Repeated injection of PEGylated solid lipid nanoparticles induces accelerated blood clearance in mice and beagles.

摘要: Surface modification of nanocarriers with amphiphilic polymer polyethylene glycol (PEG), known as PEGylation, is regarded a major breakthrough in the application nanocarriers. However, PEGylated (including liposomes and polymeric nanoparticles) induce what referred to “accelerated blood clearance (ABC) phenomenon” upon repeated injection consequently they lose their sustained circulation characteristics. Despite this, present authors are not aware any reports accelerated due for solid lipid nanoparticles (SLNs), another promising nanocarrier. This study investigated pharmacokinetics SLNs administration mice; moreover, impact time on induction ABC phenomenon was studied beagles first time. The index, selected ratio area under concentration-time curve from 0 last measured concentration second that injection, used evaluate extent this phenomenon. Results showed exhibited systemic both mice beagles, different intervals, which index significant difference within 30 minutes following good enough magnitude ABC. indicated 10 mol% PEG suitable prolonged induced most marked research. demonstrated that, like such nanoparticles, – beagle valuable experimental animal Furthermore, considered relatively extended initial dose may be underlying factor determining