The role of PEG on the stability in digestive fluids and in vivo fate of PEG-PLA nanoparticles following oral administration

Injectable nanoparticulate carriers have important potential applications such as site-specific drug delivery or medical imaging. Conventional carriers, however, cannot generally be used because they are eliminated by the reticulo-endothelial system within seconds or minutes after intravenous injection. To address these limitations, monodisperse biodegradable nanospheres were developed from amphiphilic copolymers composed of two biocompatible blocks. The nanospheres exhibited dramatically increased blood circulation times and reduced liver accumulation in mice. Furthermore, they entrapped up to 45 percent by weight of the drug in the dense core in a one-step procedure and could be freeze-dried and easily redispersed without additives in aqueous solutions.

Injectable blood persistent particulate carriers have important therapeutic application in site-specific drug delivery or medical imaging. However, injected particles are generally eliminated by the reticuloendothelial system within minutes after administration and accumulate in the liver and spleen. To obtain a coating that might prevent opsonization and subsequent recognition by the macrophages, sterically stabilized nanospheres were developed using amphiphilic diblock or multiblock copolymers. The nanospheres are composed of a hydrophilic polyethylene 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 physico-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 increased blood circulation times and reduced liver accumulation, depending on 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.

Non-ionic and carboxylated fluorescent polystyrene microspheres (100, 500 nm, 1 and 3 microns in diameter), were fed by gavage (2.5% w/v; 1.25 mg kg-1) daily for 10 days to female Sprague Dawley rats. Peyer's patches, villi, liver, lymph nodes and spleen of animals fed the non-ionic microspheres from 100 nm to 1 micron showed unequivocal evidence of uptake and translocation of the particles. Heart, kidney and lung showed no evidence of the presence of microspheres. Carboxylated microspheres were taken up to a lesser degree than the non-ionised particles. Experiments with 125I radiolabelled 100 nm and 1 micron particles showed a higher uptake of the smaller particles, which were concentrated in GI tissue and liver. Particles were not distributed randomly in the tissues, but were concentrated at the serosal side of the Peyer's patches and could be seen traversing the mesentery lymph vessels towards the lymph nodes. The results demonstrate a need to re-examine the possibilities of particulate oral delivery, as well as the potential toxicity of ingested particulates.