Temperature-sensitive gel-loaded composite nanomedicines for the treatment of cervical cancer by vaginal delivery.

Abstract

In this study, toad venom (TV) and realgar were loaded into a poloxamer 188/407 (F127/F188)-based temperature-sensitive in situ gel (TISG) and encapsulated in solid lipid nanoparticles (TV-SLN) or ground nano-realgar (NR) to improve drug release and reduce local irritation after vaginal administration. The combination of TV-SLN and NR (TV-SLN/NR) greatly enhanced the inhibition of tumor cell proliferation and was most effective at a dose ratio of 2:3 (w/w). After TV-SLN/NR treatment, S and G0/G1 phase arrest were observed in HeLa and SKOV-3 cells and the inhibitory effects on proliferation were stronger than those in the conventional powder group. The gelation temperature of TV-SLN and NR-loaded TISG (TV-SLN/NR-TISG) using the selected formulation was 33±0.91°C. The cumulative release of the drug increased as the dissolution of gel progressed, showing a linear relationship (r>0.99). TV-SLN/NR-TISG enabled the sustained release of cargo by adhesion to the vaginal mucosa and showed excellent biocompatibility during continuous administration for 7days. We specifically demonstrated the effectiveness of the TISG for the vaginal delivery of TV-SLN and NR, supporting its important clinical implications for the treatment of cervical cancer.