Formulation and In Vivo Efficacy Study of Cetuximab Decorated Targeted Bioadhesive Nanomedicine for Non-Small-Cell Lung Cancer Therapy

Abstract

Aim: To design, optimize and evaluate docetaxel-loaded chitosan nanoparticles with (targeted) and without (nontargeted) cetuximab conjugation for the treatment of non-small-cell lung cancer (NSCLC). Materials & methods: Risk-assessment, optimization, in vitro characterizations, stability assessments, release studies, cell-culture studies were performed along with histopathology, pharmacokinetic and anticancer efficacy studies. Results: The nanoparticles of desired particle size (152.59 ± 3.90 nm to 180.63 ± 5.21 nm) which could sustain drug release for up to 70 h, were obtained. The cell-culture studies demonstrated the superiority of the formulations over Docel™. The pharmacokinetic evaluation showed the excellent systemic bioavailability of prepared NPs. The histopathology screening revealed lesser toxicity of both the nontargeted and targeted formulations. The targeted nanoformulation significantly reduced tumor growth than the nontargeted formulation and Docel. Conclusion: These results demonstrate the therapeutic potential of the prepared nanoformulation. After proper clinical validation, it could be a promising approach for the treatment of NSCLC.

Keywords::

• bioadhesive nanomedicine
• cetuximab
• chitosan
• EGFR receptor
• lung cancer

Supplementary data

To view the supplementary data that accompany this article please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/nnm-2020-0167

Author contributions

MK Viswanadh designed and performed the experiments. Vikas and A Jha assisted in performing the experiments and collecting data. SK Reddy Adena assisted in the optimization of formulation. AK Mehata assisted in preparing the article. V Priya assisted in the preparation of necessary figures. K Neogi assisted in the cell culture related experiments and in vivo studies. S Poddar helped with fluorescence imaging and arrangement of results. SK Mahto helped in designing in vitro experiments on cell lines such as uptake, cytotoxicity and migration studies and helped with the fluorescent microscope and bright field microscope facilities. MS Muthu supervised the research, critical revision and final approval of the version. All the co-authors together with MS Muthu are accountable for all aspects of the work in ensuring questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Financial & competing interests disclosure

The authors are grateful to Ministry of Human Resources and Development, New Delhi for financial support in the form of teaching assistantship conferred by Indian Institute of Technology (Banaras Hindu University), Varanasi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

Institutional Animal Ethical Committee (no. Dean/2019/IAEC/1245) of Institute of Medical Sciences, Banaras Hindu University, Varanasi approved the experimental protocol. The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Additional information

Funding

The authors are grateful to Ministry of Human Resources and Development, New Delhi for financial support in the form of teaching assistantship conferred by Indian Institute of Technology (Banaras Hindu University), Varanasi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.