THE CONTROLLED INTRAVENOUS DELIVERY OF DRUGS USING PEG-COATED STERICALLY STABILIZED NANOSPHERES

Injectable blood persistent particulate carriers have important therap eutic application in site-specific drug delivery or medical imaging. H owever, injected particles are generally eliminated by the reticulo-en dothelial system within minutes after administration and accumulate in the liver and spleen. To obtain a coating that might prevent opsoniza tion and subsequent recognition by the macrophages, sterically stabili zed nanospheres were developed using amphiphilic diblock or multiblock copolymers. The nanospheres are composed of a hydrophilic polyethylen e glycol coating and a biodegradable core in which various drugs were encapsulated. Hydrophobic drugs, such as Lidocaine, were entrapped up to 45 wt% and the release kinetics were governed by the polymer physic o-chemical characteristics. Plasma protein adsorption was drastically reduced on PEG-coated particles compared to non-coated ones. Relative protein amounts were time-dependent. The nanospheres exhibited increas ed blood circulation times and reduced liver accumulation, depending o n the coating polyethylene glycol molecular weight and surface density . They could be freeze-dried and redispersed in aqueous solutions and possess good shelf stability. It may be possible to tailor ''optimal'' polymers for given therapeutic applications.