Ultrasound-Assisted Preparation of Exopolysaccharide/Nystatin Nanoemulsion for Treatment of Vulvovaginal Candidiasis

Ultrasound-Assisted Preparation of Exopolysaccharide/Nystatin Nanoemulsion for Treatment of Vulvovaginal Candidiasis
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超声辅助制备胞外多糖/制霉菌素纳米乳治疗外阴阴道念珠菌病

DOI:
10.2147/ijn.s241134
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发表时间:
2020-03
影响因子:
8
通讯作者:
Song Bo
Song Bo
中科院分区:
医学2区
文献类型:
--
作者:
Song Ruiteng;Yan Fang;Cheng Min;Dong Fakun;Lin Yongqi;Wang Yuzhen;Song Bo

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目的制霉菌素(NYS)是抗白色念珠菌(CA)和外阴阴道念珠菌病(VVC)的经典药物之一,但其水溶性差,易聚集。传统的NYS阴道递送制剂不完全适应阴道腔的特定环境。胞外多糖(EPS)在乳化剂中具有很大的应用潜力,但其在纳米乳液中的应用还未见报道。方法以EPS为乳化剂,液体石蜡油为油相,PEG 400为助乳化剂,NYS为载药物,采用超声法制备了EPS/NYS纳米乳(ENNE)。采用响应面法优化ENNE的制备工艺。优化后,进行体外和体内抗CA活性分析;动物实验;碘化丙啶(PI)、过碘酸-希夫(PAS)和苏木精-伊红(H&E)染色;细胞因子实验以研究对VVC的治疗能力。结果最佳制备工艺为:EPS含量1.5%,PEG 400含量3.2%,NYS含量700 μg/mL,石蜡油含量5.0%,超声时间15 min,超声振幅35%。ENNE显示出平均粒径为131.1 ± 4.32 nm的包封结构。ENNE具有高的储存和pH稳定性,以及缓慢释放。ENNE对CA的最低抑菌浓度(MIC)仅为0.125 μg/mL,抑菌圈为19.0 ± 0.5mm,显著提高了抗CA的作用。ENNE能破坏CA细胞膜,具有良好的体内抗CA作用和抗VVC作用。结论本研究结果将促进EPS在纳米技术中的应用,为治疗VVC提供新的有效的局部药物制剂。
Purpose As one of the classic anti-Canidia albicans (CA) and vulvovaginal candidiasis (VVC) drugs, nystatin (NYS) is limited by poor water solubility and easy aggregation. Traditional NYS vaginal delivery formulations do not fully adapt to the specific environment of the vaginal cavity. The use of exopolysaccharides (EPS) has great application potential in emulsifiers, but its use has not been reported in nanoemulsions. In this work, an EPS/NYS nanoemulsion (ENNE) was developed to improve the activities of NYS against CA and VVC Methods The ENNE was prepared by ultrasonic method using EPS as an emulsifier, liquid paraffin oil as an oil phase, PEG400 as a co-emulsifier, and NYS as the loaded drug. ENNE preparation was optimized by response surface method. After optimization, in vitro and in vivo analysis of the anti-CA activity; animal experiments; staining with propidium iodide (PI), periodic acid-schiff (PAS), and hematoxylin-eosin (H&E); and cytokine experiments were performed to investigate the therapeutic ability against VVC. Results The optimal formulation and preparation parameters of ENNE were determined as follows: EPS content of 1.5%, PEG400 content of 3.2%, NYS content of 700 μg/mL, paraffin oil content of 5.0%, ultrasonic time of 15 min, and ultrasonic amplitude of 35%. The ENNE showed an encapsulated structure with an average particle size of 131.1 ± 4.32 nm. ENNE exhibited high storage and pH stability, as well as slow release. The minimum inhibitory concentration (MIC) of ENNE against CA was only 0.125 μg/mL and the inhibition zone was 19.0 ± 0.5 mm, for greatly improved anti-CA effect. The prepared ENNE destroyed the membrane of CA cells, and exhibited good anti-CA effect in vivo and therapeutic ability against VVC. Conclusion The results of this study will promote the application of EPS in nanotechnology, which should lead to new and effective local drug formulations for treating VVC.
纳米颗粒和细胞渗透肽与皮肤的相互作用,以递送透皮药物。
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