Enhanced transdermal delivery of polydatin via a combination of inclusion complexes and dissolving microneedles for treatment of acute gout arthritis

摘要

Gout is a disease that affects quality of life and has economic implications. However, most patients with gout are not adequately managed due to the adverse effects of current medical treatments. This study was performed to investigate the transdermal delivery of polydatin via the combination of inclusion complexes and dissolving microneedles and the therapeutic effect of polydatin on the treatment of acute gout arthritis. In vitro cytotoxicity of polydatin on HaCaT cells was measured by a CCK-8 assay. The results showed that polydatin exerted less cytotoxicity compared to indomethacin and colchicine. The aqueous solubility of polydatin increased considerably to 124.47?mg/mL via the formation of polydatin/Hydroxypropyl-β-cyclodextrin inclusion complexes. The complexes loaded dissolving microneedles showed significant improvement for in vitro polydatin permeation compared to the absence of complexes. Pharmacodynamic studies indicated that the polydatin complexes-loaded dissolving microneedles had significant inhibitory effects on swelling of the ankle in the arthritic mice. Furthermore, compared to the oral colchicine treatment, the body weights of the polydatin-treated mice increased significantly during the treatment, which implied a lower toxicity of polydatin microneedles delivery. The overall results indicate that the combination of inclusion complexes with dissolving microneedles provides a potential route for treatment of acute gout arthritis by enhanced transdermal delivery of polydatin.