Biodistribution of long-circulating PEG-grafted nanocapsules in mice: Effects of PEG chain length and density

被引:243
作者
Mosqueira, VCF
Legrand, P
Morgat, JL
Vert, M
Mysiakine, E
Gref, R
Devissaguet, JP
Barratt, G
机构
[1] Univ Paris Sud, Fac Pharm, CNRS, UMR 8612, F-92296 Chatenay Malabry, France
[2] Univ Montpellier 1, Fac Pharm, CNRS, UMR 5473,CRBA, F-34060 Montpellier, France
[3] Univ Fed Ouro Preto, Escola Farm, Dept Farm, BR-35400000 Ouro Preto, Minas Gerais, Brazil
关键词
nanocapsules; poly(rac-lactide)-poly(ethylene glycol) copolymers; plasma stability; biodistribution; plasma clearance; PEG chain length;
D O I
10.1023/A:1012248721523
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 [H-3]-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 [H-3]-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.
引用
收藏
页码:1411 / 1419
页数:9
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