Sorafenib Loaded Inhalable Polymeric Nanocarriers against Non-Small Cell Lung Cancer

• DOI: 10.1007/s11095-020-02790-3
• Publication Date: 2020-03-12T19:04:30Z
• Authors: Snehal K. Shukla; Nishant S. Kulkarni; Pamela Farrales; Dipti D. Kanabar; Vineela Parvathaneni; Nitesh K. Kunda; Aaron Muth; Vivek Gupta
• Keywords: 0301 basic medicine; Drug Carriers; Lung Neoplasms; Polymers; Antineoplastic Agents; Sorafenib; 3. Good health; 03 medical and health sciences; Carcinoma, Non-Small-Cell Lung; Cations; Cell Line, Tumor; Administration, Inhalation; Humans; Nanoparticles; Particle Size

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).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.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.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.