Pitzanti Giulia, Rosa Antonella, Nieddu Mariella, Valenti Donatella, Pireddu Rosa, Lai Francesco, Cardia Maria Cristina, Fadda Anna Maria, Sinico Chiara
Department of Life and Environmental Sciences, Unit of Drug Sciences, University of Cagliari, 09124 Cagliari, Italy.
Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Cagliari, Italy.
Pharmaceutics. 2020 Oct 15;12(10):973. doi: 10.3390/pharmaceutics12100973.
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.
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），随后用紫外线A辐射照射皮肤。在局部PUVA疗法中使用传统的8-MOP载体与补骨脂素的皮肤沉积不良和皮肤渗透性弱有关，因此需要频繁给药。本研究的目的是制备能够增加8-MOP皮肤渗透性的固体脂质纳米粒（SLN）。为此，将渗透促进剂二甲基亚砜（TRC）添加到SLN制剂中。对SLN的大小、多分散指数、zeta电位、包封率、形态、稳定性和生物相容性进行了表征。最后，使用Franz扩散池和新生猪皮肤研究了8-MOP在皮肤层中的扩散和分布。新制备的纳米粒呈球形，平均直径在120至133nm之间，粒径分布相当窄，ζ电位值高度为负，包封率高。空载体和载药制剂在30天内几乎稳定。体外渗透和透皮研究表明，与SLN TRC 0%给药后相比，应用2%和4%的SLN TRC后，各皮肤层中8-MOP的蓄积量更大。最后，对3T3成纤维细胞的实验结果表明，将TRC掺入SLN中可以增强纳米粒的细胞摄取，但不会增加其细胞毒性。
