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Authors Wu X, Wang L, Qiu Y, Zhang B, Hu Z, Jin R
Received 20 July 2017
Accepted for publication 26 September 2017
Published 31 October 2017 Volume 2017:12 Pages 8025—8034
DOI https://doi.org/10.2147/IJN.S146875
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Govarthanan Muthusamy
Peer reviewer comments 3
Editor who approved publication: Dr Linlin Sun
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
* 在 8025 页,第一个隶属单位应该是:
“Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China”
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