Inhalable Cationic Niosomes of Curcumin Enhanced Drug Delivery and Apoptosis in Lung Cancer Cells

Abstract

Background: Curcumin induces apoptosis in non-small cell lung cancer cells. Hence, inhalable cationic niosomes of curcumin were developed to surmount the poor physicochemical and biopharmaceutical limitations for effective drug delivery in lung cancer cells.Methods: Curcumin loaded freeze-dried cationic small unilamellar niosomes (Cur-C-SUNS) were prepared using reverse phase evaporation method and characterized in vitro using spectral, analytical and biological techniques.Results: The nanovesicle size, encapsulation efficiency and zeta-potential of Cur-C-SUNS were measured to be 97.4±8.3 nm, 83.3±5.1% and +28.5±1.25 mV, significantly (P<0.05) higher than 83.8±7.2 nm, 78.8±4.5% and -3.02±0.64 mV of optimized freeze-dried Cur-SUNS. Cur-C-SUNS inhibited the A549 lung cancer cells proliferation at the IC50 of 3.1 μM, significantly (P<0.05) lower than 7.5 μM of Cur-SUNS and curcumin suspension (<32 μM). Consistently, Cur-C-SUNS induced greater extent of apoptosis in comparison to Cur-SUNS and curcumin suspension. In addition, Cur-C-SUNS accumulated significantly (P<0.05) higher concentration of curcumin, 14.3±2.1 μg in A549 cells, as compared to 9.5±1.5 μg and 1.3±0.2 μg deposited, respectively by Cur-SUNS and curcumin suspension. At last, in vitro cellular uptake illustrated higher endocytosis of Cur-C-SUNS as compared to Cur-SUNS due to electrostatic interaction between cationic nanovesicles and negatively charged plasma membrane of A549 cells.Conclusion: In conclusion, promising in vitro attributes of Cur-C-SUNS in lung cancer therapy warrant further in vivo tumor regression study to scale up the technology for clinical translation.

Keywords: Curcumin; Inhalation; Cationic niosomes; Lung cancer cells; Cytotoxicity; Apoptosis; Cellular uptake