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Pharmaceutical Research

, 35:13 | Cite as

Optimization of Weight Ratio for DSPE-PEG/TPGS Hybrid Micelles to Improve Drug Retention and Tumor Penetration

  • Ya Jin
  • Zimei Wu
  • Caibin Li
  • Weisai Zhou
  • John P. Shaw
  • Bruce C. Baguley
  • Jianping LiuEmail author
  • Wenli ZhangEmail author
Research Paper
  • 454 Downloads

Abstract

Purpose

To enhance therapeutic efficacy and prevent phlebitis caused by Asulacrine (ASL) precipitation post intravenous injection, ASL-loaded hybrid micelles with size below 40 nm were developed to improve drug retention and tumor penetration.

Methods

ASL-micelles were prepared using different weight ratios of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethyleneglycol-2000 (DSPE-PEG2000) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymers. Stability of micelles was optimized in terms of critical micelle concentration (CMC) and drug release properties. The encapsulation efficiency (EE) and drug loading were determined using an established dialysis-mathematic fitting method. Multicellular spheroids (MCTS) penetration and cytotoxicity were investigated on MCF-7 cell line. Pharmacokinetics of ASL-micelles was evaluated in rats with ASL-solution as control.

Results

The ASL-micelles prepared with DSPE-PEG2000 and TPGS (1:1, w/w) exhibited small size (~18.5 nm), higher EE (~94.12%), better sustained in vitro drug release with lower CMC which may be ascribed to the interaction between drug and carriers. Compared to free ASL, ASL-micelles showed better MCTS penetration capacity and more potent cytotoxicity. Pharmacokinetic studies demonstrated that the half-life and AUC values of ASL-micelles were approximately 1.37-fold and 3.49-fold greater than that of free ASL.

Conclusions

The optimized DSPE-PEG2000/TPGS micelles could serve as a promising vehicle to improve drug retention and penetration in tumor.

KEY WORDS

asulacrine CMC drug retention hybrid micelles multicellular spheroids penetration 

Abbreviations

ASL

Asulacrine

ASL-micelles

Asulacrine micelles

CLSM

Confocal laser scanning microscope

CMC

Critical micelle concentration

DL

Drug loading

DMEM

Dulbecco’s modified Eagle’s media

ECM

Extracellular matrix

EE

Encapsulation efficiency

FBS

Fetal bovine serum

FITC

Fluorescein isothiocyanate isomer I

MCTS

Multicellular tumor spheroids

MTT

3-(4, 5-Dimethylthia-zol-2-yl) -2, 5-diphenyltetrazolium bromide

PDI

Polydispersity index

TEM

Transmission electron microscopy

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

This study was financially supported by the National Science Foundation Grant of China (No. 81503005), the Natural Science Fundation of Jiangsu Province (No. BK20140669), the Priority Academic Program Development of Jiangsu Higher Education Institutions, and National Science and Technology Major Project (No. 2017YFA0205400). The authors declare no competing financial interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ya Jin
    • 1
  • Zimei Wu
    • 2
  • Caibin Li
    • 1
  • Weisai Zhou
    • 1
  • John P. Shaw
    • 2
  • Bruce C. Baguley
    • 3
  • Jianping Liu
    • 1
    Email author
  • Wenli Zhang
    • 1
    Email author
  1. 1.Department of PharmaceuticsChina Pharmaceutical UniversityNanjingPeople’s Republic of China
  2. 2.School of PharmacyUniversity of AucklandAucklandNew Zealand
  3. 3.Auckland Cancer Society Research CentreUniversity of AucklandAucklandNew Zealand

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