Pharmacokinetics of a Novel HIV-1 Protease Inhibitor Incorporated into Biodegradable or Enteric Nanoparticles following Intravenous and Oral Administration to Mice

CGP 57813 is a peptidomimetic inhibitor of human immunodeficiency virus type 1 (HIV-1) protease. This lipophilic compound was successfully entrapped into poly(D,L-lactic acid) (PLA) and pH sensitive methacrylic acid copolymers nanoparticles. The intravenous administration to mice of PLA nanoparticle...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 1995-12, Vol.84 (12), p.1387-1391
Main Authors: Leroux, Jean-Christophe, Cozens, Robert, L.Roesel, Johannes, Galli, Bruno, Kubel, Frank, Doelker, Eric, Gurny, Robert
Format: Article
Language:English
Subjects:
Acrylic Resins - chemistry
Administration, Oral
AIDS/HIV
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Biological and medical sciences
Biological Availability
Carbamates - administration & dosage
Carbamates - pharmacokinetics
Delayed-Action Preparations
Drug Carriers
Drug Delivery Systems
Half-Life
HIV Protease Inhibitors - administration & dosage
HIV Protease Inhibitors - pharmacokinetics
Injections, Intravenous
Lactates
Lactic Acid
Medical sciences
Mice
Mice, Inbred BALB C
Oligopeptides - administration & dosage
Oligopeptides - pharmacokinetics
Pharmacology. Drug treatments
Polyesters
Polymers
Polymethacrylic Acids - chemistry
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Summary:CGP 57813 is a peptidomimetic inhibitor of human immunodeficiency virus type 1 (HIV-1) protease. This lipophilic compound was successfully entrapped into poly(D,L-lactic acid) (PLA) and pH sensitive methacrylic acid copolymers nanoparticles. The intravenous administration to mice of PLA nanoparticles loaded with CGP 57813 resulted in a 2-fold increase of the area under the plasma concentration-time curve, compared to a control solution. An increase in the elimination half-life (from 13 to 61 min) and in the apparent volume of distribution (1.7-3.6 L/kg) was observed for the nanoparticle incorporated compound vs control solution. Following oral administration, only nanoparticles made of the methacrylic acid copolymer soluble at low pH provided sufficient plasma levels of CGP 57813. In vitro, these nanoparticles dissolved completely within 5 min at pH 5.8. PLA nanoparticles, which are insoluble in the gastrointestinal tract, did not provide significant plasma concentrations of CGP 57813. From these observations, one can conclude that the passage of intact PLA nanoparticles across the gastrointestinal mucosa appears to be very low.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.2600841202