Inhalable spray-dried polycaprolactone-based microparticles of Sorafenib Tosylate with promising efficacy on A549 cells

Abstract

The study developed and evaluated Sorafenib Tosylate (SRT)-loaded polymeric microparticles (MPs) using biodegradable polymer polycaprolactone (PCL) as a potential inhalable carrier for NSCLC. MPs were prepared by spray-drying an oil-in-water (o/w) emulsion. The optimized MPs demonstrated excellent flowability, particle size of 2.84 ± 0.5 μm, zeta potential of −14.0 ± 1.5 mV, and 85.08 ± 5.43% entrapment efficiency. ATR-FTIR/DSC studies revealed a lack of characteristic peaks of the crystalline drug signifying good entrapment of the drug. MPs were spherical and uniform in SEM pictures. The MPs showed a biphasic release pattern up to 72h. The Anderson cascade impactor (ACI) investigation demonstrated the highest drug deposition at stage 4, which revealed that the MPs can reach the lungs’ secondary and terminal bronchi. Inhalable MPs had an efficient aerodynamic property with a mass median aerodynamic diameter (MMAD) of 2.63 ± 1.3 μm, a geometric standard deviation (GSD) of 1.93 ± 0.2 μm, and a fine particle fraction (FPF) of 87 ± 2.5%. Finally, in cytotoxicity studies on A549 cancer cells, MPs had an IC₅₀ value of 0.6011 ± 0.8 μM, which was 85.68% lower than free drug. These findings suggest SRT-loaded inhalable PCL-based MPs as a novel NSCLC treatment.

Keywords:

• Sorafenib tosylate
• non-small cell lung cancer
• inhalable
• polycaprolactone
• microparticles
• A549 cell line

Acknowledgments

ACG Associated Capsules Pvt. Ltd., Mumbai is duly acknowledged for providing empty hard-shell capsules. The authors thank Bombay College of Pharmacy, Mumbai for providing the Andersen cascade impactor (ACI) facility.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.