Biodistribution of long-circulating PEG-grafted nanocapsules in mice: effects of PEG chain length and density.
OBJECTIVE
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.
Mosqueira
V C
VC
UMR CNRS 8612, Faculté de Pharmacie, Université de Paris-Sud, Châtenay Malabry, France.
Legrand
P
P
Morgat
J L
JL
Vert
M
M
Mysiakine
E
E
Gref
R
R
Devissaguet
J P
JP
Barratt
G
G
D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D002214:Capsules; D005079:Excipients; D007275:Injections, Intravenous; D019344:Lactic Acid; D051379:Mice; D036103:Nanotechnology; D010316:Particle Size; D020442:Poloxamer; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D002214:Capsules; D005079:Excipients; D011108:Polymers; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols