Ordiz Ignacio, Vega José A, Martín-Sanz Raquel, García-Suárez Olivia, Del Valle Miguel E, Feito Jorge
Departamento de Morfología y Biología Celular, Universidad de Oviedo, 33006 Oviedo, Spain.
Grupo SINPOS, Universidad de Oviedo, 33006 Oviedo, Spain.
Pharmaceutics. 2021 Nov 26;13(12):2016. doi: 10.3390/pharmaceutics13122016.
Transdermal delivery can be accomplished through various mechanisms including formulation optimization, epidermal stratum corneum barrier disruption, or directly by removing the stratum corneum layer. Microneedling, electroporation, a combination of both and also the intradermal injection known as mesotherapy have proved efficacy in epidermal-barrier disruption. Here we analyzed the effects of these methods of epidermal-barrier disruption in the structure of the skin and the absorption of four compounds with different characteristics and properties (ketoprofen, biotin, caffein, and procaine). Swine skin (Pietrain x Durox) was used as a human analogue, both having similar structure and pharmacological release. They were biopsied at different intervals, up to 2 weeks after application. High-pressure liquid chromatography and brightfield microscopy were performed, conducting a biometric analysis and measuring histological structure and vascular status. The performed experiments led to different results in the function of the studied molecules: ketoprofen and biotin had the best concentrations with intradermal injections, while delivery methods for obtaining procaine and caffein maximum concentrations changed on the basis of the lapsed time. The studied techniques did not produce significant histological alterations after their application, except for an observed increase in Langerhans cells and melanocytes after applying electroporation, and an epidermal thinning after using microneedles, with variable results regarding dermal thickness. Although all the studied barrier disruptors can accomplish transdermal delivery, the best disruptor is dependent on the particular molecule.
经皮给药可通过多种机制实现，包括制剂优化、破坏表皮角质层屏障或直接去除角质层。微针疗法、电穿孔、两者结合以及称为中胚层疗法的皮内注射已被证明在破坏表皮屏障方面具有疗效。在此，我们分析了这些破坏表皮屏障的方法对皮肤结构以及四种具有不同特性和性质的化合物（酮洛芬、生物素、咖啡因和普鲁卡因）吸收的影响。猪皮（皮特兰猪×杜洛克猪）被用作人类皮肤的类似物，二者具有相似的结构和药物释放特性。在给药后的不同时间间隔进行活检，最长至2周。进行了高压液相色谱分析和明场显微镜检查，开展了生物特征分析并测量了组织结构和血管状态。所进行的实验在研究分子的功能方面得出了不同结果：皮内注射时酮洛芬和生物素的浓度最佳，而获取普鲁卡因和咖啡因最大浓度的给药方法则随时间变化。除了电穿孔后观察到朗格汉斯细胞和黑素细胞增加，以及使用微针后表皮变薄，且真皮厚度结果不一外，所研究的技术在应用后未产生明显的组织学改变。尽管所有研究的屏障破坏方法都可实现经皮给药，但最佳的破坏方法取决于特定的分子。
