Monday, May 22, 2017

PLGA-PEG-amine from PolySciTech used to generate brain-penetrating nanoparticles for treatment of neural diseases

A significant problem in treating disease which affect the brain is that getting medicine into the brain tissue is very difficult. This is due to the ‘blood-brain-barrier’ which prevents medicines in the bloodstream from crossing over into the brain tissue. This is a unique feature of the brain, as other organs (kidneys, liver, lungs, etc.) readily absorb medicines from the blood stream. A simple method to overcome this barrier is to simply dose the medicine so high that even if a small portion of the drug crosses into the brain it is effective. However, this strategy does not work with medicines that have side-effects at high doses. Another method of dealing with this problem is to generate medicine-loaded nanoparticles which are specifically modified in such a way as to allow them to penetrate across the blood-brain barrier so they can deliver medicine into the brain for treatment of neural diseases. Recently, researchers working jointly at University of Southern Denmark (Denmark) and Instituto de Investigacao e Inovacao em Saude (Portugal) utilized PLGA-PEG-NH2 from PolySciTech (www.polyscitech.com) (PolyVivo AI058) to generate transferrin decorated nanoparticles for blood-brain-barrier penetration. This research holds promise for improved delivery of medicine to brain tissue for improved treatment of cancer or neural disease such as alzeheimers. Read more: Gomes, Maria Joao, Patrick J. Kennedy, Susana Martins, and Bruno Sarmento. "Delivery of siRNA silencing P-gp in peptide-functionalized nanoparticles causes efflux modulation at the blood–brain barrier." Nanomedicine 0 (2017). http://www.futuremedicine.com/doi/abs/10.2217/nnm-2017-0023


“Aim: Explore the use of transferrin-receptor peptide-functionalized nanoparticles (NPs) targeting blood–brain barrier (BBB) as siRNA carriers to silence P-glycoprotein (P-gp). Materials & methods: Permeability experiments were assessed through a developed BBB cell-based model; P-gp mRNA expression was evaluated in vitro; rhodamine 123 permeability was assessed after cell monolayer treatment with siRNA NPs. Results: Beyond their ability to improve siRNA permeability through the BBB by twofold, 96-h post-transfection, functionalized polymeric NPs successfully reduced P-gp mRNA expression up to 52%, compared with nonfunctionalized systems. Subsequently, the permeability of rhodamine 123 through the human BBB model increased up to 27%. Conclusion: Developed BBB-targeted NPs induced P-gp downregulation and consequent increase on P-gp substrate permeability, revealing their ability to modulate drug efflux at the BBB.”
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