研製具有局部性之5-aminolevulinic acid微脂粒及其對皮膚疾病之光動力療效評估

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Photodynamic therapy with 5-aminolevulinic acid (ALA) is a non-invasive technique which an alternative therapy for many skin disease. Indeed, ALA is a precursor of the photosensitizer, protoporphyrin IX (PpIX), formed in vivo after the exogenous application of ALA. When PpIX is activated by light, photochemical reaction may cause malignant and non-malignant tissue to be destroyed. However, ALA molecules are zwitterions which have the limitation of poor penetration through cell membrane or skin. The properly design-carrier including liposome and ethosome was used to improve the penetration problem for topical delivery ALA. The physicochemical properties including particle size, zeta potential, drug entrapment and particle aggregation were used to choose an adequate carrier. The safety of carrier was evaluated with regard to cellular cytotoxicity and erythrocyte hemolysis. Accordingly, the release rates and skin penetration of ALA from carriers to examine the penetration behavior. The images from confocal laser scanning microsopy (CLSM) were observed for confirming the potency and deliver depth of the skin. Further, we used the platform of skin hyperproliferation and pre-cancer skin model to evaluate the skin penetration behavior of carriers. The study presents physicochemical properties and penetration behavior between liposome and ethosome. The result showed that the vesicle size of the ethosomal system significantly smaller than that of liposomal system. Moreover, our findings indicated that a molar ratio of 2:1:2.5 phosphatidylcholine/cholesterol/sodium stearate represented high entrapment efficiencies in both the ethosomal and liposomal systems. In addition, results of CLSM indicated that the penetration ability of ethosomes was grater than that of liposomes in terms of PpIX deposition in the normal skin. However, there was no correlation between the entrapment efficiencies and penetration of PpIX into skin. We also confirmed that PE ethosomal carrier significantly improved the delivery of ALA and the formation of PpIX in both normal skin and epidermal hyperplasia, and the TNF-α level was reduced after the ALA-ethosomes were applied to treat psoriasis.