Retained topical delivery of 5-aminolevulinic acid using cationic ultradeformable liposomes for photodynamic therapy

• Published in: European journal of pharmaceutical sciences 2011-09, Vol.44 (1), p.149-157
• Main Authors: Oh, Eun kyung, Jin, Su-Eon, Kim, Jin-Ki, Park, Jeong-Sook, Park, Youmie, Kim, Chong-Kook
• Format: Article
• Language: English
• Subjects: 5-Aminolevulinic acid; Administration, Topical; Aminolevulinic Acid - administration & dosage; Aminolevulinic Acid - pharmacokinetics; Aminolevulinic Acid - therapeutic use; Animals; Biological and medical sciences; Cations; Drug Compounding; Drug Stability; General pharmacology; In Vitro Techniques; Liposomes; Male; Medical sciences; Mice; Mice, Hairless; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - pharmacokinetics; Photosensitizing Agents - therapeutic use; Protoporphyrins - biosynthesis; Skin - metabolism; Skin Absorption; Skin Diseases - drug therapy; Skin Diseases - metabolism; Surface Properties; Topical delivery; Ultradeformable liposome
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2011.07.003

5-Aminolevulinic acid (5-ALA), inducing photodynamic protoporphyrin (PpIX), is a hydrophilic molecule, resulting in leashing the capacity to cross tissue barriers like stratum corneum (SC) of skin. Here, we aimed to develop 5-ALA loaded ultradeformable liposomes (UDL) with different surface charges, and to investigate their physicochemical characteristics and capability for the skin penetration and retention of 5-ALA for topical photodynamic therapy (PDT). The effects of surface charges of UDL on in vitro permeation of 5-ALA and in vivo accumulation of 5-ALA−induced PpIX in viable skin were determined and then compared with conventional neutral liposomes (nLiposome). All UDL showed smaller particle size and better deformability than nLiposome. However, entrapment efficiency of 5-ALA was similar to each vesicle. Among vesicles, the cationic UDL (cUDL) demonstrated higher stability and permeability, and could deliver 5-ALA into deep skin tissue by topical application. Moreover, the 5-ALA loaded in cUDL was long retained, and induced more amount of PpIX in viable skin than those in other UDL and nLiposome. Considering that the conversion of 5-ALA into PpIX occurs preferentially in epidermis, these results suggested that topical delivery of 5-ALA loaded in cUDL could be an interesting proposal to optimize PDT related to 5-ALA.