In vivo study of an instantly formed lipid-water cubic phase formulation for efficient topical delivery of aminolevulinic acid and methyl-aminolevulinate
Journal article, 2013

We demonstrate a rapidly formed cubic liquid crystalline phase, i.e. typically 1 g cubic phase in less than 1 min confirmed by X-ray diffraction, consisting of an ether lipid, 1-glyceryl monooleyl ether (GME), an aprotic solvent (propylene glycol or pentane-1,5-diol) and water. The efficacy of the cubic formulation was tested in vivo by administrating formulations containing 3% (w/w) of the HCl salts of delta-aminolevulinic acid (ALA) or methylaminolevulinate (MAL) to hairless mice. The endogenous formation of protoporphyrin IX (PpIX) was monitored spectrophotometrically as a marker for cellular uptake of active compound. As reference, a commercial product containing 16% (w/w) MAL in an oil-in-water emulsion (Metvix (R)), and a cubic phase based on an ester lipid (glyceryl monooleate, GMO), previously shown to facilitate topical delivery of both ALA and MAL, were applied. It was found that in general the cubic phases gave rise to higher fluorescence levels than the mice exposed to the commercial product. The instantly formed cubic formulations based on GME demonstrated the same efficiency as the GMO based formulations. The results imply that instantly formed cubic formulations opens up new opportunities, particularly for transdermal drug delivery of substances subject to stability problems in, e. g. aqueous environments.

Aminolevulinic acid

Glyceryl monooleate


Instantly formed cubic phase

Topical delivery

Glyceryl monooleyl ether


Hanne Evenbratt

Chalmers, Chemical and Biological Engineering, Pharmaceutical Technology

Charlotte A Jonsson

University of Gothenburg

Jan Faergemann

Sahlgrenska University Hospital

Sven Engström

Chalmers, Chemical and Biological Engineering, Pharmaceutical Technology

Marica B Ericson

University of Gothenburg

International Journal of Pharmaceutics

0378-5173 (ISSN)

Vol. 452 1-2 270-275

Subject Categories

Dermatology and Venereal Diseases

Other Chemistry Topics



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