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

Purpose. To study the pharmacokinetics and biodistribution of novel polyeth yleneglycol (PEG) surface-modified poly(rac-lactide) (PLA) nanocapsules (NC s) and to investigate the influence of PEG chain length and content. Methods. The biodistribution and plasma clearance in mice of different NC f ormulations 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 content s (10% and 30% w/w of total polymer). In vitro and in vivo stability were a lso checked. Results. Limited [H-3]-PLA degradation was observed after incubation in mou se plasma for 1 h, probably because of to the large surface area and thin p olymer wall. After injection into mice, NCs prepared with PLA-PEG copolymer s showed an altered distribution compared to poloxamer-coated PLA NCs. An i ncreased concentration in plasma was also observed for PLA-PEG NCs, even af ter 24 h. A dramatic difference in the pharmacokinetic parameters of PLA-PE G 45-20 30% NCs compared to poloxamer-coated NCs indicates that covalent at tachment, longer PEG chain lengths, and higher densities are necessary to p roduce an increased half-life of NCs in vivo. Conclusions. Covalently attached PEG on the surface of NCs substantially ca n reduce their clearance from the blood compartment and alter their biodist ribution.