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

  • Xiaoyu Lu
  • Min Fang
  • Yue Yang
  • Yu Dai
  • Jiaqiu Xu
  • Di Zhao
  • Yang Lu
  • Xijing Chen
  • Shan LuEmail author
  • Ning LiEmail author
Original Article

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.

Keywords

Micelles Docetaxel Biocompatible polymers Drug delivery Triacontanol 

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

t1/2

Elimination half-life

TEM

Transmission electron microscope

TRIA

Triacontanol

Notes

Funding

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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Animal studies

All institutional and national guidelines for the care and use of laboratory animals were followed.

Supplementary material

13346_2019_667_Fig10_ESM.png (50 kb)
Supplementary Fig. 1

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

13346_2019_667_MOESM1_ESM.tif (7.7 mb)
High-resolution image (TIF 7888 kb)
13346_2019_667_MOESM2_ESM.docx (25 kb)
Supplementary Table 1 (DOCX 25 kb)

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Copyright information

© Controlled Release Society 2019

Authors and Affiliations

  • Xiaoyu Lu
    • 1
  • Min Fang
    • 1
  • Yue Yang
    • 1
  • Yu Dai
    • 1
  • Jiaqiu Xu
    • 1
  • Di Zhao
    • 1
  • Yang Lu
    • 1
  • Xijing Chen
    • 1
  • Shan Lu
    • 2
    Email author
  • Ning Li
    • 3
    Email author
  1. 1.Clinical Pharmacokinetics LaboratoryChina Pharmaceutical UniversityNanjingChina
  2. 2.College of PharmacyHubei University of Chinese MedicineWuhanChina
  3. 3.National Experimental Teaching Demonstration Center of PharmacyChina Pharmaceutical UniversityNanjingChina

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