Effect of the molecular weight of water-soluble polymers on accumulation at an inflammatory site following intravenous injection

Abstract

The body distribution of noncharged, water-soluble polymers, e.g. poly(vinyl alcohol) (PVA), poly(ethylene glycol) (PEG), and dextran, was studied following their intravenous injection into mice with or without carrageenan-induced inflammatory lesions at the femoral muscle. Inflammation induction did not affect their distribution profile, although polymers of high molecular weight tended to remain in the blood circulation for a longer period than those of low molecular weight. Polymers exhibited longer accumulation at the inflammatory site than at the normal site, regardless of the polymer type and the molecular weight estimated by size exclusion chromatography. Maximum accumulation was observed for the polymer having a molecular weight around 200,000, regardless of the polymer type. Pharmacokinetic studies demonstrated that the accumulation rate of polymers at the inflammatory site was higher than at the normal site and decreased with increasing molecular weight. On the other hand, the higher the molecular weight of polymers, the longer the retention time in the blood circulation. Such trends were observed for all types of polymers used, indicating that the inflammatory site accumulation of polymers injected intravenously is governed solely by the polymer molecular weight. The balance between the accumulation rate of polymers and the blood retention seemed to determine the maximum accumulation of polymers having a certain range of molecular weight.