Wednesday, October 26, 2016

PLGA-PEG-Mal, and PLGA-Rhodamine from PolySciTech used for development of targeted nanoparticle as part of brain cancer treatment

One critical challenge in medicine is appropriate delivery of drug molecules to the tissue or cells of interest. Recently, researchers at the Canadian Institut National de la Recherche Scientifique (INRS) utilized PLGA-Peg-Mal (PolyVivo Cat# AI052) and PLGA-Rhodamine (PolyVivo Cat# AV011) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to develop a glutathione decorated nanoparticle for improved curcumin delivery to neural cells. This research holds promise for improved chemotherapeutic strategies for brain cancer. Read more: Paka, Ghislain Djiokeng, and Charles Ramassamy. "Optimization of curcumin loaded-PEG-PLGA nanoparticles by GSH functionalization. Investigation of the internalization pathway in neuronal cells." Molecular Pharmaceutics (2016). http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.6b00738

“One major challenge in the field of nanotherapeutics is to increase the selective delivery of cargo to targeted cells. Using Poly Lactic-co-Glycolic Acid (PLGA), we recently highlighted the importance of polymer composition in the biological fate of the nanodrug delivery systems. However the route of internalisation of polymeric nanoparticles (NPs) is another key component to consider in the elaboration of modern and targeted devices. For that purpose, herein, we effectively synthesized and characterised glutathione- functionalized PLGA-nanoparticles (GSH-NPs) loaded with curcumin (GSH-NPs-Cur), using thiol-maleimide click reaction and determined their physicochemical properties. We found that GSH- functionalization did not affect the drug loading efficiency (DLE), the size, the polydispersity index (PDI), the zeta potential, the release profile and the stability of the formulation. While being non-toxic, the presence of GSH on the surface of the formulations exhibits a better neuroprotective property against acrolein. The neuronal internalisation of GSH-NPs-Cur was higher than with free curcumin. In order to track the intracellular localisation of the formulations, we used a covalently attached Rhodamine (PLGA-Rhod), into our GSH-functionalized matrix. We found that GSH-functionalized matrix could easily be taken up by neuronal cells. Furthermore, we found that GSH-conjugation modifies the route of internalisation enabling them to escape the uptake through macropinocytosis and therefore avoiding the lysosomal degradation. Taken together, GSH-functionalization increases the uptake of formulations and modifies the route of internalization towards a safer pathway. This study shows that the choice of ideal ligand to develop NPs-targeting devices is a crucial step when designing innovative strategy for neuronal cells delivery.”
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