Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
Department of Chemistry, Panjab University, Chandigarh, Punjab, 160014, India.
AAPS PharmSciTech. 2024 Oct 1;25(7):229. doi: 10.1208/s12249-024-02945-0.
The development of effective therapy is necessary because the patients have to contend with long-term therapy as skin fungal infections usually relapse and are hardly treated. Despite being a potent antifungal agent, luliconazole (LCZ) has certain shortcomings such as limited skin penetration, low solubility in aqueous medium, and poor skin retention. Solid Lipid Nanoparticles (SLNs) were developed using biodegradable lipids by solvent injection method and were embodied into the gel base for topical administration. After in-vitro characterizations of the formulations, molecular interactions of the drug with excipients were analyzed using in-silico studies. Ex-vivo release was determined in contrast to the pure LCZ and the commercial formulation followed by in-vivo skin localization, skin irritation index, and antifungal activity. The prepared SLNs have an average particle size of 290.7 nm with no aggregation of particles and homogenous gels containing SLNs with ideal rheology and smooth texture properties were successfully prepared. The ex-vivo LCZ release from the SLN gel was lower than the commercial formulation whereas its skin deposition and skin retention were higher as accessed by CLSM studies. The drug reaching the systemic circulation and the skin irritation potential were found to be negligible. The solubility and drug retention in the skin were both enhanced by the development of SLNs as a carrier. Thus, SLNs offer significant advantages by delivering long lasting concentrations of LCZ at the site of infection for a complete cure of the fungal load together with skin localization of the topical antifungal drug.
因为皮肤真菌感染通常会复发且难以治疗,所以需要开发有效的治疗方法。尽管卢立康唑(LCZ)是一种有效的抗真菌药物,但它也存在一些缺点,如皮肤穿透性有限、在水介质中的溶解度低以及皮肤滞留性差。固体脂质纳米粒(SLN)是通过溶剂注入法用可生物降解的脂质开发的,并被嵌入到局部给药的凝胶基质中。在对制剂进行体外特性评估后,使用计算机模拟研究分析了药物与赋形剂的分子相互作用。与纯 LCZ 和市售制剂相比,测定了体外释放情况,随后进行了体内皮肤定位、皮肤刺激性指数和抗真菌活性测定。所制备的 SLN 的平均粒径为 290.7nm,没有粒子聚集,并且成功制备了含有 SLN 的均匀凝胶,具有理想的流变学和光滑的质地特性。通过 CLSM 研究发现,从 SLN 凝胶中释放的 LCZ 低于市售制剂,但其皮肤沉积和皮肤滞留更高。通过计算机模拟研究发现,到达体循环的药物量和皮肤刺激性潜力可以忽略不计。通过开发 SLN 作为载体,可以提高药物的溶解度和在皮肤中的滞留性。因此,SLN 提供了显著的优势,能够在感染部位持续释放长时间的 LCZ 浓度,从而彻底清除真菌负荷,并使局部抗真菌药物在皮肤中定位。
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