Friday, May 23, 2014

iNGR-PEG-PLGA nanoparticles for treatment of brain cancer

PolySciTech (www.polyscitech.com) provides a wide array of actiavatable PLGA-PEG copolymers including PLGA-PEG-COOH which can be conjugated to amines by carbodiimide techniques. Recent research has shown that a similar polymer can be conjugated to iNGR peptide and formulated into a paclitaxel nanoparticle which has preferential targeting towards brain tumors. Read more: Kang, Ting, Xiaoling Gao, Quanyin Hu, Di Jiang, Xingye Feng, Xue Zhang, Qingxiang Song et al. "iNGR-modified PEG-PLGA nanoparticles that recognize tumor vasculature and penetrate gliomas." Biomaterials 35, no. 14 (2014): 4319-4332. http://www.sciencedirect.com/science/article/pii/S0142961214001264

“Abstract: A major cross-cutting problem for glioma therapy is the poor extravasation and penetration of the payload drug in target glioma parenchyma. Here, to overcome these obstacles, a tumor vessel recognizing and tumor penetrating system is developed by functionalizating the poly (ethyleneglycol)-poly (l-lactic-co-glycolic acid) nanoparticles with an iNGR moiety (iNGR-NP). The nanoparticulate formulation is expected to achieve specific deep penetration in the tumor tissue by initially binding to aminopeptidase N, with iNGR proteolytically cleaved to CRNGR, and then bind with neuropilin-1 to mediate deep penetration in the tumor parenchyma. iNGR-NP exhibits significantly enhanced cellular uptake in human umbilical vein endothelial cells, improves the anti-proliferation and anti-tube formation abilities of paclitaxel in vitro. Following intravenous administration, iNGR-NP present favorable pharmacokinetic and tumor homing profiles. Glioma distribution and penetration assays confirm that iNGR-NP achieve the highest accumulation and deepest penetration at the glioma sites. The anti-glioma efficacy of paclitaxel-loaded iNGR-NP is verified by its improved anti-angiogenesis activity and the significantly prolonged survival time in mice bearing intracranial glioma. These evidences highlight the potential of iNGR-decorated nanoparticles in overcoming the leading edge problem in anti-glioma drug delivery. Keywords: iNGR peptide; Drug delivery; Nanoparticles; Penetration; Glioma therapy”
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