Transdermal delivery from a lipid sponge phase--iontophoretic and passive transport in vitro of 5-aminolevulinic acid and its methyl ester.
The hydrochloride salts of 5-aminolevulinic acid (ALA) and its methyl ester (m-ALA), respectively, were dissolved in a lipid sponge phase comprising monoolein, propylene glycol and aqueous buffer at concentrations of approximately 0.25% and 16% w/w m-ALA. The iontophoretic and passive delivery of ALA and m-ALA from this formulation through porcine skin in vitro were measured and compared to formulations used in clinical practice, 20% w/w ALA in Unguentum M and Metvix (a cream containing 16% w/w m-ALA). A sponge phase with 16% w/w m-ALA showed a higher passive flux (approximately 140 nmol cm(-2) h(-1) at 5 h) but a lower iontophoretic flux (approximately 800 nmol cm(-2) h(-1) at 5 h) compared to the clinically used products but the differences are hardly significant due to large standard deviations. ALA and m-ALA in sponge phase formulation showed iontophoretic fluxes in the range 80-100 nmol cm(-2) h(-1) at 3 h, i.e. values comparable to the passive fluxes from the more concentrated vehicles. The results demonstrate that the lipid sponge phase, a thermodynamically stable liquid with amphiphilic character, may have potential as a transdermal drug delivery vehicle.
Merclin
N
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Department of Pharmacy, Uppsala Biomedical Centre, Uppsala University, Uppsala, Sweden.
Bender
J
J
Sparr
E
E
Guy
R H
RH
Ehrsson
H
H
Engström
S
S
D000279:Administration, Cutaneous; D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport; D002021:Buffers; D015194:Diffusion Chambers, Culture; D004431:Ear, External / Q000737:chemistry / Q000378:metabolism; D005079:Excipients; D066298:In Vitro Techniques; D007478:Iontophoresis; D008081:Liposomes; D012867:Skin / Q000378:metabolism; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D013552:Swine
D002021:Buffers; D005079:Excipients; D008081:Liposomes; D012996:Solutions; C114767:delta-aminolevulinic acid methyl ester; D000622:Aminolevulinic Acid