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Synthesis, in Vitro Characterization, and Anti-Tumor Effects of Novel Polystyrene-Poly(Amide-Ether-Ester-Imide) Co-Polymeric Micelles for Delivery of Docetaxel in Breast Cancer in Balb/C Mice Publisher Pubmed



Varshosaz J1 ; Enteshari S1 ; Hassanzadeh F2 ; Hashemibeni B3 ; Minaiyan M4 ; Mirsafaei R1
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Pharmaceutical Chemistry, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Anatomical Sciences and Dental Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Department of Pharmacology, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Drug Development and Industrial Pharmacy Published:2018


Abstract

Objective: The goal of the present work was to make novel co-polymeric micellar carriers for the delivery of docetaxel (DTX). Significance: Co-polymeric micelles can not only solubilize DTX and eliminate the need for toxic surfactants to dissolve it, but also cause passive targeting of the drug to the tumor and reduce its toxic side effects. Methods: Poly(styrene-maleic acid) (SMA) was conjugated to poly (amide-ether-ester-imide)-poly ethylene glycol (PAEEI-PEG). Copolymer synthesis was proven by Fourier transform infrared (FTIR) and 1H-nuclear magnetic resonance (1H-NMR). The SMA-PAEEI-PEG micelles loaded with DTX were prepared and their critical micelle concentration (CMC), zeta potential, particle size, entrapment efficiency, and their release efficiency were studied. MCF-7 and MDA-MB231 breast cancer cells were used to evaluate the cellular uptake and cytotoxicity of the micelles. The antitumor activity of the DTX-loaded nanomicelles was measured in Balb/c mice. Results: The FTIR and HNMR spectroscopy confirmed successful conjugation of SMA and PAEEI-PEG. The drug loading efficiency was in the range of 34.01–72.75% and drug release lasted for 120 h. The CMC value of the micelles was affected by the SMA/PAEEI-PEG ratio and was in the range of 29.85–14.28 µg/ml. The DTX-loaded micelles showed five times more cytotoxicity than the free drug. The DTX loaded micelles were more effective in tumor growth suppression in vivo and the animals showed an enhanced rate of survival. Conclusion: The results show that the SMA-PAEEI-PEG micelles of DTX could potentially provide a suitable parenteral formulation with more stability, higher cytotoxicity, and improved antitumor activity. © 2018 Informa UK Limited, trading as Taylor & Francis Group.
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