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

• Published in: Pharmaceutical research 2001-10, Vol.18 (10), p.1411-1419
• Main Authors: FURTADO MOSQUEIRA, Vanessa Carla, LEGRAND, Philippe, MORGAT, Jean-Louis, VERT, Michel, MYSIAKINE, Evgueni, GREF, Ruxandra, DEVISSAGUET, Jean-Philippe, BARRATT, Gillian
• Format: Article
• Language: English
• Subjects: Adsorption; Algorithms; Animals; Area Under Curve; Biodistribution; Biological and medical sciences; Capsules; Copolymers; Excipients; General pharmacology; Injections, Intravenous; Lactic Acid; Medical sciences; Mice; Nanoemulsions; Nanotechnology; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacokinetics; Pharmacology. Drug treatments; Plasma; Poloxamer; Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacokinetics; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Structure-Activity Relationship; Surfactants; Tissue Distribution
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/a:1012248721523

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