Liposomes for (trans)dermal delivery of tretinoin: influence of drug concentration and vesicle composition

The influence of drug concentration and vesicle composition on the (trans)dermal delivery of tretinoin (TRA) was studied. To this purpose tretinoin was incorporated at different concentrations in unilamellar liposomes (UVs) prepared by sonication using phospholipids with different transition temperature (Tc): hydrogenated soy phosphatidylcholine (Tc = 51°C) or dipalmitoylphosphatidylcholine (Tc = 41°C). Vesicle dispersions were characterized in terms of morphology, size distribution and incorporation efficiency by using respectively optical and polarized light microscopy, transmission electron microscopy, dynamic laser light scattering, and HPLC. The effect of the vesicular incorporation of tretinoin at different molar ratios was investigated by zeta potential measurements and differential scanning calorimetry analysis. These analyses indicated that tretinoin principally interacts with the lipid groups until bilayer saturation. At higher concentration the ionized drug interacts with the polar head. Interactions between new-born pig skin and vesicle containing different amount of tretinoin were evaluated in vitro using Franz cells. The results obtained confirmed that liposomes saturated with TRA (molar fraction = 0.3) are capable of significantly promoting drug accumulation in the pig skin and that (trans)cutaneous delivery is strongly dependent on vesicular stability on the skin.