Exploration of Nanomedicine-Based Dry Powder Inhalation Formulation Co-Loaded with Erlotinib and Curcumin for Treatment of Non-Small Cell Lung Cancer

Erlotinib is used as first-line chemotherapy for the treatment of non-small cell lung cancer (NSCLC), which accounts for approximately 85% of lung cancers. Curcumin has potential antitumor effects in different types of cancer including NSCLS with additional chemopreventive and radioprotective effects. The aim of the study was to develop erlotinib and curcumin co-loaded dry powder inhalation (EC-DPI) formulation using nanoprecipitation technique with a goal of achieving a stronger cytotoxic effect against A549 cancer cells. The optimized DPI formulation resulted in suitable particle size (313.28 +/- 26.19 nm), polydispersity index (0.156 +/- 0.016) and zeta potential (29.4 +/- 1.22 mV). Carr's index (6.62 +/- 1.43) and Hausner ratio (1.058 +/- 0.03) demonstrated excellent flowability of the powder. The fine particle fraction (64.7 +/- 7.8%) and mass median aerodynamic diameter (2.98 +/- 0.04 mu m) of the optimized formulation revealed good aerosol performance and its suitability for direct delivery to the lungs. In-vitro cytotoxic potential of EC-DPI was determined against A549 cancer cells and compared with curcumin-loaded DPI formulation (C-DPI) and erlotinib-loaded DPI formulation (E-DPI). The IC50 values for E-DPI and C-DPI were found to be 36.6 +/- 2.4 mu M and 24.4 +/- 2.7 mu M, respectively. The IC50 value for EC-DPI was 20.5 +/- 2.1 mu M confirming the synergistic effect of both drugs against A549 cancer cells. The internalization of the drug inside A549 cells was detected by a cellular uptake study. The EC-DPI demonstrated the highest cellular uptake (0.07 +/- 0.006 ng/mu g) followed by the formulation containing curcumin (0.05 +/- 0.003 ng/mu g) and erlotinib (0.03 +/- 0.004 ng/mu g) alone at the end of 6 h. Hence, the developed DPI formulation can be considered as a potential therapeutic approach for the direct delivery of erlotinib and curcumin to treat NSCLC.