pH-Controlled multiple-drug delivery by a novel antibacterial nanocomposite for combination therapy

Abstract

Nanoparticle-based combination therapies have shown several unique features that are untenable in traditional chemotherapy. The present attempt intends to prepare a novel smart multifunctional drug delivery system based on cationic silica based polymer–clay nanocomposites for combination cancer therapy. The intercalation of silica based copolymers into montmorillonite (MMT) was achieved through an ion exchange process. The structure of the resulting nanocomposites was characterized by means of XRD, FT-IR, TG-DTA and SEM. This nanocomposite was used for multiple drug delivery of two anticancer drugs doxorubicin (DOX) and methotrexate (MTX) and an antibacterial agent ciprofloxacin (CIP). The in vitro antimicrobial activity of nanocomposites and CIP loaded nanocomposites was tested in growth inhibition of Escherichia coli and Pseudomonas aeruginosa bacteria by the MIC method. Furthermore, the potential antitumoral activity of this combined therapy system was evaluated against T47D cell lines by MTT assay and qRT-PCR. XRD results proved successful interaction of MMT with the cationic silica based copolymer. The nanocomposites showed an encapsulation efficiency of about 95% for the mentioned drugs. The cumulative in vitro release of the DOX/MTX/CIP-loaded nanocomposites revealed that the individual drug can undergo controlled release with the ability to distinguish between tumor tissues. Cell viability tests additionally confirmed that the dual-administration of DOX with MTX had a higher cytotoxicity to the mentioned cells in comparison with free dual drug forms. The in vitro antimicrobial results revealed good antimicrobial activities of both the blank nanocomposite and CIP loaded nanocomposite. Therefore, the dual anticancer drug-loaded antibacterial smart nanocomposite has the potential to be used for combination cancer therapy.