Liposomes with tretinoin:: a physical and chemical evaluation

The comedolytic activity of tretinoin, incorporated in liposomes. is five to ten times higher compared to the conventional preparations and also the local tolerability is much better. This implies the big interest of a study on tretinoin in liposomes. First, the encapsulation capacity of tretinoin in the liposomes was determined. Therefore, a series of liposomes was prepared with different concentrations of tretinoin (1-6 mg/ml buffer) and lipids (100-300 mg/ml buffer) (egg phosphatidyl choline/cholesterol) with buffers pH = 5 and 7. These series of liposomes were evaluated microscopically on the presence of tretinoin crystals outside the liposomes. The highest incorporation capacity was obtained using 2 mg of tretinoin and 300 mg of lipids per milliliter of buffer pH = 5. The chemical stability of tretinoin in the liposomes, evaluated during I year, revealed no remarkable loss in tretinoin content, even when stored at 25 degreesC. The photo-degradation of tretinoin in the liposomes was about two times slower than in castor oil, but tretinoin degraded to approximate to 25% of its initial content. The chemical evaluation of the lipid fraction showed no oxidative degradation of the polyunsaturated fatty acids in EPC because the determined concentration of conjugated dienes and hydroperoxides, two oxidative degradation products, was < 1%, which is negligible. Finally, the in-vitro release of tretinoin from the liposomes, evaluated with a dialysis technique, was very low, but this is not a problem for topical use. (C) 2001 Published by Elsevier Science B.V.