Hexyl aminolaevulinate is a more effective topical photosensitiser precursor than methyl aminolaevulinate and 5-aminolaevulinic acids when applied in equimolar doses.
Aminolaevulinic acid (ALA) is known to poorly penetrate into thick lesions, such as nodular basal cell carcinomas. Short chain ALA esters, possessing increased lipophilicity relative to their hydrophilic parent, have previously been shown to be highly efficient at inducing protoporphyrin IX (PpIX) production in cell culture, at equimolar concentrations. In contrast, in vitro skin permeation and in vivo animal studies, which up to now have compared prodrugs on a % w/w basis, have failed to demonstrate such benefits. For the first time, equimolar concentrations of ALA, methyl-ALA (m-ALA) and hexyl-ALA (h-ALA) have been incorporated into an o/w cream preparation. In vitro penetration studies into excised porcine skin revealed that increased levels of h-ALA, compared to ALA and m-ALA were found in the upper skin layers, at all drug loadings studied. Topical application of the formulations to nude murine skin in vivo, revealed that creams containing h-ALA induced significantly higher levels of peak PpIX fluorescence (F(max) = 289.0) at low concentrations compared to m-ALA (F(max) = 159.2) and ALA (F(max) = 191.9). Importantly, this study indicates that when compared on an equimolar basis, h-ALA has improved skin penetration, leading to enhanced PpIX production compared to the parent drug and m-ALA.
Morrow
Desmond I J
DI
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, UK.
McCarron
Paul A
PA
Woolfson
A David
AD
Juzenas
Petras
P
Juzeniene
Asta
A
Iani
Vladimir
V
Moan
Johan
J
Donnelly
Ryan F
RF
D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D009824:Ointments; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D012867:Skin / Q000737:chemistry / Q000187:drug effects; D012869:Skin Absorption; D013552:Swine
D009824:Ointments; D017319:Photosensitizing Agents; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester