title: Enhanced brain targeting by synthesis of 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine and incorporation into solid lipid nanoparticles.
abstract: To overcome the limited access of the drug 5-fluoro-2'-deoxyuridine (FUdR) to the brain, 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine (DO-FUdR) was synthesized and incorporated into solid lipid nanoparticles (DO-FUdR-SLN). DO-FUdR-SLN were prepared by a thin-layer ultrasonication technique and a central composite design (CCD) was applied to optimize the formulation. The median particle size of DO-FUdR-SLN was 76 nm with drug loading of 29.02% and entrapment efficiency of 96.62%. The in vitro drug release was studied by a bulk-equilibrium reverse dialysis bag technique in phosphate-buffered saline (pH 7.4) containing 0.3% pancreatic enzyme at 37 degrees C. The concentrations of FUdR in various organs were determined by reversed-phase high-performance liquid chromatography after intravenous administration of DO-FUdR-SLN, DO-FUdR or FUdR. The brain area under the concentration-time curve of DO-FUdR-SLN and DO-FUdR were 10.97- and 5.32-fold higher than that of FUdR, respectively. These results indicated that DO-FUdR-SLN had a good brain targeting efficiency in vivo. SLN can improve the ability of the drug to penetrate through the blood-brain barrier and is a promising drug targeting system for the treatment of central nervous system disorders.
authors.affiliation: Shanghai Institute of Chinese Materia Medica, Shanghai, People's Republic of China.
authors.forename: Jian Xin
authors.initials: JX
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D008081:Liposomes; D008297:Male; D051379:Mice; D036103:Nanotechnology / Q000379:methods*
chemical_list: D008081:Liposomes; D005467:Floxuridine; C051858:3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine