Pharmacokinetics and pharmacodynamics of sterylglucoside-modified liposomes for levonorgestrel delivery via nasal route.
For emergency contraceptive, the rapid delivery of levonorgestrel (LNG) to plasma is desirable, furthermore, a sustained delivery of LNG along with rapid absorption will be necessary. The pharmacokinetics and pharmacodynamics of LNG entrapped in different kinds of liposome formulations via nasal administration in rats were evaluated and compared with LNG suspension via the oral route. The relative bioavailabilities of these liposome formulations via nasal administration were 100% or higher than 100%. The Cmax and Tmax values of sterylglucoside (SG) and chitosan-contained formulations by nasal administration were 416.84 ng/mL and 1.02 hr, 227.97 ng/mL and 2.02 hr, respectively, compared with that of 334.94 ng/mL and 1.89 hr of oral suspension. Fully 100% contraception was observed for all the formulations. SG could promote the absorption of LNG via the nasal route and may provide a rapid onset of action of LNG for emergency contraception. Chitosan could retain LNG in the nasal cavity for long contact time to sustain delivery of LNG. The rapid onset and sustained delivery of LNG can be achieved via the nasal route using liposomes as the vehicle.
Ding
Wu-Xiao
WX
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Qi
Xian-Rong
XR
Fu
Qiang
Q
Piao
Hui-Shan
HS
D000042:Absorption; D000269:Adhesives; D000281:Administration, Intranasal; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D048271:Chitosan; D003282:Contraceptives, Postcoital, Hormonal / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D008081:Liposomes; D009297:Nasal Mucosa / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000269:Adhesives; D003282:Contraceptives, Postcoital, Hormonal; D008081:Liposomes; D016912:Levonorgestrel; D048271:Chitosan