In vivo study of an instantly formed lipid-water cubic phase formulation for efficient topical delivery of aminolevulinic acid and methyl-aminolevulinate
Artikel i vetenskaplig tidskrift, 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

Methylaminolevulinate

Instantly formed cubic phase

Topical delivery

Glyceryl monooleyl ether

Författare

Hanne Evenbratt

Chalmers, Kemi- och bioteknik, Farmaceutisk teknologi

Charlotte A Jonsson

Göteborgs universitet

Jan Faergemann

Sahlgrenska universitetssjukhuset

Sven Engström

Chalmers, Kemi- och bioteknik, Farmaceutisk teknologi

Marica B Ericson

Göteborgs universitet

International Journal of Pharmaceutics

0378-5173 (ISSN)

Vol. 452 270-275

Ämneskategorier

Dermatologi och venereologi

Annan kemi

DOI

10.1016/j.ijpharm.2013.05.047