Development of cyclosporine A nanosuspension: cytotoxicity and permeability on Caco-2 cell lines

Abstract

Cyclosporine A is a calcineurin inhibitor and is usually used as an immunosuppressant medication. The main purpose of this study is to develop nanosuspension of polypeptide cyclosporine A by using the wet milling method for oral administration. Cell culture studies were also performed with human intestinal Caco-2 cell lines. Hydroxypropyl methylcellulose and sodium dodecyl sulfate were used as stabilizers in nanosuspension. In vitro characterization studies such as Fourier-transform infrared analysis and morphological imaging with scanning electron microscopy have been carried out with obtained cyclosporine A nanosuspension. The particle size, particle size distribution, and zeta potential values of the nanosuspension were measured approximately 400 nm, 0.4, and −25 mV, respectively. The solubility of cyclosporine A was increased 4.5 times in nanosuspension compared to the coarse cyclosporine A powder. As a result of cytotoxicity studies conducted with different concentrations, it was decided to conduct permeability studies at a dose equivalent to 150 µg/mL cyclosporine A. Permeation studies have shown that the nanosuspension increases cyclosporine A transport by 5 and 1.5 times, respectively, compared to coarse powder and commercial product.

Keywords:

• Cyclosporine A
• nanosuspension
• top-down technology
• Caco-2 cells
• permeability

Acknowledgements

The authors are thankful to Deva Drug Company (İstanbul, Turkey) for providing CsA. The authors also thank to Prof. Dr. İmran Vural for the evaluation of the cytotoxicity and permeability studies.

Disclosure statement

The authors report no conflicts of interest of this paper.

Additional information

Funding

This work was supported by Gazi University Scientific Research Project Foundation [Grant No.: 02/2017-14].