Doxorubicin-loaded micelles of amphiphilic diblock copolymer with pendant dendron improve antitumor efficacy: In vitro and in vivo studies

Voon SH 1 , Kue CS 1 , Imae T 2 , Saw WS 3 , Lee HB 3 , Kiew LV 1 Show all authors , Chung LY 4 , Yusa SI 5

Affiliations 

  • 1 Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 2 Department of Chemical Engineering, National Taiwan University of Science and Technology, 43 Section 4, Keelung Road, Taipei 10607, Taiwan; Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, 43 Section 4, Keelung Road, Taipei 10607, Taiwan. Electronic address: imae@mail.ntust.edu.tw
  • 3 Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 4 Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: chungly@um.edu.my
  • 5 Department of Materials Science and Chemistry, University of Hyogo, 2167 Shosha, Himeji, Hyogo 671-2280, Japan
Int J Pharm, 2017 Dec 20;534(1-2):136-143.
PMID: 29031979 DOI: 10.1016/j.ijpharm.2017.10.023

Abstract

Previously reported amphiphilic diblock copolymer with pendant dendron moieties (P71D3) has been further evaluated in tumor-bearing mice as a potential drug carrier. This P71D3-based micelle of an average diameter of 100nm was found to be biocompatible, non-toxic and physically stable in colloidal system up to 15days. It enhanced the in vitro potency of doxorubicin (DOX) in 4T1 breast tumor cells by increasing its uptake, by 3-fold, compared to free DOX. In 4T1 tumor-bearing mice, the tumor growth rate of P71D3/DOX (2mg/kg DOX equivalent) treated group was significantly delayed and their tumor volume was significantly reduced by 1.5-fold compared to those treated with free DOX. The biodistribution studies indicated that P71D3/DOX enhanced accumulation of DOX in tumor by 5- and 2-fold higher than free DOX treated mice at 15min and 1h post-administration, respectively. These results suggest that P71D3 micelle is a promising nanocarrier for chemotherapeutic agents.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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