Transdermal delivery from a lipid sponge phase—iontophoretic and passive transport in vitro of 5-aminolevulinic acid and its methyl ester

• Published in: Journal of controlled release Vol. 100; no. 2; pp. 191 - 198
• Main Authors: Merclin, N., Bender, J., Sparr, E., Guy, R.H., Ehrsson, H., Engström, S.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 2004; Elsevier
• Subjects: Administration, Cutaneous; Aminolevulinic Acid - administration & dosage; Aminolevulinic Acid - analogs & derivatives; Aminolevulinic Acid - pharmacokinetics; Animals; Biological and medical sciences; Biological Transport; Buffers; Chemical Sciences; delta-Aminolevulinic acid methyl ester; Diffusion Chambers, Culture; Ear, External - chemistry; Ear, External - metabolism; Excipients; Fysikalisk kemi; General pharmacology; In Vitro Techniques; Iontophoresis; Kemi; Liposomes; Medical sciences; Medicin och hälsovetenskap; methyl ester; Monoolein; Natural Sciences; Naturvetenskap; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physical Chemistry; Skin - metabolism; Solutions; Spectrophotometry, Ultraviolet; Sponge phase; Swine; Transdermal delivery; δ-Aminolevulinic acid; Transdermal delivery; Iontophoresis; δ-Aminolevulinic acid; Monoolein; Sponge phase; Pharmaceutical technology; Sponge phase; Monoolein; 6-Aminolevulinic acid; Animal origin; Passive transport; Lipids; In vitro; Percutaneous route; Marine environment; 5-Aminolevulinic acid; Ester; Acids; Porifera; methyl ester; Transdermal delivery; Iontophoresis; Invertebrata
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2004.08.025

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.