Development of a novel method for the preparation of submicron particles based on thiolated chitosan.

It was the aim of this study to develop a simple method for the production of thiolated chitosan particles without being ionically crosslinked. In the first step, thiolated chitosan was ionically gelated with tripolyphosphate (TPP) and sulphate in aqueous solution forming submicron particles and microparticles, respectively. In the next step, thiol groups in and on the particles were partially oxidized forming stabilizing inter- and intramolecular disulfide bonds. As the degree of oxidation can be controlled during the production process, the share of thiol and disulfide groups can be adjusted on demand. Thereafter the polyanions were removed. Utilizing this novel preparation method stable particles of a mean size of 366 +/- 30 nm and a zeta potential of around + 11.3 +/- 1.3 mV can be produced using TPP as ionic crosslinker. On average 83% of all thiol groups were oxidized. In contrast, particles did not remain stable after removing sulphate as temporary auxiliary ionic crosslinker. Neither ionically nor covalently crosslinked particles were degraded by lysozyme under physiological conditions. Utilizing the novel method described here allows a simple production of thiolated chitosan particles without losing the cationic charge of chitosan.