health project (No. 0200) as part of the Austrian Nano-Initiative being financed by the Austrian FFG (Forschungsförderungsgesellschaft mbH) (Project No. 819721).

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.