Development of podophyllotoxin-loaded nanostructured lipid carriers for the treatment of condyloma acuminatum

摘要

Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papillomavirus (HPV). Podophyllotoxin (POD), a cytotoxic compound, is able to effectively treat HPV; however, the severe irritation side effects of POD restrict its use as a treatment for CA. The aim of the present study was to construct novel POD-loaded nanostructured nanolipid carriers (POD-NLCs) and evaluate their physicochemical characteristics and cytotoxicity. POD-NLCs (0.5%) were prepared using emulsion-evaporation and low temperature-solidification methods with optimized conditions and preparations. Subsequently, the POD-NLCs were physicochemically characterized and their in vitro and in vivo release efficiencies and in vitro cytotoxicity were studied. The prepared POD-NLCs had an average particle size, ζ potential, polydispersity index and encapsulation efficacy of 178.5±20 nm, −27±0.5 mV, 0.18±0.01 and 82.9±2%, respectively. In vitro and in vivo release studies demonstrated that POD-NLCs are able to provide sustained drug delivery for 72 h in vitro and 10 h in the mucosa. Compared with a tincture formulation of POD (POD-T), POD-NLC induced less inflammatory cytokine production in the cervical mucous and led to a decreased histopathological score. In addition, a cytotoxicity assay demonstrated that inhibition of the POD-NLCs was 98.4% at 24 h and remained >98% up to 72 h. Furthermore, more cells were arrested in the G2/M phase of the cell cycle following POD-NLC treatment compared with the POD-T treatment. The present study provides evidence that POD-NLC is a promising delivery system for the treatment of CA.