Amelioration of The Therapeutic Potential of Gefitinib Against Breast Cancer Using Nanostructured Lipid Carriers

Abstract

Aim: This study aimed to improve the delivery and therapeutic potential of gefitinib (GTB) against breast cancer by preparing GTB-loaded, nanostructured lipid carriers (GTB-NLCs). Materials & methods: Box–Behnken design was used for optimization and GTB was loaded into NLCs using ultrasonication. The GTB-NLCs were characterized using in vitro, ex vivo and in vivo studies. The anticancer efficacy of GTB-NLCs was evaluated using 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity and flow cytometry on MCF-7 breast cancer cell lines. Results: Optimized GTB-NLCs were successfully characterized and demonstrated improved internalization and enhanced cytotoxicity compared with plain GTB. Gut permeation studies showed enhanced intestinal permeability, and pharmacokinetic analysis revealed 2.6-fold improvement in GTB oral bioavailability. Conclusion: GTB-NLCs effectively enhanced the therapeutic potential of GTB against breast cancer.

Plain language summary

Gefitinib is an important drug approved for the treatment of cancer. However, there are issues with gefitinib, including its low water solubility and toxicity. Being poorly water soluble, the absorption of gefitinib in blood is low and therefore high doses are required to achieve the therapeutic level. Also, gefitinib is nonselective for cancer as well as noncancer cells, leading to toxicity on other organs. This study aimed to incorporate gefitinib into a lipid-based carrier, which improved its properties such as solubility, stability and bioavailability. The prepared formulation was tested for its drug release, stability and efficacy on breast cancer cell lines as well as toxicity using various methods. It was observed that the prepared formulation not only improved bioavailability but also improved the targeting as more gefitinib entered the cancer cells when present in the formulation, decreasing the toxicity of gefitinib on other organs. In conclusion, the prepared formulation can be regarded as an effective approach to improving the therapeutic potential of gefitinib.

Keywords::

• anticancer
• Box–Behnken design
• breast cancer
• characterization
• gefitinib
• nanostructured lipid carriers
• optimization

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/nnm-2023-0107

Financial & competing interests disclosure

The authors report no conflicts of interest. The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

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

Ethical conduct of research

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 animal experimental investigations. All rats were approved through Committee for the Purpose of Control and Supervision of Experiments on Animals guidelines by the Institutional Ethics Committee at Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, India, with protocol no. IEAC/2022/I-R05.

Additional information

Funding

The authors report no conflicts of interest. The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.