[Study on brain targeting 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine pharmacosomes].
OBJECTIVE
To investigate the specific brain drug targeting of 5-fluoro-2'-deoxyuridine (FUdR) by synthesis of 3', 5'-dioctanoyl-5-fluoro-2'-deoxyuridine (DO-FUdR) and incorporation into DO-FUdR pharmacosomes (DO-FUdR-PS).


METHODS
DO-FUdR-PS was prepared by thin-layer ultrasonication technique. In vitro drug release was studied in pH 7.4 phosphate-buffered saline containing 0.3% pancreatic enzyme at 37 degrees C using bulk-equilirium reverse dialysis bag technique. The concentration of FUdR in various organs were determined by reversed phase HPLC after i.v. administration of DO-FUdR-PS and FUdR.


RESULTS
The mean particle size of DO-FUdR-PS was 76 nm with drug loading of 29.02% and entrapment efficiency of 96.62%. The in vitro drug release kinetics could be characterized by bioexponential equation. Compared with FUdR injection, DO-FUdR-PS showed high concentration in tested organs. The brain AUC ratio of DO-FUdR-PS to FUdR was 10.97.


CONCLUSIONS
DO-FUdR-PS showed a good targeting efficiency in vivo. PS can improve the ability of drug to cross blood-brain barrier and is a promising drug targeting system for the treatment of central nervous system disorders.
Zhang
Z R
ZR
West China School of Pharmacy, Sichuan University, Chengdu 610041, China. zrzzl@mail.sc.cninfo.net
Wang
J X
JX
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D016503:Drug Delivery Systems; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; C051858:3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine