title: Retained topical delivery of 5-aminolevulinic acid using cationic ultradeformable liposomes for photodynamic therapy.
abstract: 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.
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Oh
authors.forename: Su-Eon
authors.initials: SE
authors.lastname: Jin
authors.forename: Jin-Ki
authors.initials: JK
authors.lastname: Kim
authors.forename: Jeong-Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Youmie
authors.initials: Y
authors.lastname: Park
authors.forename: Chong-Kook
authors.initials: CK
authors.lastname: Kim
mesh_terms: D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D002412:Cations; D004339:Drug Compounding; D004355:Drug Stability; D066298:In Vitro Techniques; D008081:Liposomes; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011524:Protoporphyrins / Q000096:biosynthesis; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012871:Skin Diseases / Q000188:drug therapy / Q000378:metabolism; D013499:Surface Properties
chemical_list: D002412:Cations; D008081:Liposomes; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX