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

Abstract

Injectable blood persistent particulate carriers have important therapeutic application in sitespecific 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 timedependent. 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.

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“…PLA NPs exhibited an enhancement of the anti-leishmanial effects of primaquine (Muriel et al 1998). MPEG-PLA diblock copolymer has been used for intravenous drug delivery due to its biodegradability and non-toxic behavior (Gref et al 1995).…”

Multiphase microfluidic synthesis of micro- and nanostructures for pharmaceutical applications

“…Novel carriers hold great promise in achieving enhanced bioavailability, reduced cytotoxicity, targeted delivery, controlled release, and improved efficacy that can ultimately result in desired therapeutic responses in the body. Among these carriers, micro- (Kurmi et al, 2010;Leong and Wang, 2015;Skorb and Möhwald, 2014) and nano- (Gref et al, 2012;Peer et al, 2007;Schroeder et al, 2010;Wang et al, 2012) structures have attracted significant research interest because of their tunability in physical (size, structures, porosity, and mechanical strength) and chemical (compositions, reactivity, biocompatibility, and biodegradability) properties, and flexibility in integrating different functions, such as for active/passive targeting, stimuli-responsive release, and diagnostics/imaging. To enable their full potential in practical pharmaceutical applications, the development of advanced and robust platform technologies for the manufacture of microand nanostructured materials with high degree of uniformity (size, size distribution, and shape), batch-to-batch reproducibility and scale-up possibilities, becomes highly essential.…”