The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres

• Main Authors: Gref, R (Author), Domb, A (Author), Quellec, P (Author), Blunk, T (Author), Müller, RH (Author), Verbavatz, JM (Author), Langer, R (Author)
• Format: Article
• Language: English
• Published: Elsevier BV, 2021-10-27T20:05:07Z.
• Subjects: Article
• Online Access: Get fulltext

 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. © 2012.