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 a="" affected="" and="" be="" bone-marrow="" both="" by="" can="" chemotherapeutics.="" effect.="" effectiveness="" for="" from="" have="" href="http://www.polyscitech.com/" huazhong="" improved="" inhibitors="" into="" its="" jiao="" kinase="" maximum="" nanoparticles="" of="" other="" peg-plga="" polyscitech="" preferentially="" purchased="" recently="" regions="" requires="" researchers="" science="" shanghai="" technology="" the="" these="" tissue="" to="" tong="" traditional="" treatment="" treatments="" university="" uptake="" using="">www.polyscitech.com50>
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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”
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