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Lipid cubic phases for improved topical drug delivery in photodynamic therapy.

Journal article
Authors Johanna Bender
Marica B Ericson
Nadia Merclin
V. Iani
Arne Rosen
Sven Engström
J. Moan
Published in Journal of Controlled Release
Volume 106
Issue 3
Pages 350-360
ISSN http://dx.doi.org/10.1016/j.jconrel.2005.05.010
Publication year 2005
Published at Department of Physics (GU)
Pages 350-360
Language en
Links dx.doi.org/10.1016/j.jconrel.2005.0...
Keywords Aminolevulinic acid, Methyl aminolevulinate, Lipid cubic phase, Monoolein, Phytantriol
Subject categories Pharmaceutics

Abstract

We have evaluated the efficacy of lipid cubic phases, highly ordered self-assembly systems on the nanometer level, as drug delivery vehicles for in vivo topical administration of delta-aminolevulinic acid (ALA) and its methyl ester (m-ALA) on nude mice skin. ALA, a precursor of heme, induces the production of the photosensitizer protoporphyrin IX (PpIX) in living tissue. Measuring the PpIX fluorescence at the skin surface, after topical administration, makes indirect quantification of the penetration of ALA into the tissue possible. Cubic phases were formed of lipid (monoolein or phytantriol), water and drug. In some cases, propylene glycol was included in the cubic phase as well. The drug concentration was 3% (w/w, based on the total sample weight) in all investigated vehicles. When the formulations were applied for 1 h, the monoolein cubic systems and the three-component phytantriol sample showed higher fluorescence compared to the standard ointment during the 10 h of measurement. Both ALA and m-ALA yielded similar results, although the differences between the investigated vehicles were more pronounced when using m-ALA. For the 24-h applications, the monoolein cubic systems with m-ALA showed faster PpIX formation than the standard ointment, implying higher PpIX levels at short application times (less than 4 h). The systemic PpIX fluorescence of ALA was elevated by using the lipid cubic formulations. Notably, a small systemic effect was also observed for the monoolein cubic sample with m-ALA. These results imply improved PpIX formation when using the lipid cubic systems, most probably due to enhanced drug penetration.

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