Friday, August 14, 2015

Mal-Peg-PLGA used for generating decorated nanoparticles to cross the blood-brain-barrier

One of the challenges in modern medicine is getting pharmaceutics to cross into the brain. The human brain is extremely selective about what it absorbs out of the blood-stream and many helpful medicines end up trapped on the blood side of the capillaries with no means to cross into the brain tissue itself. The blood-brain-barrier (BBB) is necessary for healthy brain function, but feature this makes treating various brain ailments such as cancer, alzeheimers, and other diseases extremely difficult as only a very small fraction of the medicine administered to the patient actually makes it into the brain tissue where it is needed. For this reason, many researchers have focused on various techniques for assisting medicines in crossing the blood-brain-barrier as a means to treat neurological diseases.  PolySciTech (www.polyscitech.com) provides a wide array of biodegradable block copolymers including Maleimide-PEG-PLGA which is useful for generating nanoparticles capable of crossing the BBB. Recently researchers used phage display and screening techniques to obtain a 12-amino acid peptide (Pep TGN) that allowed for particles to cross the BBB. They conjugated this peptide to the Maleimide-PEG-PLGA to generate a nanoparticle capable of crossing the BBB and confirmed its effectiveness in a mouse model. Read more: Li, Jingwei, Liang Feng, Li Fan, Yuan Zha, Liangran Guo, Qizhi Zhang, Jun Chen et al. "Targeting the brain with PEG–PLGA nanoparticles modified with phage-displayed peptides." Biomaterials 32, no. 21 (2011): 4943-4950. (Full-Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727047/)


“Abstract: The relative impermeability of the blood-brain barrier (BBB) results from tight junctions and efflux transport systems limits drug delivery to the central nervous system (CNS), and thus severely restricts the therapy of many central nervous system diseases. In order to enhance the brain-specific drug delivery, we employed a 12-mer phage display peptide library to isolate peptides that could target the drug delivery system to the brain. A 12-amino-acid-peptide (denoted as Pep TGN) which was displayed by bacteriophage Clone 12-2 was finally selected by rounds of in vivo screening. Pep TGN was covalently conjugated onto the surface of poly (ethyleneglycol)-poly (lactic-co-glycolic acid) (PEG-PLGA) based nanoparticles (NPs). The cellular uptake of Pep TGN decorated nanoparticles was significantly higher than that of unmodified nanoparticles when incubated with bEnd.3 cells. Enhanced brain accumulation efficiency together with lower accumulation in liver and spleen was observed in the nude mice intravenously injected with Pep TGN conjugated nanoparticles compared with those injected with plain nanoparticles, showing powerful brain selectivity of Pep TGN. Coumarin 6 was used as a fluorescent probe for the evaluation of brain delivery properties. The brain Drug Targeting Index (DTI) of coumarin 6 incorporated in targeted nanoparticles was significantly higher than that of coumarin 6 incorporated in plain nanoparticles. In conclusion, the Pep TGN is a motif never been reported before and Pep TGN modified nanoparticles showed great potential in targeted drug delivery across the blood brain barrier. Keywords: Phage display, blood-brain barrier (BBB), brain delivery, biodegradable nanoparticle”
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