Thursday, January 23, 2014

PLGA-PEG-Maleimide for crossing the blood brain barrier (BBB)

Did you know that PolySciTech also provides several thiol-reactive PLGA/PLA-PEG-Maleimides (AI20, AI40, AI47, AI48, AI49, AI50, AI52, AI53)? These polymers allow for the conjugation of peptides, antibodies, or other ligands so that the surface of the resultant nanoparticle can interface with cell-receptors. These same types of polymers have previously been used to aid the uptake of tempol across the blood-brain-barrier (BBB).  Read more at: Carroll, Richard T., Deepak Bhatia, Werner Geldenhuys, Ruchi Bhatia, Nicholas Miladore, Anupam Bishayee, and Vijaykumar Sutariya. "Brain-targeted delivery of Tempol-loaded nanoparticles for neurological disorders." Journal of Drug Targeting 18, no. 9 (2010): 665-674. http://informahealthcare.com/doi/abs/10.3109/10611861003639796


“Abstract: Brain-targeted Tempol-loaded poly-(lactide-co-glycolide) (PLGA) nanoparticles (NPs) conjugated with a transferrin antibody (OX 26) were developed using the nanoprecipitation method. These NPs may have utility in treating neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Central to these diseases is an increased production of reactive oxygen and nitrogen species which may take part in the development of these conditions. As proof of principle, the NPs were loaded with Tempol, a free radical scavenger that has been shown to be protective against oxidative insults. To enhance the delivery of NPs to the central nervous system (CNS), we conjugated the transferrin receptor antibody covalently to PLGA NPs using the NHS-PEG3500-Maleimide crosslinker. The NPs showed a particle size suitable for blood brain barrier (BBB) permeation (particle size 80–110 nm) and demonstrated a sustained drug release behavior. A high cellular uptake of antibody-conjugated NPs was demonstrated in RG2 rat glioma cells. The ability of the Tempol-loaded NPs to prevent cell death by resveratrol in RG2 cells was determined using the MTT assay. The conjugated NPs containing Tempol were more effective in preventing cell viability by resveratrol when compared with unconjugated NPs or free Tempol in solution. Our findings suggest that transferrin-conjugated NPs containing antioxidants may be useful in the treatment of neurodegenerative diseases.”
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