Enhancement of topical delivery of a lipophilic drug from charged multilamellar liposomes

To enhance the topical delivery of rhodamine B base (Rho), a model lipophil ic compound, the electrostatic interaction between the positive and negativ e components incorporated in the liposomal bilayer was utilized. The higher in vitro permeability to Rho in rat skin was observed with positive and ne utral multilamellar liposomal preparations, the former was prepared with ph osphatidylcholine (PC) and stearylamine (SA) and the latter with PC alone, than that given as a solution. Negative liposome composed of PC and dicetyl phosphate (DCP) showed lower skin permeability to Rho. To enhance the Rho retention in the skin, the electrostatic interaction between SA and DCP, wh ich was confirmed by in vitro partition study, was utilized. By pretreating the skin surface with SA solution or empty SA liposome, the skin distribut ion of Rho given as DCP liposome was substantially enhanced, with increase in the PC distribution into the skin. The pretreatment effect of empty SA l iposome was also observed in rats in vivo. In conclusion, it was found that negative DCP liposome provides better drug retention in the skin with lowe r skin permeability, and the topical drug delivery from DCP liposome was fu rther enhanced by the pretreatment of the skin surface with empty SA liposo me.