Direct cerebrospinal fluid delivery of an antiretroviral agent using multivesicular liposomes.
The use of multivesicular liposomes for administration of antiviral agents into cerebrospinal fluid was explored in a Sprague-Dawley rat model. DDC (2',3'-dideoxycytidine) was encapsulated into multivesicular liposomes made from dioleoyl lecithin, dipalmitoyl phosphatidylglycerol, cholesterol, and triolein. The half-lives of drug leakage in human plasma and in 0.9% NaCl were 15 and 47 h, respectively. After intraventricular injection with a stereotaxic apparatus, DDC levels within the central nervous system decreased exponentially, with a half-life of 1.1 h for the unencapsulated DDC and 23 h for the liposome-encapsulated DDC. There were no abnormalities observed in the behavior of the rats. Encapsulation of a more hydrophilic antiviral agent is expected to increase the half-life even further. The results of this study offer the possibility of a practical intrathecal drug delivery for drugs that do not cross the blood-brain barrier.
Kim
S
S
Department of Medicine, University of California, San Diego, La Jolla 92093.
Scheerer
S
S
Geyer
M A
MA
Howell
S B
SB
D000818:Animals; D004337:Drug Carriers; D006207:Half-Life; D007278:Injections, Spinal; D008081:Liposomes; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016047:Zalcitabine / Q000008:administration & dosage* / Q000493:pharmacokinetics
D004337:Drug Carriers; D008081:Liposomes; D016047:Zalcitabine