Enhancement of topical delivery of a lipophilic drug from charged multilamellar liposomes.
To enhance the topical delivery of rhodamine B base (Rho), a model lipophilic compound, the electrostatic interaction between the positive and negative components incorporated in the liposomal bilayer was utilized. The higher in vitro permeability to Rho in rat skin was observed with positive and neutral multilamellar liposomal preparations, the former was prepared with phosphatidylcholine (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, which was confirmed by in vitro partition study, was utilized. By pretreating the skin surface with SA solution or empty SA liposome, the skin distribution of Rho given as DCP liposome was substantially enhanced, with increase in the PC distribution into the skin. The pretreatment effect of empty SA liposome was also observed in rats in vivo. In conclusion, it was found that negative DCP liposome provides better drug retention in the skin with lower skin permeability, and the topical drug delivery from DCP liposome was further enhanced by the pretreatment of the skin surface with empty SA liposome.
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
N
N
Katahira
T
T
Murakami
S
S
Kugai
N
N
Yata
M
M
Takano
D000287:Administration, Topical; D000588:Amines / Q000737:chemistry; D000818:Animals; D004337:Drug Carriers; D004563:Electrochemistry; D066298:In Vitro Techniques; D008081:Liposomes; D008297:Male; D010755:Organophosphates / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012869:Skin Absorption / Q000187:drug effects*
D000588:Amines; D004337:Drug Carriers; D008081:Liposomes; D010755:Organophosphates; D010713:Phosphatidylcholines; D012235:Rhodamines; C002290:dicetylphosphate; C009317:stearylamine; C029773:rhodamine B