Topical glycerol monooleate/propylene glycol formulations enhance 5-aminolevulinic acid in vitro skin delivery and in vivo protophorphyrin IX accumulation in hairless mouse skin.
Photodynamic therapy (PDT), a potential therapy for cancer treatment, utilizes exogenously applied or endogenously formed photosensitizers, further activated by light in an appropriate wavelength and dose to induce cell death through free radical formation. 5-Aminolevulinic acid (5-ALA) is a pro-drug which can be converted to the effective photosensitizer, protoporphyrin IX (PpIX). However, the use of 5-ALA in PDT is limited by the low penetration capacity of this highly hydrophilic molecule into appropriate skin layers. In the present study, we propose to increase 5-ALA penetration by using formulations containing glycerol monooleate (GMO), an interesting and useful component of pharmaceutical formulations. Propylene glycol solutions containing different concentrations of GMO significantly increased the in vitro skin permeation/retention of 5-ALA in comparison to control solutions. In vivo studies also showed increased PpIX accumulation in mouse hairless skin, after the use of topical 5-ALA formulations containing GMO in a concentration-dependent manner. The results show that skin 5-ALA penetration and PpIX accumulation, important factors for the success of topical 5-ALA-PDT in skin cancer, are optimized by GMO/propylene glycol formulations.
Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Regilene
R
Steluti
Fernanda Scarmato
FS
De Rosa
John
J
Collett
Antônio Cláudio
AC
Tedesco
Maria Vitória Lopes Badra
MV
Bentley
D000279:Administration, Cutaneous; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D002626:Chemistry, Pharmaceutical; D005989:Glycerides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D019946:Propylene Glycol / Q000737:chemistry*; D011524:Protoporphyrins / Q000096:biosynthesis*; D051381:Rats; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*
D005989:Glycerides; D011524:Protoporphyrins; D019946:Propylene Glycol; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; C005953:monoolein