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

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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.

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Authors and Affiliations

  1. UMR CNRS 8612, Faculté de Pharmacie, Université de Paris-Sud, 5, Rue Jean-Baptiste Clément, Châtenay Malabry Cedex, 92296, France

    Vanessa Carla Furtado Mosqueira, Philippe Legrand, Evgueni Mysiakine, Ruxandra Gref, Jean-Philippe Devissaguet & Gillian Barratt

  2. Departamento de Farmácia - Escola de Farmácia, Universidade Federal de Ouro Preto, Rua Costa Sena, 171-Ouro, Preto-, 35400000, Minas Gerais, Brazil

    Vanessa Carla Furtado Mosqueira

  3. CRBA, UMR CNRS 5473, Faculté de Pharmacie, Université de Montpellier I, 15 Av. Charles-Flahault, Montpellier, 34060, France

    Jean-Louis Morgat & Michel Vert

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  1. Vanessa Carla Furtado Mosqueira
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  2. Philippe Legrand
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  7. Jean-Philippe Devissaguet
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Mosqueira, V.C.F., Legrand, P., Morgat, JL. et al. Biodistribution of Long-Circulating PEG-Grafted Nanocapsules in Mice: Effects of PEG Chain Length and Density. Pharm Res 18, 1411–1419 (2001). https://doi.org/10.1023/A:1012248721523

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