Targeting of 3'-azido 3'-deoxythymidine (AZT)-loaded poly(isohexylcyanoacrylate) nanospheres to the gastrointestinal mucosa and associated lymphoid tissues.
OBJECTIVE
The aim of the studv was to evaluate the capacity of poly(isohexylcyanoacrylate) nanospheres to concentrate 3'-azido 3'-deoxythymidine (AZT) in the intestinal epithelium and associated immunocompetent cells, which are known to be one of the major reservoirs of the human immunodeficiency virus (HIV).


METHODS
The tissue concentration of 3H-radiolabeled AZT in the gastrointestinal (GI) tract was obtained 30 and 9() minutes after intragastric administration to rats at a dose of 0.25 mg AZT/100 g of body weight. The distribution along the intestine was determined. AZT concentrations in the lymph were obtained by lymphatic duct cannulation.


RESULTS
Unlike the solution. nanoparticles did concentrate AZT very cfficiently in the intestinal mucosa, as well as in the Peyer's patches, and could simultaneously control the release of free AZT. Concentration in Peyer's patches was 4 times higher for nanoparticles, compared with the control solution. The tissue concentration was 30-45 microM, which was much higher than the reported IC50 of AZT (0.06-1.36 microM) and was regularly distributed along the gastrointestinal tract.


CONCLUSIONS
Nanoparticles have been shown to be efficient in concentrating AZT in the intestinal epithelium and gut-associated lymphoid tissues, supporting the view that these particles may represent a promising carrier to treat specifically the GI reservoir of HIV.
Dembri
A
A
UMR 8612, Université de Paris XI, Châtenay-Malabry, France.
Montisci
M J
MJ
Gantier
J C
JC
Chacun
H
H
Ponchel
G
G
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003487:Cyanoacrylates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000187:drug effects / Q000378:metabolism*; D008863:Microspheres; D051381:Rats; D017208:Rats, Wistar; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D003487:Cyanoacrylates; C057532:polyisohexylcyanoacrylate; D015215:Zidovudine