Topical psoralens plus ultraviolet A radiation (PUVA) therapy consists in the topical application of 8-methoxypsoralen (8-MOP) followed by the skin irradiation with ultraviolet A radiation. The employment of classical 8-MOP vehicles in topical PUVA therapy is associated with poor skin deposition and weak skin permeability of psoralens, thus requiring frequent drug administration. The aim of the present work was to formulate solid lipid nanoparticles (SLNs) able to increase the skin permeation of 8-MOP. For this purpose, the penetration enhancer Transcutol^® P (TRC) was added to the SLN formulation. SLNs were characterized with respect to size, polydispersity index, zeta potential, entrapment efficiency, morphology, stability, and biocompatibility. Finally, 8-MOP skin diffusion and distribution within the skin layers was investigated using Franz cells and newborn pig skin. Freshly prepared nanoparticles showed spherical shape, mean diameters ranging between 120 and 133 nm, a fairly narrow size distribution, highly negative ζ potential values, and high entrapment efficiency. Empty and loaded formulations were almost stable over 30 days. In vitro penetration and permeation studies demonstrated a greater 8-MOP accumulation in each skin layer after SLN TRC 2% and TRC 4% application than that after SLN TRC 0% application. Finally, the results of experiments on 3T3 fibroblasts showed that the incorporation of TRC into SLNs could enhance the cellular uptake of nanoparticles, but it did not increase their cytotoxicity.

中文翻译：

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含有SLN的Transcutol®P可改善8-甲氧基补骨脂素的皮肤递送

局部补骨脂素加紫外线A辐射（PUVA）疗法包括局部应用8-甲氧基补骨脂素（8-MOP），然后用紫外线A辐射皮肤。在局部PUVA疗法中使用经典的8-MOP载剂与补骨脂素的皮肤沉积不良和皮肤渗透性弱相关，因此需要频繁地给药。本工作的目的是配制能够增加8-MOP皮肤渗透性的固体脂质纳米颗粒（SLN）。为了这个目的，渗透增强剂TRANSCUTOL ^®将P（TRC）添加到SLN配方中。从尺寸，多分散指数，ζ电势，截留效率，形态，稳定性和生物相容性方面对SLN进行了表征。最后，使用Franz细胞和新生猪皮肤对8-MOP皮肤在皮肤层中的扩散和分布进行了研究。新鲜制备的纳米颗粒呈球形，平均直径在120至133 nm之间，尺寸分布相当窄，ζ电位值极负，并且包封率高。空载的配方在30天内几乎稳定。体外渗透和渗透研究表明，SLN TRC 2％和TRC 4％施用后，SLN TRC 0％施用后，每个皮肤层的8-MOP积累量更大。最后，