title: Iontophoretic delivery of 5-aminolevulinic acid and its methyl ester using a carbopol gel as vehicle.
abstract: The aim of this study was to evaluate a Carbopol gel as a vehicle for iontophoretic delivery of 5-aminolevulinic acid (ALA) and its methyl ester (m-ALA). The formulation was characterized rheologically and the passive diffusion of ALA and m-ALA in the gels was measured. Addition of ALA and m-ALA did not change the rheological behavior of the gel and the diffusion coefficients of ALA and m-ALA were 4.4 +/- 1.2 x 10(-6) and 3.08 +/- 0.7 x 10(-7) cm2 s(-1), respectively. The anodal iontophoretic transport of ALA and m-ALA through porcine skin in vitro was followed for 15 h at a constant current of 0.4 mA. When incorporating ALA in the gel, the steady-state was reached in 10-12 h at a flux level of approx. 65 nmol cm(-2) h(-1) compared to 2.5-4 h and a level of approximately 145 nmol cm(-2) h(-1) for m-ALA. The total amount of m-ALA delivered after 15 h of iontophoresis resulted in a six-fold enhancement over ALA delivery. Iontophoretic delivery from the gel formulation seems to be better than, or comparable to, the passive delivery from formulations commonly used clinically, in spite of the 10-20 times lower concentration of the drug in the gel formulation. The skin uptake after iontophoresis for m-ALA showed a nine-fold increase over that of ALA in the stratum corneum (SC).
authors.affiliation: Department of Pharmacy, Uppsala Biomedical Centre, Uppsala University, P.O. Box 580, SE-751 23, Sweden. tobias.bramer@farmaci.uu.se
authors.forename: Nadia
authors.initials: N
authors.lastname: Merclin
authors.forename: Tobias
authors.initials: T
authors.lastname: Bramer
authors.forename: Katarina
authors.initials: K
authors.lastname: Edsman
mesh_terms: D000180:Acrylic Resins; D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D005782:Gels; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000295:instrumentation / Q000379:methods*; D011145:Polyvinyls / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013552:Swine
chemical_list: D000180:Acrylic Resins; D005782:Gels; D011145:Polyvinyls; C114767:delta-aminolevulinic acid methyl ester; C006912:carboxypolymethylene; D000622:Aminolevulinic Acid