Thursday, May 26, 2016

PLGA-PEG-NH2 from PolySciTech used as part of development of a carrier for crossing the blood-brain-barrier.

PolySciTech division of Akina, Inc ( provides, amongst other products, a wide variety of endcap reactive block copolymers including PLGA-PEG-NH2. One of the challenges for drug delivery is that the human immune and clearance systems do not discriminate between medicine and poison. Any compound introduced into the body is treated by the body in a similar manner in that it is typically up-taken by the liver for metabolic destruction, or screened out by the kidneys to remove into the urine. This is a valuable survival mechanism in the situation of accidental poisoning, but creates challenges for medicinal delivery as a substantial portion of administered medicine is cleared by these and other pathways before it has a chance to act where it is needed. The brain, in particular, is understandably very discriminatory about what is allowed to cross over from the blood stream into the brain tissue. This phenomenon is referred to as the blood-brain-barrier and prevents medicinal delivery to brain tissues. Recently, researchers have utilized PLGA-PEG-NH2 from PolySciTech (PolyVivo AI-058) to generate SiRNA loaded PLGA-PEG nanoparticles decorated with a transferrin receptor to allow for delivery across the blood-brain-barrier. This research holds promise to provide for treatment of a wide variety of neural diseases. Read more: Gomes, Maria João, Carlos Fernandes, Susana Martins, Fernanda Borges, and Bruno Sarmento. "Tailoring Lipid and Polymeric Nanoparticles as siRNA Carriers towards the Blood-Brain Barrier–from Targeting to Safe Administration." Journal of Neuroimmune Pharmacology (2016): 1-13.

“Abstract: Blood-brain barrier is a tightly packed layer of endothelial cells surrounding the brain that acts as the main obstacle for drugs enter the central nervous system (CNS), due to its unique features, as tight junctions and drug efflux systems. Therefore, since the incidence of CNS disorders is increasing worldwide, medical therapeutics need to be improved. Consequently, aiming to surpass blood-brain barrier and overcome CNS disabilities, silencing P-glycoprotein as a drug efflux transporter at brain endothelial cells through siRNA is considered a promising approach. For siRNA enzymatic protection and efficient delivery to its target, two different nanoparticles platforms, solid lipid (SLN) and poly-lactic-co-glycolic (PLGA) nanoparticles were used in this study. Polymeric PLGA nanoparticles were around 115 nm in size and had 50 % of siRNA association efficiency, while SLN presented 150 nm and association efficiency close to 52 %. Their surface was functionalized with a peptide-binding transferrin receptor, in a site-oriented manner confirmed by NMR, and their targeting ability against human brain endothelial cells was successfully demonstrated by fluorescence microscopy and flow cytometry. The interaction of modified nanoparticles with brain endothelial cells increased 3-fold compared to non-modified lipid nanoparticles, and 4-fold compared to non-modified PLGA nanoparticles, respectively. These nanosystems, which were also demonstrated to be safe for human brain endothelial cells, without significant cytotoxicity, bring a new hopeful breath to the future of brain diseases therapies. Keywords: Blood-brain barrier Functionalization Nanoparticles siRNA Targeting TfR-peptide”
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