Fresno Contreras M J, Jiménez Soriano M M, Ramírez Diéguez A
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Alcalá University, E-28871 Alcalá de Henares, Madrid, Spain.
Int J Pharm. 2005 Jun 13;297(1-2):134-45. doi: 10.1016/j.ijpharm.2005.03.018. Epub 2005 Apr 26.
The objective of this study was to design an all-trans retinoic acid (RA) topical release system that modifies drug diffusion parameters in the vehicle and the skin in order to reduce systemic absorption and the side-effects associated with topical application of the drug to skin. Three cases of application of hydrogels containing RA either in free form or encapsulated in stratum corneum lipid liposomes (SCLLs) have been considered. For this purpose, we have evaluated the RA in formulations with combinations of Carbopol Ultrez 10 (U10) and hyaluronic acid (HA) for percutaneous absorption. In vitro permeability experiments with [3H]-t-RA were carried out using a Franz-type diffusion cell in abdominal rat skin samples. Accumulation of the drug in the surface and skin layers was evaluated by both the tape stripping method and a dissection technique, and subsequently, all the radiolabelled samples were analyzed by liquid scintillation counting. The results show that RA encapsulation not only prolongs drug release but also promotes drug retention by the viable skin. At the same time, interaction between RA and HA has an obstructive effect on diffusion, which contributes to the formation of a reservoir of the latter.
本研究的目的是设计一种全反式维甲酸（RA）局部释放系统，该系统可改变药物在载体和皮肤中的扩散参数，以减少全身吸收以及与药物局部应用于皮肤相关的副作用。已经考虑了三种应用含游离形式或包裹在角质层脂质脂质体（SCLL）中的RA的水凝胶的情况。为此，我们评估了含卡波姆优特雷斯10（U10）和透明质酸（HA）组合的制剂中RA的经皮吸收情况。使用弗兰兹型扩散池对腹部大鼠皮肤样本进行了[3H]-全反式维甲酸的体外渗透实验。通过胶带剥离法和解剖技术评估药物在表皮和皮肤层中的蓄积情况，随后，通过液体闪烁计数法对所有放射性标记样本进行分析。结果表明，RA包封不仅延长了药物释放，还促进了活性皮肤对药物的保留。同时，RA与HA之间的相互作用对扩散有阻碍作用，这有助于形成HA储库。
