Physicochemical and safety evaluation of 5-aminolevulinic acid in novel liposomes as carrier for skin delivery.
In this study we successfully entrapped 5-aminolevulinic acid (ALA) in liposome, although it exists as a zwitter ion. A molar ratio of 2:1:2.5 phosphatidyle-thanolamine (PE)/cholesterol/sodium stearate represented the best condition to achieve high entrapment efficiency (29.37 +/- 1.21%), and the average vehicle size was 133.6 +/- 2.8 nm. After 32 days of storage, the vehicle sizes of formulations with PE series were still approximately less than 200 nm. The safety of liposomes was tested and ensured both with regard to cellular cytotoxicity and erythrocyte hemolysis. Safety studies showed that liposome formulations did not affect cell viability except when both potassium stearate and sodium oleate were added. Moreover, PE and PE/cholesterol did not damage human erythrocytes in this study. The range of the hemolytic effect caused by liposomes was 5 to 37% and the effect was dependent on the amount of sodium stearate added to the formulation. According to the release rates and skin penetration of ALA liposomes in vitro, PE/cholesterol/sodium stearate liposomes might increase skin penetration, and it was shown that penetration across the stratum-corneum (sc) layer was the rate-limiting process. Images from confocal laser scanning microscopy (CLSM) confirmed the great potency of liposomes for delivering ALA into skin.
Fang
Yi-Ping
YP
Graduate Institute of Pharmaceutical Sciences, College of Pharmacy, Kaohsiung Medical University, Taiwan.
Wu
Pao-Chu
PC
Tsai
Yi-Hung
YH
Huang
Yaw-Bin
YB
D000622:Aminolevulinic Acid / Q000737:chemistry*; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007477:Ions; D008081:Liposomes / Q000737:chemistry*; D008954:Models, Biological; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D012449:Safety; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013228:Stearates / Q000737:chemistry
D004337:Drug Carriers; D007477:Ions; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D013228:Stearates; C483858:phosphatidylethanolamine; D000622:Aminolevulinic Acid; D002784:Cholesterol