Simultaneous pulmonary administration of celecoxib and naringin using a nebulization-friendly nanoemulsion: A device-targeted delivery for treatment of lung cancer

ABSTRACT

Background

Lung cancer is a principal cause of death worldwide, and its treatment is very challenging. Nebulization offers a promising means of targeting drugs to their site of action in the lung.

Research design and methods

In the present study, nebulizable oil in water nanoemulsion formulations was co-loaded with naringin/celecoxib and tested for pulmonary administration by different nebulizer types.

Results

The translucent appearance of nanoemulsion formulations was revealed, with particle size (75–106 nm), zeta potential (−3.42 to −4.86 mV), and controlled in-vitro release profiles for both drugs. The nanoemulsions showed favorable stability profiles and superior cytotoxicity on A549 lung cancer cells. Aerosolization studies on the selected nanoemulsion formulation revealed its high stability during nebulization, with the generation of an aerosol of small volume median diameter and mass median aerodynamic diameter lower than 5 µm. Moreover, it demonstrated considerable safety and bioaccumulation in lung tissues, in addition to accumulation in the brain, liver, and bones, which are the main organs to which lung cancer metastasizes.

Conclusions

Nanoemulsion proved to be a promising nebulizable system, which paves the way for treatment of pulmonary diseases other than lung cancer.

KEYWORDS:

• Celecoxib
• lung cancer
• nanoemulsion
• naringin
• nebulizer
• pulmonary

Acknowledgments

The authors are sincerely grateful to Gattefosse Company, France, for supplying Labrafac Lipophile and Amoun pharmaceutical industries Co., Egypt, for their kind supply of celecoxib.

Declaration 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here

Author contributions

All authors were involved in the conception, design, analysis, and interpretation of data, as well as drafting the paper and its critical revision. All authors agree to be accountable for all aspects of the work, and they all approve the final version of the paper.

Additional information

Funding

This work was funded by The Science and Technology Development Fund (STDF) in Egypt (Project ID 6087, Short Term Fellowship (STF), code TC/14/STF/2013/6087).