Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt.
Curr Drug Deliv. 2014;11(6):753-62. doi: 10.2174/1567201811666140605151923.
Sertaconazole nitrate is a broad spectrum imidazole antifungal agent with antibacterial and anti-inflammatory properties. However, its lipophilic nature and very poor aqueous solubility limit its use in the clinic. The aim of this study was to develop and characterize poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) polymeric nanomicelles for the solubilization and enhancement of sertaconazole antifungal activity. Sertaconazole was incorporated into PEG-b- PCL polymeric nanomicelles by a co-solvent evaporation method and micelle size, drug loading capacity and drug release properties were determined. The antifungal properties of nanomicelle-loaded drug were evaluated in Fusarium miscanthi, Microsporum canis, and Trichophyton mentagrophytes isolated, respectively from fungal keratitis, ringworm, and tinea corporis. PEG-b-PCL formed nanomicelles in aqueous solution with a diameter ranging from 40-80 nm, depending on the polymer composition and level of drug loading. Drug loading properties of the nanomicelles were dependent on the PCL block molecular weight and drug/polymer weight feed ratio. Drug encapsulation efficiency of up to 85% was achieved and this resulted in more than 80-fold enhancement in sertaconazole aqueous solubility at polymer concentration of 0.2%. Drug release studies showed an initial burst release followed by sustained drug release for 72 hours. In vitro antimycotic studies showed that nanomicelle-incorporated sertaconazole inhibited fungal growth in a concentration dependent manner. Further, it was more effective than the free drug in inhibiting the growth of Fusarium miscanthi and Microsporum canis. These results confirm the utility of PEG-b-PCL nanomicelles in enhancing the aqueous solubility and antifungal activity of sertaconazole or other similar antifungal drugs.
硝酸舍他康唑是一种具有广谱抗真菌作用的咪唑类抗真菌药物，具有抗菌和抗炎特性。然而，其亲脂性和极差的水溶性限制了其在临床上的应用。本研究旨在开发和表征聚乙二醇-聚（ε-己内酯）（PEG-b-PCL）聚合物胶束，以增溶和增强硝酸舍他康唑的抗真菌活性。采用共溶剂蒸发法将硝酸舍他康唑包载于 PEG-b-PCL 聚合物胶束中，测定胶束粒径、载药量和药物释放性能。评价了载药纳米胶束对分别从真菌性角膜炎、体癣和股癣中分离得到的拟茎点霉属、犬小孢子菌和须毛癣菌的抗真菌作用。PEG-b-PCL 在水溶液中形成纳米胶束，直径范围为 40-80nm，取决于聚合物组成和载药量。纳米胶束的载药性能取决于 PCL 嵌段分子量和药物/聚合物重量进料比。载药效率高达 85%，在聚合物浓度为 0.2%时，使硝酸舍他康唑的水溶解度提高了 80 多倍。药物释放研究表明，纳米胶束载药后有初始突释，随后持续释放 72 小时。体外抗真菌研究表明，纳米胶束载药后舍他康唑以浓度依赖的方式抑制真菌生长。此外，它比游离药物更能有效抑制拟茎点霉属和犬小孢子菌的生长。这些结果证实了 PEG-b-PCL 纳米胶束在提高硝酸舍他康唑或其他类似抗真菌药物的水溶性和抗真菌活性方面的应用。
