Glioblastoma is a form of brain cancer in which malignant glial cells spread to various areas of the brain. This form of cancer is very difficult to treat and requires specific manipulations of the biochemistry of the malignant cells to kill them. Gefitinib acts to dephosphorylate Bcl-2 associated death promoter (BAD) and GSK461364A induces cell cycle arrest at G2/M phase. Both of these mechanisms lead to apoptosis (cell death) and together these drugs can act synergistically to be potent treatment against cancer. Recently, researchers at University of Massachusetts Lowell utilized mPEG-PLGA (AK027) and PLGA (AP023) from PolySciTech (www.polyscitech.com) to create dual-loaded nanoparticles and tested these for use as a treatment against glioblastoma. This research holds promise to provide new therapeutic options against this lethal form of cancer. Read more: Velpurisiva, Praveena, and Prakash Rai. "Synergistic Action of Gefitinib and GSK41364A Simultaneously Loaded in Ratiometrically-Engineered Polymeric Nanoparticles for Glioblastoma Multiforme." Journal of Clinical Medicine 8, no. 3 (2019): 367. https://www.mdpi.com/2077-0383/8/3/367
“Abstract: Glioblastoma Multiforme is a deadly cancer of glial cells with very low survival rates. Current treatment options are invasive and have serious side effects. Single drug treatments make the tumor refractory after a certain period. Combination therapies have shown improvements in treatment responses against aggressive forms of cancer and are becoming a mainstay in the management of cancer. The purpose of this study is to design a combinatorial treatment regimen by engineering desired ratios of two different small molecule drugs (gefitinib and GSK461364A) in a single carrier that can reduce off-target effects and increase their bioavailability. Synergistic effects were observed with our formulation when optimal ratios of gefitinib and GSK461364A were loaded in poly (lactic-co-glycolic) acid and polyethylene glycol (PLGA-PEG) nanoparticles and tested for efficacy in U87-malignant glioma (U87-MG) cells. Combination nanoparticles proved to be more effective compared to single drug encapsulated nanoparticles, free drug combinations, and the mixture of two single loaded nanoparticles, with statistically significant values at certain ratios and drug concentrations. We also observed drastically reduced clonogenic potential of the cells that were treated with free drugs and nanoparticle combinations in a colony forming assay. From our findings, we conclude that the combination of GSK461364A and higher concentrations of gefitinib when encapsulated in nanoparticles yield synergistic killing of glioma cells. This study could form the basis for designing new combination treatments using nanoparticles to deliver multiple drugs to cancer cells for synergistic effects. Keywords: combination therapy; cancer; glioblastoma multiforme; polymeric nanoparticles; gefitinib; GSK461364A; drug resistance; synergistic effect; drug interaction; enhanced permeation and retention”
-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com
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