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.[1]References
- Direct cerebrospinal fluid delivery of an antiretroviral agent using multivesicular liposomes. Kim, S., Scheerer, S., Geyer, M.A., Howell, S.B. J. Infect. Dis. (1990) [Pubmed]
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