Hybrid nano- and microparticles based on metal ion crosslinked biopolymers are promising carriers for the development of drug delivery systems with improved biopharmaceutical properties. In this work, dexamethasone phosphate-containing particles based on chondroitin sulfate and chitosan or diethylaminoethyl chitosan additionally crosslinked with Zn were prepared. Depending on the polycation/polyanion ratio in the system, anionic and cationic polyelectrolyte complexes (PECs) were obtained. The anionic Zn-containing and Zn-free PECs had sizes of 154 and 180 nm and ζ-potentials of -22.4 and -27.5 mV, respectively. The cationic Zn-containing and Zn-free PECs had sizes of 242 and 362 nm and ζ-potentials of 22.4 and 24.7 mV, respectively. The presence of Zn in the system significantly prolonged the release of dexamethasone phosphate from the hybrid polyelectrolyte particle. The resulting release profiles of dexamethasone phosphate were in agreement with the Peppas-Sahlin kinetic model, which considers the combined effects of Fickian diffusion and polymer chain relaxation on the drug release rate. It was shown that the prolongation of drug release was mainly due to swelling and relaxation of the Zn crosslinked polymers. The developed particles exhibited good mucoadhesive properties and pronounced anti-inflammatory activity, making them attractive candidates for biomedical applications.
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