Topical delivery of 5-aminolevulinic acid-encapsulated ethosomes in a hyperproliferative skin animal model using the CLSM technique to evaluate the penetration behavior.
Psoriasis, an inflammatory skin disease, exhibits recurring itching, soreness, and cracked and bleeding skin. Currently, the topical delivery of 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) is an optional treatment for psoriasis which provides long-term therapeutic effects, is non-toxic and enjoys better compliance with patients. However, the precursor of ALA is hydrophilic, and thus its ability to penetrate the skin is limited. Also, little research has provided a platform to investigate the penetration behavior in disordered skin. We employed a highly potent ethosomal carrier (phosphatidylethanolamine; PE) to investigate the penetration behavior of ALA and the recovery of skin in a hyperproliferative murine model. We found that the application of ethosomes produced a significant increase in cumulative amounts of 5-26-fold in normal and hyperproliferative murine skin samples when compared to an ALA aqueous solution; and the ALA aqueous solution appeared less precise in terms of the penetration mode in hyperproliferative murine skin. After the ethosomes had been applied, the protoporphyrin IX (PpIX) intensity increased about 3.64-fold compared with that of the ALA aqueous solution, and the penetration depth reached 30-80 microm. The results demonstrated that the ethosomal carrier significantly improved the delivery of ALA and the formation of PpIX in both normal and hyperproliferative murine skin samples, and the expression level of tumor necrosis factor (TNF)-alpha was reduced after the ALA-ethosomes were applied to treat hyperproliferative murine skin. Furthermore, the results of present study encourage more investigations on the mechanism of the interaction with ethosomes and hyperproliferative murine skin.
Fang
Yi-Ping
YP
School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
Huang
Yaw-Bin
YB
Wu
Pao-Chu
PC
Tsai
Yi-Hung
YH
D000279:Administration, Cutaneous; D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D008081:Liposomes; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D018613:Microscopy, Confocal / Q000379:methods; D010539:Permeability; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D011524:Protoporphyrins / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy* / Q000503:physiopathology; D012869:Skin Absorption; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; C483858:phosphatidylethanolamine; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX