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A Promising Emodin-Loaded Poly (Lactic-Co-Glycolic Acid)-d-α-Tocopheryl Polyethylene Glycol 1000 Succinate Nanoparticles for Liver Cancer Therapy

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ABSTRACT

Purpose

Emodin (EMO) has multi-targets and multi-way antitumor effect, which was limited by the instability and poor solubility of EMO. The aim of this study was to formulate EMO-loaded poly (lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (EPTN) to increase the liver targeting of EMO for cancer therapy.

Methods

EMO/coumarin-6-loaded PLGA-TPGS nanoparticles (ECPTN) and EMO-loaded PLGA nanoparticles (EPN) were also prepared as comparison. The cellular uptake of ECPTN by HepG2 and HCa-F cells was investigated using Confocal laser scanning microscopy. The apoptosis of HepG2 cells handled with EPTN was assayed by flow cytometry. The liver targeting property of ECPTN in mice was evaluated using the drug concentration determined by RP-HPLC and the freezing slices were investigated via fluorescence inversion microscopy. The blood samples were obtained from vein intubation to illustrate the pharmacokinetics process of EPTN. The tumor-bearing mice model was established to elucidate the in vivo therapeutic effect of EPTN.

Results

The results demonstrated that ECPTN could be internalized by HepG2 and HCa-F cells respectively. The ratio of apoptosis cells was increased after dealing with EPTN. The detection indexes of drug concentration and fluorescence inversion microscopy images indicated ECPTN had an excellent effect on liver targeting property than EMO solutions (EMS). The pharmacokinetics process of EPTN showed obvious sustained-release effect than EMS. Compared with EPN, the in vivo antitumor activity of EPTN against tumor cells were better.

Conclusions

In conclusion, EPTN could be used in the treatment of liver cancer acted as a kind of promising intravenous dosage forms.

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Abbreviations

AUC:

Area under concentration-time curve

C6:

Coumarin-6

DL:

Drug-loading

ECPTN:

EMO/coumarin-6-loaded PLGA-TPGS nanoparticles

EE:

Encapsulation efficiency

EMO:

Emodin

Empty PTN:

Empty PLGA-TPGS nanoparticles

EMS:

EMO solutions

EPN:

EMO-loaded PLGA nanoparticles

EPTN:

EMO-loaded PLGA-TPGS nanoparticles

FS:

5-Fluorouracil solutions

PDI:

Polydispersity index

PLGA:

Polylactic-co-glycolic acid

PLGA-TPGS:

Poly (lactic-co-glycolic acid)-d-α-tocopheryl polyethylene glycol 1000 succinate

Re:

Relative targeting efficiency

SI:

Selectivity index

Te:

Targeting efficiency

TI:

Targeting index

TPGS:

D-α-tocopheryl polyethylene glycol 1000 succinate

ZP:

Zeta potential

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors are grateful for material support from Dr Lin Mei who works at Tsinghua University. The authors alone are responsible for the content and writing of this article. The authors ensure that this article content has no any conflict of interest.

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Authors and Affiliations

  1. College of Pharmacy, Dalian Medical University, Dalian, 116044, China

    Hongyan Liu, Meng Gao, Xin Guan, Li Lv, Sa Deng & Yan Tian

  2. College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China

    Hong Xu & Chenghong Zhang

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  1. Hongyan Liu
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  2. Meng Gao
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  3. Hong Xu
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  4. Xin Guan
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  7. Chenghong Zhang
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  8. Yan Tian
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Correspondence to Yan Tian.

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Liu, H., Gao, M., Xu, H. et al. A Promising Emodin-Loaded Poly (Lactic-Co-Glycolic Acid)-d-α-Tocopheryl Polyethylene Glycol 1000 Succinate Nanoparticles for Liver Cancer Therapy. Pharm Res 33, 217–236 (2016). https://doi.org/10.1007/s11095-015-1781-4

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