摩擦辅助结合凝胶促进阿仑膦酸钠透皮给药性能研究

Enhancement of transdermal delivery performance of alendronate sodium by friction assistance combined with gel formulation

摘要

目的 探讨摩擦辅助与凝胶剂型对阿仑膦酸钠(ALN)透皮给药性能的协同增效作用。方法 以卡波姆940为基质制备ALN凝胶,采用Franz扩散池法比较其与液体制剂的透皮行为;利用扫描电镜(SEM)及能谱(EDS)分析皮肤微观结构与药物分布;系统研究摩擦方式、时间及压力对ALN渗透的调控作用,并拟合透皮动力学模型。结果 凝胶制剂在载药量低于液体制剂的条件下,24 h累积透皮量与之相当;摩擦辅助可显著增强ALN渗透,砂纸摩擦组12 h累积透过量较无摩擦组提高约1.5倍。透皮动力学拟合表明,无摩擦时药物释放符合Higuchi模型(Fick扩散),而摩擦辅助后更符合Ritger-Peppas模型(扩散与溶蚀协同机制)。在优化条件(电动牙刷、100 g压力、10 min)下,凝胶与摩擦协同可显著提升透皮效率。SEM及EDS分析证实摩擦促进了药物在皮肤中的渗透与分布。结论 凝胶基质可通过“储库效应”实现与液体制剂相当的透皮递送能力;摩擦辅助能调节皮肤屏障功能,与凝胶的缓释特性形成互补。本研究构建的“摩擦-凝胶”协同递送策略,为ALN的局部靶向治疗提供了一种新颖、有效的增效方案。

Abstract

Objective To investigate the synergistic enhancement effect of friction assistance and gel formulation on the transdermal delivery performance of alendronate sodium (ALN). Methods ALN gel was prepared using carbomer 940 as the matrix.The transdermal behavior of the gel was compared with that of a liquid formulation using the Franz diffusion cell method.Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) were employed to analyze skin microstructure and drug distribution.The effects of friction method,duration,and pressure on ALN penetration were systematically studied,and transdermal kinetic models were fitted. Results Despite having a lower drug loading,the gel formulation achieved a 24-hour cumulative transdermal amount comparable to that of the liquid formulation.Friction assistance significantly enhanced ALN penetration,with the sandpaper friction group showing approximately a 1.5-fold increase in 12-hour cumulative permeation compared with the no-friction group.Kinetic fitting indicated that drug release followed the Higuchi model (Fickian diffusion) in the absence of friction,whereas it better conformed to the Ritger-Peppas model (diffusion-erosion synergistic mechanism) after friction assistance.Under optimized conditions (electric toothbrush, 100 g pressure,10 min),the combination of gel and friction significantly improved transdermal efficiency.SEM and EDS analyses confirmed that friction promoted drug penetration and distribution within the skin. Conclusion The gel matrix can achieve transdermal delivery capability comparable to that of the liquid formulation through a “reservoir effect.” Friction assistance modulates skin barrier function and complements the sustained-release characteristics of the gel.The “friction-gel” synergistic delivery strategy developed in this study provides a novel and effective approach for enhancing the local targeted therapy of ALN.

关键词

骨质疏松症 / 阿仑膦酸钠 / 透皮给药 / 摩擦辅助 / 累积透过量

Key words

Osteoporosis / ALN / Transdermal administration / Friction assisted / Accumulated penetration rate

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基金资助

山东省自然科学基金(ZR2023MH018);济宁医学院高层次科研项目培育计划(JYGC2022KJ007)