title: Synthesis and biological evaluation of two glycerolipidic prodrugs of didanosine for direct lymphatic delivery against HIV.
abstract: Novel glycerolipidic prodrugs of didanosine and didanosine monophosphate designed to by-pass the hepatic first pass metabolism were synthesized and tested for their cytotoxicity and anti-HIV-1 activity. Formulation as liposomes of dipalmitoylphosphatidylcholine was elaborated. A simple quantitative HPLC-UV method was developed and validated, and ESI-MS was used for qualitative purpose. These two prodrugs exhibited promising biological activities against HIV-1 in in vitro infected cell culture.
authors.affiliation: Université Paris-Sud, UMR CNRS 8612, IFR 141, F-92296 Châtenay-Malabry, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Lalanne
authors.forename: Angelo
authors.initials: A
authors.lastname: Paci
authors.forename: Karine
authors.initials: K
authors.lastname: Andrieux
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.forename: Pascal
authors.initials: P
authors.lastname: Clayette
authors.forename: Alain
authors.initials: A
authors.lastname: Deroussent
authors.forename: Micheline
authors.initials: M
authors.lastname: Ré
authors.forename: Gilles
authors.initials: G
authors.lastname: Vassal
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.forename: Didier
authors.initials: D
authors.lastname: Desmaële
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002478:Cells, Cultured; D016049:Didanosine / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008081:Liposomes; D008208:Lymphatic System / Q000378:metabolism* / Q000821:virology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011684:Purine Nucleosides / Q000008:administration & dosage / Q000627:therapeutic use; D014280:Triglycerides / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D008081:Liposomes; D011355:Prodrugs; D011684:Purine Nucleosides; D014280:Triglycerides; D016049:Didanosine