John Garner

PEG-PLGA from PolySciTech used in development of nanoparticle-based Leukemia treatment

Blog Post created by John Garner on Dec 8, 2017

Xiaoyan, 2017 PMC5673049 PolySciTech nanoparticles PEG-PLGA leukemia.JPG

Leukemia is a cancer which affects how blood cells are produced in bone marrow and contributes to about 24,500 deaths each year in US. T cell acute lymphoblastic leukemia (T-ALL), in particular is a form of leukemia which has poor survival prognosis in adult (<50%) its treatment requires both kinase inhibitors and traditional chemotherapeutics. The effectiveness of these treatments can be improved by using nanoparticles to preferentially have uptake into the bone-marrow tissue and other affected regions for maximum effect. Recently, researchers from Shanghai Jiao Tong University and Huazhong University of Science and Technology Purchased PEG-PLGA from PolySciTech (www.polyscitech.com) to make nanoparticles co-loaded with both IRAK (kinase inhibitor) and ABT-737 (microtubule-targeting chemotherapeutic) for leukemia therapy. This research holds promise to improve therapeutic and survival outcomes for this difficult to treat disease. Read more: Wu, Xiaoyan, Lin Wang, Yining Qiu, Bingyu Zhang, Zhenhua Hu, and Runming Jin. "Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia." International Journal of Nanomedicine 12 (2017): 8025. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673049/

“Abstract: T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology. The optimal parameter comprised 2.98% polymer in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12% emulsifier concentration. High drug loading and uniform spherical shape was achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor for 72 hours as well as sustained release of ABT-737 for more than 120 hours. Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT-NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC50 of IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells. Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution. Keywords: T cell acute lymphoblastic leukemia, IRAK1/4 inhibitor, ABT-737, Box-Behnken design and response surface methodology, PEG-PLGA”

Outcomes