Jejunal absorption, pharmacological activity, and pharmacokinetic evaluation of indomethacin-loaded poly(d,l-lactide) and poly(isobutyl-cyanoacrylate) nanocapsules in rats.
The jejunal absorption of indomethacin nanocapsules was studied using an in vivo infusion technique. Jejunal absorption of indomethacin from the nanocapsules was slightly delayed as compared to a commercial indomethacin solution. The plasma and jejunal mucosa indomethacin concentrations were similar in both cases. However, the nanocapsules protected the rat jejunum from the ulcerating effect of indomethacin, probably by avoiding direct contact of the free drug with the surface of the mucosa. The pharmacokinetic profile of indomethacin nanocapsule formulations was compared to a solution of free drug following oral administration of 5 mg/kg in rats; no difference in the mean concentration-time profiles of the drug was observed. Blood levels of thromboxane showed a sustained biological activity, over a period of 24 hr, of indomethacin-loaded nanocapsules, relative to the drug in solution, following oral administration.
Ammoury
N
N
Laboratoire de Pharmacie Galénique et Biopharmacie, URA CNRS 1218, Centre d'Etudes Pharmaceutiques, Chatenay-Malabry, France.
Fessi
H
H
Devissaguet
J P
JP
Dubrasquet
M
M
Benita
S
S
D000818:Animals; D002214:Capsules; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003487:Cyanoacrylates / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D004659:Enbucrilate; D066298:In Vitro Techniques; D007213:Indomethacin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism; D008297:Male; D010477:Perfusion; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control; D013929:Thromboxane B2 / Q000097:blood
D002214:Capsules; D003487:Cyanoacrylates; D011091:Polyesters; D011108:Polymers; C033616:poly(lactide); D013929:Thromboxane B2; D004659:Enbucrilate; D007213:Indomethacin