title: 5'-O-Palmitoyl- and 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine--novel lipophilic analogues of 5'-fluoro-2'-deoxyuridine: synthesis, incorporation into liposomes and preliminary biological results.
abstract: 5'-O-palmitoyl- and 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine were prepared by the reaction of 5-fluoro-2'-deoxyuridine in dimethylacetamide with palmitic acid chloride. The incorporation of the synthesized prodrugs into liposomes composed of egg phosphatidylcholine/stearylamine/cholesterol/alpha-tocopherol at a molar ratio of 10:1:2:0.05 was nearly quantitative; homogeneous bilayer vesicles (75 nm diameter) were obtained. Preliminary tolerance studies revealed that the prodrug-liposome preparations are about 20-60 times more toxic than the parent drug. The prodrugs incorporated into liposomes were 10 to 30 times more active against murine colon 38 carcinoma compared to the free drug. In comparison to the administration of the prodrugs in peanut oil the liposomal preparations seem to exert improved effects and represent a valuable drug delivery system for parenteral applications.
authors.forename: R A
authors.initials: RA
authors.lastname: Schwendener
authors.forename: A
authors.initials: A
authors.lastname: Supersaxo
authors.forename: W
authors.initials: W
authors.lastname: Rubas
authors.forename: H G
authors.initials: HG
authors.lastname: Weder
authors.forename: H R
authors.initials: HR
authors.lastname: Hartmann
authors.forename: H
authors.initials: H
authors.lastname: Schott
authors.forename: A
authors.initials: A
authors.lastname: Ziegler
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D055598:Chemical Phenomena; D002621:Chemistry; D003110:Colonic Neoplasms / Q000188:drug therapy; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008081:Liposomes / Q000008:administration & dosage*; D051379:Mice; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D005467:Floxuridine; C044351:3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine; C044352:5'-O-palmitoyl-5-fluoro-2'-deoxyuridine