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PEGylated-Paclitaxel and Dihydroartemisinin Nanoparticles for Simultaneously Delivering Paclitaxel and Dihydroartemisinin to Colorectal Cancer

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Abstract

Purpose

Development of a nanoplatform constructed by the PEG-dual drug conjugation for co-delivery of paclitaxel (PTX) and Dihydroartemisinin (DHA) to the tumor.

Methods

PEG was conjugated with PTX and DHA to form PTX-PEG-DHA complex as a nanocarrier. The PTX and DHA were co-encapsulated in PTX-PEG-DHA nanoparticles (PD@PPD NPs) by the emulsion evaporation method. The physicochemical properties of PD@PPD Nps were characterized, including size, zeta potential, and morphology. The drug loading capacity and entrapment efficiency, in vitro drug release at different pH conditions were also evaluated. For in vitro assessment, the effects of the NPs on HT-29 colorectal cancer cells, including intracellular uptake, cytotoxicity, and Bcl-2 protein expression were assessed. The in vivo distribution of the NPs was investigated by labelling the NPs with Cyanine 5.5 fluorophore. Finally, the antitumor efficacy of the NPs was evaluated in HT-29 tumor-bearing mice.

Results

The nanoparticles were formed at small size (~114 nm) and narrow distribution. The combination of PTX and DHA in the DHA-PEG-PTX nanosystems (PD@PPD) showed remarkably increased apoptosis in colorectal adenocarcinoma HT-29 cells, as compared to free drug treatment. More importantly, the PD@PPD nanoparticles exhibited significantly higher accumulation in the tumor site owing to the enhanced permeability and retention (EPR) effect, effectively restrained the tumor growth in vivo at low-dose of PTX while reducing the systemic toxicity.

Conclusions

The combination of PTX and DHA in a PEG-conjugated dual-drug co-delivery system can minimize the severe side effect associated with the high-dose of PTX while enhancing the antitumor efficacy.

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Abbreviations

PTX:

Paclitaxel

DHA:

Dihydroartemisinin

PEG:

Polyethylene glycol

NPs:

Nanoparticles

RES:

Reticuloendothelial system

DLS:

Dynamic Light Scattering

PDI:

Polydispersity Index

EPR:

Enhanced permeability and Retention

TEM:

Transmission electron microscopy

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Funding

This research is funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grant number 108.05–2017.300.

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Author notes

  1. Cao Dai Phung and Thien Giap Le contributed equally to this work.

Authors and Affiliations

  1. College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan, 712-749, South Korea

    Cao Dai Phung, Jong Oh Kim & Chul Soon Yong

  2. National Institute of Pharmaceutical Technology, Hanoi University of Pharmacy, 15 Le Thanh Tong, Hanoi, Vietnam

    Thien Giap Le, Thi Trang Vu, Huong Quynh Nguyen & Chien Ngoc Nguyen

  3. Department of Pharmaceutical Industry, Hanoi University of Pharmacy, 15 Le Thanh Tong, Hanoi, Vietnam

    Van Hai Nguyen & Chien Ngoc Nguyen

Authors
  1. Cao Dai Phung
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Correspondence to Chul Soon Yong or Chien Ngoc Nguyen.

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Phung, C.D., Le, T.G., Nguyen, V.H. et al. PEGylated-Paclitaxel and Dihydroartemisinin Nanoparticles for Simultaneously Delivering Paclitaxel and Dihydroartemisinin to Colorectal Cancer. Pharm Res 37, 129 (2020). https://doi.org/10.1007/s11095-020-02819-7

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  • DOI: https://doi.org/10.1007/s11095-020-02819-7

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