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

(2018) 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. Drug Development and Industrial Pharmacy. pp. 1139-1157. ISSN 0363-9045

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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 H-1-nuclear magnetic resonance (H-1-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 mg/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.

Item Type: Article
Keywords: polystyrene-poly(amide-ether-ester-imide)-poly(ethylene glycol) micelle docetaxel breast cancer antitumor activity poly(styrene-co-maleic acid) drug-release nanoparticles therapy copolymer nanocarriers nanocapsules paclitaxel toxicity carriers
Divisions: Dental Research Center
Faculty of Medicine > Department of Basic Science > Department of Anatomical Sciences
Faculty of Pharmacy and Pharmaceutical Sciences > Department of Pharmacotherapy
Faculty of Pharmacy and Pharmaceutical Sciences > Department of Toxicology and Pharmacology
Novel Drug Delivery Systems Research Center
Faculty of Pharmacy and Pharmaceutical Sciences > گروه شیمی دارویی
Page Range: pp. 1139-1157
Journal or Publication Title: Drug Development and Industrial Pharmacy
Journal Index: ISI
Volume: 44
Number: 7
Identification Number: https://doi.org/10.1080/03639045.2018.1438462
ISSN: 0363-9045
Depositing User: Zahra Otroj
URI: http://eprints.mui.ac.ir/id/eprint/7011

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