Synthesis and biological evaluation of two glycerolipidic prodrugs of didanosine for direct lymphatic delivery against HIV.
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.
Lalanne
Muriel
M
Université Paris-Sud, UMR CNRS 8612, IFR 141, F-92296 Châtenay-Malabry, France.
Paci
Angelo
A
Andrieux
Karine
K
Dereuddre-Bosquet
Nathalie
N
Clayette
Pascal
P
Deroussent
Alain
A
Ré
Micheline
M
Vassal
Gilles
G
Couvreur
Patrick
P
Desmaële
Didier
D
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
D019380:Anti-HIV Agents; D008081:Liposomes; D011355:Prodrugs; D011684:Purine Nucleosides; D014280:Triglycerides; D016049:Didanosine