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

开发载鬼臼毒素的纳米结构脂质载体用于治疗尖锐湿疣

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作者:Yan Gao, Kai Han, Qi Wang, Zhili Hu, Qingxiu Liu, Lishi Liu, Kang Zeng

Abstract

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.

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