title: The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres.
abstract: 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.
authors.affiliation: Laboratoire de Chimie-Physique Macromoléculaire, URA CNRS 494, ENSIC, 1, Rue Grandville, BP 451, 54001 Nancy Cedex, France.
authors.forename: R
authors.initials: R
authors.lastname: Gref
authors.affiliation: Department of Pharmaceutical Chemistry, Hebrew University, 91120 Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Domb
authors.affiliation: Laboratoire de Chimie-Physique Macromoléculaire, URA CNRS 494, ENSIC, 1, Rue Grandville, BP 451, 54001 Nancy Cedex, France.
authors.forename: P
authors.initials: P
authors.lastname: Quellec
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Christian-Albrechts-University Kiel, Gutenbergstr, 76-78, 24118 Kiel, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Blunk
authors.affiliation: Department of Pharmaceutics, Biopharmaceutics and Biotechnology, Free University of Berlin, Kelchstr, 31, 12169 Berlin, Germany.
authors.forename: R H
authors.initials: RH
authors.lastname: Müller
authors.affiliation: Service de Biologie Cellulaire, CEA Saclay, 91191 Gif sur Yvette, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Verbavatz
authors.affiliation: Department of Chemical Engineering, MIT, E25-342, 45 Carlton St., Cambridge, MA 02139, USA.
authors.forename: R
authors.initials: R
authors.lastname: Langer
keywords: Biodegradable polymers; Hydrophilic coating; Intravenous drug administration; Long-circulating nanoparticles; Polyethylene glycol; Reduced liver accumulation