Oral inhalation of dacomitinib nanocarriers as a therapeutic strategy for non-small cell lung cancer

Abstract

Background: Development of an inhalable nanoformulation of dacomitinib (DMB) encapsulated in poly-(lactic-co-glycolic acid) nanoparticles (NPs) to improve solubility, facilitate direct lung delivery and overcome the systemic adverse effects. Methods: DMB-loaded poly-(lactic-co-glycolic acid) NPs were prepared using solvent evaporation and characterized for particle size, polydispersity index and zeta-potential. The NPs were evaluated for in vitro drug release, aerosolization performance and in vitro efficacy studies. Results: The NPs showed excellent particle characteristics and displayed a cumulative release of ∼40% in 5 days. The NPs demonstrated a mass median aerodynamic diameter of ∼3 μm and fine particle fraction of ∼80%. Further, in vitro cell culture studies showed improved cytotoxic potential of DMB-loaded NPs compared with free drug. Conclusion: The study underscores the potential of DMB-loaded NPs as a viable approach for non-small cell lung cancer treatment.

GRAPHICAL ABSTRACT

Keywords: :

• dacomitinib
• FPF (fine particle fraction)
• inhaled therapy
• MMAD (mass median aerodynamic diameter)
• nanoparticles

Acknowledgments

DSR and SMP were supported through teaching assistantships from the Department of Pharmaceutical Sciences, CPHS, St. John's University. All authors declare no conflict of interest in this work. Part of this work has been presented as a conference abstract/proceeding at Drug Delivery to the Lungs Volume 32, 2021 and the copyright remains with authors.

Author contributions

DSR did the conceptualization, methodology, validation, formal analysis, data curation, investigation, visualization and writing (original draft, review and editing). SMP did the methodology, visualization, writing (review and editing). NKK did the conceptualization, methodology, writing (original draft, review and editing), resources, supervision, project administration and funding acquisition.

Financial disclosure

The authors have no 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.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity 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.

Writing disclosure

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