Topical creams of piperine loaded lipid nanocarriers for management of atopic dermatitis: development, characterization, and in vivo investigation using BALB/c mice model

The aim of the research work was to investigate the efficacy of cream loaded with lipid nanocarriers (ethosomes) of piperine for the management of atopic dermatitis (AD) in comparison to conventional cream. Ethosomes of piperine were formulated with varying concentration of phosphatidylcholine and ethanol; and evaluated for entrapment efficiency (EE), sedimentation behaviour, vesicle size, zeta potential, in vitro drug release, and shape. Creams loaded with optimized ethosomal dispersion of piperine were formulated and evaluated for physicochemical parameters, ex vivo permeation and drug retention in skin layers. Similarly, conventional creams of piperine in the same concentrations were formulated and evaluated. The optimized ethosomal a conventional cream was evaluated for cytotoxicity using HaCat cell lines and in vivo on BALB/c mice model. The EE (%) and vesicle size was 74.30 ± 3.88% and 318.1 nm, respectively, for optimized ethosomal dispersion. The zeta potential was −32.6 mV and vesicles were spherical in shape. The ethosomal cream showed higher deposition in the epidermis and dermis. The creams were non-cytotoxic to HaCat cell lines. In comparison to the negative control, the ethosomal (0.1%) and conventional (0.125%) cream, both significantly decreased the ear and skin thickness, skin severity; and WBC, granulocytes, and IgE antibodies level in the BALB/c mice model. The efficacy of ethosomal cream was significantly higher than conventional cream as compared to tacrolimus (0.1%). Ethosomal cream of piperine showed good potential for the management of AD in comparison to conventional cream.

本研究旨在对比负载胡椒碱醇质体（ethosomes）的乳膏与传统乳膏，探究其用于特应性皮炎（AD）管理的疗效。本研究通过调整磷脂酰胆碱与乙醇的浓度制备胡椒碱醇质体，并对其包封率（EE）、沉降行为、囊泡粒径、ζ电位、体外释药特性及形态进行表征。制备负载优化后胡椒碱醇质体分散液的乳膏，并对其理化参数、离体透皮性能及皮肤各层药物滞留量进行评价。同时制备相同浓度的胡椒碱传统乳膏并开展相同评价。对优化后的醇质体乳膏与传统乳膏，分别采用HaCat细胞系开展体外细胞毒性评价，并通过BALB/c小鼠模型开展体内细胞毒性评价。优化后的醇质体分散液的包封率与囊泡粒径分别为74.30 ± 3.88%与318.1 nm，ζ电位为-32.6 mV，囊泡呈球形。醇质体乳膏在表皮与真皮层的药物沉积量更高。两款乳膏对HaCat细胞系均无细胞毒性。与阴性对照组相比，0.1%浓度的醇质体乳膏与0.125%浓度的传统乳膏均可显著降低BALB/c小鼠的耳与皮肤厚度、皮肤严重程度，以及白细胞、粒细胞与免疫球蛋白E（IgE）抗体水平。相较于0.1%他克莫司（tacrolimus）组，醇质体乳膏的疗效显著优于传统乳膏。综上，相较于传统乳膏，胡椒碱醇质体乳膏在特应性皮炎管理中具有良好应用潜力。