Pharmaceutical Research

, Volume 18, Issue 10, pp 1411–1419

Biodistribution of Long-Circulating PEG-Grafted Nanocapsules in Mice: Effects of PEG Chain Length and Density

  • Vanessa Carla Furtado Mosqueira
  • Philippe Legrand
  • Jean-Louis Morgat
  • Michel Vert
  • Evgueni Mysiakine
  • Ruxandra Gref
  • Jean-Philippe Devissaguet
  • Gillian Barratt
Article

DOI: 10.1023/A:1012248721523

Cite this article as:
Mosqueira, V.C.F., Legrand, P., Morgat, JL. et al. Pharm Res (2001) 18: 1411. doi:10.1023/A:1012248721523

Abstract

Purpose: To study the pharmacokinetics and biodistribution of novel polyethyleneglycol (PEG) surface-modified poly(rac-lactide) (PLA) nanocapsules (NCs) and to investigate the influence of PEG chain length and content.

Methods: The biodistribution and plasma clearance in mice of different NC formulations were studied with [3H]-PLA. PLA-PEG copolymers were used in NC preparations at different chain lengths (5 kDa and 20 kDa) and PEG contents (10% and 30% w/w of total polymer). In vitro and in vivo stability were also checked.

Results: Limited [3H]-PLA degradation was observed after incubation in mouse plasma for 1 h, probably because of to the large surface area and thin polymer wall. After injection into mice, NCs prepared with PLA-PEG copolymers showed an altered distribution compared to poloxamer-coated PLA NCs. An increased concentration in plasma was also observed for PLA-PEG NCs, even after 24 h. A dramatic difference in the pharmacokinetic parameters of PLA-PEG 45-20 30% NCs compared to poloxamer-coated NCs indicates that covalent attachment, longer PEG chain lengths, and higher densities are necessary to produce an increased half-life of NCs in vivo.

Conclusions: Covalently attached PEG on the surface of NCs substantially can reduce their clearance from the blood compartment and alter their biodistribution.

nanocapsulespoly(rac-lactide)-poly(ethylene glycol) copolymersplasma stabilitybiodistributionplasma clearancePEG chain length

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Vanessa Carla Furtado Mosqueira
    • 1
    • 2
  • Philippe Legrand
    • 1
  • Jean-Louis Morgat
    • 3
  • Michel Vert
    • 3
  • Evgueni Mysiakine
    • 1
  • Ruxandra Gref
    • 1
  • Jean-Philippe Devissaguet
    • 1
  • Gillian Barratt
    • 1
  1. 1.UMR CNRS 8612, Faculté de PharmacieUniversité de Paris-SudChâtenay Malabry CedexFrance
  2. 2.Departamento de Farmácia - Escola de FarmáciaUniversidade Federal de Ouro PretoPreto-Brazil
  3. 3.CRBA, UMR CNRS 5473, Faculté de PharmacieUniversité de Montpellier IMontpellierFrance