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Research Article

Novel Methotrexate-Ciprofloxacin Loaded Alginate-Clay Based Nanocomposite as Anticancer and Antibacterial Co-Drug Delivery System

Mehrdad Mahkam, Fatemeh Bazmi Zeynabad, Effat Alizadeh, Mahdi Rahimi, Fariborz Rahimi, Roya Salehi* ORCID logo

Abstract

Purpose: In last decades, by increasing multi-drug resistant microbial pathogens an urgent demand was felt in the development of novel antimicrobial agents. Methods: Promising nanocomposites composed of clay/alginate/imidazolium-based ionic liquid, have been developed via intercalation of calcium alginate and ionic liquid by ion-exchange method. These tailored nanocomposites were used as nanocarriers to simultaneously deliver methotrexate (MTX), and ciprofloxacin (CIP), as anticancer and antibacterial agents, respectively to MCF-7 breast cancer cells. Nanocomposites were fully characterized by SEM, XRD, FTIR spectroscopy, and TGA methods. The in vitro antimicrobial potential of the mentioned nanocomposites in free and dual-drug loaded form was investigated on Pseudomonas aeruginosa and Escherichia coli bacteria. The antitumor activity of nano-formulations was evaluated by both MTT assay and cell cycle arrest. Results: The dual drug-loaded nanocomposites with exceptionally high loading efficiency (MTX: 99 ±0.4% and CIP: 98 ±1.2%) and mean particle size of 70 nm were obtained with obvious pH-responsive MTX and CIP release (both drugs release rate was increased at pH 5.8 compared to 7.4). The antibacterial activity of CIP-loaded nanocomposites was significantly higher in comparison with free CIP (p <0.001). The antitumor activity results revealed that MTX cytotoxicity on MCF-7 cells was significantly higher in nano-formulations compared to free MTX (p <0.001). Both MTX-loaded nanocomposites caused S-phase arrest in MCF-7 cells compared to non-treated cells (P˂0.001). Conclusion: Newly developed smart nanocomposites are potentially effective pH-sustainable delivery systems for enhanced tumor therapy.
Keywords: Drug delivery system, alginate, nanoclay, pH-sensitive nanocomposite, cancer therapy, antibacterial activity
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Submitted: 14 Sep 2019
Revision: 22 May 2020
Accepted: 30 Jun 2020
ePublished: 01 Jul 2020
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