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Original Article



Preparation of zinc oxide-carboxymethyl cellulose blended with cyclophosphamide for targeted drug delivery to lung adenocarcinoma cells

K. Harsha Prabha, Mahalakshmi Nannan, Sivaramakrishnan Venkatabalasubramanian.




Abstract

Lung adenocarcinoma represents more than 40% of global lung cancer cases diagnosed yearly. Nano-drug delivery systems made from polymeric nanocomposites (NCs) have been described as promising carriers of chemotherapeutic payload against lung adenocarcinoma. Zinc oxide (ZnO) nanoparticles, which have been shown to produce tumor-selective cell death, lower treatment resistance, and lower side effects in vitro, are excellent therapeutic systems that can be combined with chemotherapeutic agents. Using the chemical reduction method, we prepared ZnO nanoparticles in this study and embedded them in non-toxic adsorbent carboxymethyl cellulose (CMC). This polymeric nanocomposite (NC) was further blended with cyclophosphamide (CPS): A hydrophobic chemotherapeutic drug and analyzed for its cytotoxicity against lung adenocarcinoma cells. Characterization of NCs was performed by UV-visible spectroscopy, dynamic light scattering, Fourier-transform-infrared spectroscopy, and transmission electron microscopy. MTT analysis revealed that the biological cytotoxic potential of ZnO-CMC-CPS NCs was superior to ZnO-CMC NCs against A549 cells. Furthermore, Western blot analysis for Ki-67 (proliferation biomarker) expression analysis was performed for ZnO entrapped CMC NC versus ZnO-CMC-CPS-treated lung adenocarcinoma cells. ZnO-CMC-CPS NCs revealed a superior decrease in Ki-67 expression compared to ZnO-CMC alone treated lung adenocarcinoma cells. These results indicate that the synthesized ZnO-CMC-CPS polymeric NC, compared to ZnO-CMC, is an efficient drug delivery system with anti-proliferative potential and augmented cytotoxicity against lung adenocarcinoma cells. These polymeric NCs are prospective drug delivery systems for antiproliferative therapy.

Key words: Polymeric Nanocomposites, Lung cancer, Cyclophosphamide, Carboxymethyl cellulose, Zinc Oxide






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