Abstract

This study aims to improve the cytotoxicity and potency of cisplatin-loaded polybutylcyanoacrylate (PBCA) nanoparticles (NPs) for the treatment of lung cancer through the modulation of temperature and polyethylene glycol (PEG) concentration as effective factors affecting the NPs’ properties. The NPs were synthesized using an anionic polymerization method and were characterized in terms of size, drug loading efficiency, drug release profile, cytotoxicity effects, drug efficacy, and drug side effects. In this regard, dynamic light scattering (DLS), scanning electron microscopy (SEM), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) methods, and hematoxylin and eosin (H&E) staining were used. The results showed that the size and the drug loading efficiency of the synthesized spherical NPs were 355–386 nm and 14–19%, respectively. Also, the drug release profile showed a controlled and slow drug release pattern with approximately 10% drug release over 48 h. In addition, the NPs significantly increased the cytotoxicity of the cisplatin in vitro environment by approximately 2 times and enhanced the therapeutic effects of the drug in vivo environment by increasing the survival time of lung-cancer-bearing mice by 20% compared to the standard drug receiver group. Also, the nanoformulation decreased the drug toxicity in an in vivo environment. According to the results, increasing the temperature and PEG concentration improved the properties of the drug loading efficiency, drug release profile, and cytotoxicity effect of drug-loaded NPs. Consequently, the synthesized formulation increased the survival of tumor-bearing mice and simultaneously decreased the cisplatin toxicity effects. In conclusion, the prepared nanoformulation can be considered a promising candidate for further evaluation for possible therapeutic use in the treatment of lung cancer.

Highlights

  • Cisplatin is an anticancer drug and is widely used in the treatment of solid tumors, such as testicular, cervical, ovarian, head and neck, and lung cancer [1,2,3]

  • Cisplatin-loaded PBCA NPs were successfully synthesized by the dropwise addition of BCA monomer into the polymerization medium

  • The temperature was set by a thermometer; 10 min after monomer addition, the color of the medium was changed from colorless to milky, implying monomer polymerization

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Summary

Introduction

Cisplatin is an anticancer drug and is widely used in the treatment of solid tumors, such as testicular, cervical, ovarian, head and neck, and lung cancer [1,2,3]. Cisplatin binds to the N7-positions of guanosine bases in deoxyribonucleic acid (DNA) molecules and disrupts DNA replication, leading to cell death [4]. Targeted delivery of cisplatin can significantly improve its efficacy and simultaneously decrease the side effects of cisplatin. In this regard, nanodrug delivery systems such as polybutylcyanoacrylate (PBCA) nanoparticles (NPs) are considered an appropriate strategy and have received considerable attention as they increase drugs’ specificity and reduce their side effects [7]

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