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

• Published in: International journal of pharmaceutics Vol. 452; no. 1-2; pp. 270 - 275
• Main Authors: Evenbratt, Hanne, Jonsson, Charlotte, Faergemann, Jan, Engström, Sven, Ericson, Marica B.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 16.08.2013
• Subjects: Administration, Cutaneous; Aminolevulinic acid; Aminolevulinic Acid - administration & dosage; Aminolevulinic Acid - analogs & derivatives; Aminolevulinic Acid - chemistry; Aminolevulinic Acid - pharmacokinetics; Animals; Annan kemi; Dermatologi och venereologi; Dermatology and Venereal Diseases; drugs; emulsions; Fatty Alcohols - chemistry; Female; fluorescence; Glycerides - chemistry; Glyceryl monooleate; Glyceryl monooleyl ether; Glycols - chemistry; hydrochloric acid; in vivo studies; Instantly formed cubic phase; Methylaminolevulinate; Mice; Mice, Hairless; Other Chemistry Topics; Pentanes - chemistry; propylene glycol; Propylene Glycol - chemistry; protoporphyrin; salts; solvents; Topical delivery; Water - chemistry; X-ray diffraction; PDT; Methylaminolevulinate; Topical delivery; Glyceryl monooleyl ether; Glyceryl monooleate; GMO; PpIX; POL; Aminolevulinic acid; ALA; PG; MAL; API; Instantly formed cubic phase; SAXD; GME
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2013.05.047

We demonstrate a rapidly formed cubic liquid crystalline phase, i.e. typically 1g cubic phase in less than 1min 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 δ-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®), 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.