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负载卢立康唑的溶致液晶纳米粒经皮给药系统:基于 QbD 的优化、体外评价和皮肤药动学评估。

Luliconazole loaded lyotropic liquid crystalline nanoparticles for topical delivery: QbD driven optimization, in-vitro characterization and dermatokinetic assessment.

机构信息

Industrial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani, Rajashthan, India.

Industrial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani, Rajashthan, India.

出版信息

Chem Phys Lipids. 2021 Jan;234:105028. doi: 10.1016/j.chemphyslip.2020.105028. Epub 2020 Dec 10.

DOI:10.1016/j.chemphyslip.2020.105028
PMID:33309940
Abstract

Fungal infections are an important cause of morbidity and pose a serious health concern especially in immunocompromised patients. Luliconazole (LUL) is a topical imidazole antifungal drug with a broad spectrum of activity. To overcome the limitations of conventional dosage forms, LUL loaded lyotropic liquid crystalline nanoparticles (LCNP) were formulated and characterized using a three-factor, five-level Central Composite Design of Response Surface Methodology. LUL loaded LCNP showed particle size of 181 ± 12.3 nm with an entrapment efficiency of 91.49 ± 1.61 %. The LUL-LCNP dispersion in-vitro drug release showed extended release up to 54 h. Ex-vivo skin permeation studies revealed transdermal flux value (J) of LUL-LCNP gel (7.582 μg/h/cm) 2 folds higher compared to marketed cream (3.3706 μg/h/cm). The retention of LUL in the stratum corneum was ∼1.5 folds higher and ∼2 folds higher in the epidermis and other deeper layers in comparison to the marketed cream. The total amount of drug penetrated (AUC) with LCNP formulation was 4.7 folds higher in epidermis and 6.5 folds higher in dermis than marketed cream. The study's findings vouch that LCNP can be a promising and effective carrier system for the delivery of antifungal drugs with enhanced skin permeation.

摘要

真菌感染是发病率的一个重要原因,特别是在免疫功能低下的患者中,是一个严重的健康问题。卢立康唑(LUL)是一种具有广谱活性的局部咪唑类抗真菌药物。为了克服传统剂型的局限性,采用三因素五水平的响应面法中心组合设计,对卢立康唑进行了载药溶致液晶纳米粒(LCNP)的配方和特性研究。载药 LCNP 的粒径为 181±12.3nm,包封率为 91.49±1.61%。LUL-LCNP 分散体的体外药物释放显示出长达 54 小时的延长释放。离体皮肤渗透研究表明,LUL-LCNP 凝胶的透皮通量值(J)比市售乳膏高 2 倍(7.582μg/h/cm 2 )。与市售乳膏相比,LUL 在角质层中的保留量增加了约 1.5 倍,在表皮和其他深层组织中的保留量增加了约 2 倍。LCNP 制剂的累积药物透皮量(AUC)在表皮中是市售乳膏的 4.7 倍,在真皮中是市售乳膏的 6.5 倍。研究结果表明,LCNP 可以作为一种有前途的、有效的载药系统,用于提高抗真菌药物的皮肤渗透。

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