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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

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

Bin Liang, Na Li, Shuofei Zhang, Aihua Qi, Jianhua Feng, Weiwei Jing, Changcan Shi, Zhaipu Ma, Shenmeng Gao

Int J Nanomedicine. 2019 Jan 11;14:543-556.

PMID: 30666113

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS74324	Methoxy poly(ethylene glycol)-b-poly(L-lactide)			Price

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