TY - JOUR
T1 - The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres
AU - Gref, R.
AU - Domb, A.
AU - Quellec, P.
AU - Blunk, T.
AU - Müller, R. H.
AU - Verbavatz, J. M.
AU - Langer, R.
PY - 1995/9
Y1 - 1995/9
N2 - 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 reticulo-endothelial 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.
AB - 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 reticulo-endothelial 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.
KW - Biodegradable polymers
KW - Hydrophilic coating
KW - Intravenous drug administration
KW - Long-circulating nanoparticles
KW - Polyethylene glycol
KW - Reduced liver accumulation
UR - http://www.scopus.com/inward/record.url?scp=0029360414&partnerID=8YFLogxK
U2 - 10.1016/0169-409X(95)00026-4
DO - 10.1016/0169-409X(95)00026-4
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AN - SCOPUS:0029360414
SN - 0169-409X
VL - 16
SP - 215
EP - 233
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
IS - 2-3
ER -