Wednesday, November 14, 2018

PLGA from PolySciTech used in developing DP44mt loaded nanoparticles for cancer therapy against resistant cancers


DP44mt is a chelator molecule that binds iron and removes it from the intracellular environment. In cancer cells, this agent acts to induce cancer-cell death through upregulation of AMPK pathway and through corrupting autophagic mechanisms. One of the benefits of this therapeutic molecule is that it works against strains of cancers which are resistant to conventional chemotherapy. Recently, researchers at University of Houston purchase PLGA (AP041) from PolySciTech (www.polyscitech.com) for use in developing nanoparticles loaded with DP44mt. This research holds promise to provide for improved therapies against chemoresistant tumors. Read more: Holley, C. K., S. Alkhalifah, and S. Majd. "Fabrication and Optimization of Dp44mT-Loaded Nanoparticles." In 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), pp. 5733-5736. IEEE, 2018. https://ieeexplore.ieee.org/abstract/document/8513598/

“This paper describes the modulation of polymeric nanoparticle (NP) preparation to produce an optimal nanocarrier for delivery of the potent anti-tumor iron chelator, Di2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) towards application in cancer therapy. We have previously shown the potential of poly (lactic-co-glycolic acid) (PLGA) NPs as a nano-carrier for delivery of Dp44mT to malignant cells. The focus of this study is to alter the fabrication parameters to improve the characteristics of these NPs as a delivery vehicle for Dp44mT. To this end, PLGA NPs encapsulating Dp44mT are fabricated using the nanoprecipitation method with systematic variations in (i) the amount of surfactant poly (vinyl alcohol) (PVA) in aqueous phase, and (ii) the drug to polymer ratio in organic phase. The resultant NPs are characterized for size, surface potential, encapsulation efficiency, and drug release profile. Results of this study showed that increasing the PVA % (within the examined range of 0.5-4% w/v) and decreasing the Dp44mT to PLGA ratio (within the tested range of 0.0375-0.3: 1 mg/mL) both led to an increase in drug encapsulation efficiency. Focusing on the optimal PVA percentage, we found that the changes in drug to polymer ratio did not have a significant impact on the size distribution and surface potential of Dp44mT-NPs and these NPs remained in the desirable range of 80-120 nm. Lastly, the release of Dp44mT from NPs differed for different Dp44mT: PLGA ratios, providing a means to further optimize the NP formulation for future cancer treatment applications. Keywords: Drugs, Encapsulation, Polymers, Cancer, Fabrication, Nanoparticles, Iron”

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