Soluble polymeric carriers for drug delivery. Part 2. Preparation and in vivo behaviour of N-acylethylenimine copolymers

Abstract

The preparation, characterization and in vivo behaviour of novel N-acylethylenimine (NAEI) copolymers are described and the potential use of such materials for drug-delivery applications is discussed. 2-Methyl-2-oxazoline (MeOZO) and 2-(4-hydroxyphenyl)-2-oxazoline (HOPheOZO) were copolymerised in bulk, in vacuo to give water-soluble copolymers of weight average molecular weights ( M w ) of below 30,000 Da. M w was determined by GPC using poly(oxyethylene) (POE) as calibrant. Poly[ N-(2-hydroxypropyl)methacrylamide] [poly(HPMA)] was also examined by GPC and the results were compared with those from the NAEI copolymers. Narrow molecular weight fractions of the copolymers were radioiodinated to give two 125I-labelled copolymers of M w = 15,300 Da , and M w = 29,300 Da , with polydispersity M w M n ⩽ 1.3 , in both cases. These were administered intravenously to mice and an assessment was made of their biodistribution. 24 h after administration of the 15,300 Da ( M w ) 125I-labelled copolymer, 7% of the injected dose was found in whole blood. This compares with 28% of the injected dose remaining after 24 h, following administration of the 29,300 Da ( M w ) 125I-labelled copolymer. The overall biodistribution pattern of both iodinated copolymers was found to be very similar. A significant amount of the copolymers appeared to remain in the body after leaving the vascular compartment, with a tendency to accumulate in the skin and muscle. No accumulation of radioactivity was found associated with organs of the mononuclear phagocyte system.