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Published on: December 1, 2016
Sorafenib Loaded Inhalable Polymeric Nanocarriers against Non-Small Cell Lung Cancer
Snehal K Shukla1, Nishant S Kulkarni1, Pamela Farrales1
1Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, New York, 11439, USA.
Purpose:
This exploration is aimed at developing sorafenib (SF)-loaded cationically-modified polymeric nanoparticles (NPs) as inhalable carriers for improving the therapeutic efficacy of SF against non-small cell lung cancer (NSCLC).
Methods:
The NPs were prepared using a solvent evaporation technique while incorporating cationic agents. The optimized NPs were characterized by various physicochemical parameters and evaluated for their aerosolization properties. Several in-vitro evaluation studies were performed to determine the efficacy of our delivery carriers against NSCLC cells.
Results:
Optimized nanoparticles exhibited an entrapment efficiency of ~40%, <200 nm particle size and a narrow poly-dispersity index. Cationically-modified nanoparticles exhibited enhanced cellular internalization and cytotoxicity (~5-fold IC50 reduction vs SF) in various lung cancer cell types. The inhalable nanoparticles displayed efficient aerodynamic properties (MMAD ~ 4 μM and FPF >80%). In-vitro evaluation also resulted in a superior ability to inhibit cancer metastasis. 3D-tumor simulation studies further established the anti-cancer efficacy of NPs as compared to just SF.
Conclusion:
The localized delivery of SF-loaded nanoparticles resulted in improved anti-tumor activity as compared to SF alone. Therefore, this strategy displays great potential as a novel treatment approach against certain lung cancers.
