Pierre M B, Tedesco A C, Marchetti J M, Bentley M V
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av do Café s/n, CEP 14040-903, Ribeirão Preto, SP, Brasil.
BMC Dermatol. 2001;1:5. doi: 10.1186/1471-5945-1-5. Epub 2001 Aug 30.
Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is a skin cancer therapy that still has limitations due to the low penetration of this drug into the skin. We have proposed in this work a delivery system for 5-ALA based on liposomes having lipid composition similar to the mammalian stratum corneum (SCLLs) in order to optimize its skin delivery in Photodynamic Therapy (PDT) of skin cancers.
SCLLs were obtained by reverse phase evaporation technique and size distribution of the vesicles was determinated by photon correlation spectroscopy. In vitro permeation profile was characterized using hairless mouse skin mounted in modified Franz diffusion cell.
Size exclusion chromatography on gel filtration confirmed vesicle formation. SCLLs obtained by presented a degree of encapsulation of 5-ALA around 5.7%. A distribution of vesicle size centering at around 500 nm and 400 nm respectively for SCLLs and SCLLs containing 5-ALA was found. In vitro 5-ALA permeation study showed that SCLLs preparations presented higher skin retention significantly (p < 0.05) on the epidermis without SC + dermis, with a decreasing of skin permeation compared to aqueous solution.
The in vitro delivery performance provided by SCLLs lead to consider this systems adequate for the 5-ALA-PDT of skin cancer, since SCLLs have delivered 5-ALA to the target skin layers (viable epidermis + dermis) to be treated by topical PDT of skin cancer.
使用5-氨基酮戊酸(5-ALA)的光动力疗法(PDT)是一种皮肤癌治疗方法,但由于该药物对皮肤的低渗透性,该疗法仍存在局限性。在这项工作中,我们提出了一种基于脂质体的5-ALA递送系统,其脂质组成类似于哺乳动物角质层(SCLLs),以便在皮肤癌的光动力疗法(PDT)中优化其皮肤递送。
通过反相蒸发技术获得SCLLs,并通过光子相关光谱法测定囊泡的大小分布。使用安装在改良Franz扩散池中的无毛小鼠皮肤来表征体外渗透曲线。
凝胶过滤的尺寸排阻色谱法证实了囊泡的形成。所获得的SCLLs对5-ALA的包封率约为5.7%。发现SCLLs和含有5-ALA的SCLLs的囊泡大小分布分别以约500nm和400nm为中心。体外5-ALA渗透研究表明,SCLLs制剂在没有SC +真皮的表皮上具有显著更高的皮肤滞留率(p < 0.05),与水溶液相比,皮肤渗透率降低。
SCLLs提供的体外递送性能使得该系统被认为适用于皮肤癌的5-ALA-PDT,因为SCLLs已将5-ALA递送至皮肤癌局部PDT治疗的目标皮肤层(活表皮+真皮)。