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Idarubicin-loaded methoxy poly(ethylene glycol)-b-poly(L-lactide-co-glycolide) nanoparticles for enhancing cellular uptake and promoting antileukemia activity

Authors Liang B, Li N, Zhang S, Qi A, Feng J, Jing W, Shi C, Ma Z, Gao S

Received 7 October 2018

Accepted for publication 10 December 2018

Published 11 January 2019 Volume 2019:14 Pages 543—556

DOI https://doi.org/10.2147/IJN.S190027

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 2

Editor who approved publication: Dr Mian Wang


Bin Liang,1,* Na Li,2,* Shuofei Zhang,3 Aihua Qi,4 Jianhua Feng,1 Weiwei Jing,5 Changcan Shi,2 Zhaipu Ma,6 Shenmeng Gao7

1Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou, Zhejiang 325000, China; 2Wenzhou Institute of Biomaterials and Engineering, CNITECH, CAS, Wenzhou, Zhejiang 325000, China; 3Department of Orthodontics, Stomatological Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; 4Department of Internal Medicine, Zaoqiang People’s Hospital, Zaoqiang, Hebei 053100, China; 5Department of Obstetrics and Gynecology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, Zhejiang 325000, China; 6Department of Bioinformatics, College of Life Science, Hebei University, Baoding, Hebei 071002, China; 7Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou, Zhejiang 325000, China

*These authors contributed equally to this work

Purpose: Nanoparticle (NP)-based drug delivery approaches have tremendous potential for enhancing treatment efficacy and decreasing doses of chemotherapeutics. Idarubicin (IDA) is one of the most common chemotherapeutic drugs used in the treatment of acute myeloid leukemia (AML). However, severe side effects and drug resistance markedly limit the application of IDA.
Methods: In this study, we encapsulated IDA in polymeric NPs and validated their antileukemia activity in vitro and in vivo.
Results: NPs with an average diameter of 84 nm was assembled from a methoxy poly(ethylene glycol)-b-poly(l-lactide-co-glycolide) (mPEG-PLGA). After loading of IDA, IDA-loaded mPEG-PLGA NPs (IDA/mPEG-PLGA NPs) were formed. The in vitro release data showed that the IDA/mPEG-PLGA NPs have excellent sustained release property. IDA/mPEG-PLGA NPs had exhibited the lower IC50 than pure IDA. Moreover, IDA/mPEG-PLGA NPs in the same concentration substantially induced apoptosis than did pure IDA. Most importantly, IDA/MPEG-PLGA NPs significantly decreased the infiltration of leukemia blasts and improved the overall survival of MLL-AF9-induced murine leukemia compared with free IDA. However, the blank NPs were nontoxic to normal cultured cells in vitro, suggesting that NPs were the safe carrier.
Conclusion: Our data suggest that IDA/mPEG-PLGA NPs might be a suitable carrier to encapsulate IDA. Low dose of IDA/mPEG-PLGA NPs can be used as a conventional dosage for antileukemia therapy to reduce side effect and improve survival.

Keywords: idarubicin, mPEG-PLGA, acute myeloid leukemia, nanoparticles

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