Combined effect of liposomalization and addition of glycerol on the transdermal delivery of isosorbide 5-nitrate in rat skin.
In this report, we investigated the combined effect of drug liposomalization and addition of glycerol on the transdermal delivery of isosorbide 5-nitrate (ISN) in rat abdominal skin in vitro. Occlusive application of both liposomal and aqueous ISN solution, with and without addition of 5% glycerol, showed that drug liposomalization and addition of glycerol has far-reaching implications for ISN permeation and accumulation in 4 and 8 weeks old rat abdominal skin. Using 8 weeks old rat abdominal skin, the optimal concentration of glycerol to be added to liposomal ISN was found to be 5%. The ISN mean values permeated through and accumulated in stripped 8 weeks old rat abdominal skin from those formulations described above were not significant different, which might indicate the combined effect of glycerol and liposomal ISN resides solely in the stratum corneum (SC). Based on previous reports, the enhancement effect of glycerol might be due to an increase in the SC hydration, and perhaps due to subtle changes in the lipid organization caused by penetration of liposomal lipids within the SC intercellular spaces. These data might provide evidence that glycerol action on SC is useful to facilitate skin permeation and accumulation of drugs formulated in liposome.
Barichello
José Mario
JM
Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan.
Yamakawa
Noriko
N
Kisyuku
Masatoshi
M
Handa
Hiroshi
H
Shibata
Taiki
T
Ishida
Tatsuhiro
T
Kiwada
Hiroshi
H
D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D005990:Glycerol / Q000494:pharmacology*; D066298:In Vitro Techniques; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics
D004337:Drug Carriers; D008081:Liposomes; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate; D005990:Glycerol