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PEG-conjugated triacontanol micelles as docetaxel delivery systems for enhanced anti-cancer efficacy

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Abstract

PEGylated triacontanol (mPEG2k-b-TRIA) was developed as a dual-functional polymer with remarkable biocompatibility. The polymer could self-assemble to micelles with critical micelle concentration (CMC) 17.62 μg mL−1. Docetaxel-loaded mPEG2k-b-TRIA micelles (DTX PMs) were fabricated to evaluate the feasibility of mPEG2k-b-TRIA as drug delivery system. DTX PMs achieved desirable particle size of 93.7 nm, drug loading of 6.66%, and drug encapsulation efficiency of 89.87%. The drug release was based on first-order kinetics model, thus enabling prolonged release. Meanwhile, pharmacokinetic study also revealed that DTX PMs could improve the exposure level of DTX and prolong its systemic circulation time. Furthermore, DTX PMs demonstrated significantly enhanced cytotoxicity and cellular uptake in vitro compared with DTX solution. The in vivo tumor inhibition study carried out on MCF-7 bearing BALB/c mice model also validated that DTX PMs exhibited stronger anti-tumor activity but low toxicity. Notably, mPEG2k-b-TRIA made some contribution to inhibit the growth of breast cancer cells in vitro and in vivo, indicating the potential as anti-tumor complementary agents. All the results suggested that mPEG2k-b-TRIA polymer as a vehicle in the formulation of anti-cancer drugs may provide an effective way to improve their therapeutic efficacy. Consequently, the mPEG2k-b-TRIA polymers would be another promising carrier for hydrophobic anti-cancer drugs delivery.

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Abbreviations

AUC:

Area under the curve

CL:

Clearance rate

CLSM:

Confocal laser scanning microscopy

CMC:

Critical micelle concentration

CMPI:

2-Chloro-1-methylpyridinium iodide

DAPI:

4,6-Diamidino-2-phenylindole

DL:

Drug loading

DMAP:

4-Dimethylaminopyridine

DMF:

N,N-Dimethylformamide

DTX:

Docetaxel

DTX-PMs:

Docetaxel-loaded polymeric micelles

EE:

Encapsulation efficiency

EPR:

Enhanced permeability and retention

FT-IR:

Fourier transform infrared

GPC:

Gel permeation chromatography

HBSS:

Hank’s balanced salt solution

1H NMR:

1H nuclear magnetic resonance

IC50 :

Half maximal inhibitory concentration

IR:

Inhibition rate

MRT:

Mean residence time

mPEG2k-NH2 :

Monomethoxy poly(ethylene glycol)-amine; methoxy poly(ethylene glycol 2000)-triacontanol (mPEG2k-b-TRIA)

PBS:

Phosphate-buffered saline

PDI:

Polydispersity index

PEG:

Polyethylene glycol

PMs:

Polymeric micelles

PS:

Physiological saline

SA:

Succinic anhydride

t 1/2 :

Elimination half-life

TEM:

Transmission electron microscope

TRIA:

Triacontanol

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81473272, No. 81503148).

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Authors and Affiliations

  1. Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, 211198, Jiangsu, China

    Xiaoyu Lu, Min Fang, Yue Yang, Yu Dai, Jiaqiu Xu, Di Zhao, Yang Lu & Xijing Chen

  2. College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430000, Hubei, China

    Shan Lu

  3. National Experimental Teaching Demonstration Center of Pharmacy, China Pharmaceutical University, Nanjing, 211198, Jiangsu, China

    Ning Li

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  1. Xiaoyu Lu
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Correspondence to Shan Lu or Ning Li.

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Supplementary Fig. 1

Fitting curve of in vitro release data from DTX PMs for first-order kinetics model (PNG 50 kb)

High-resolution image (TIF 7888 kb)

Supplementary Table 1

(DOCX 25 kb)

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Lu, X., Fang, M., Yang, Y. et al. PEG-conjugated triacontanol micelles as docetaxel delivery systems for enhanced anti-cancer efficacy. Drug Deliv. and Transl. Res. 10, 122–135 (2020). https://doi.org/10.1007/s13346-019-00667-6

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