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

Gülbağ Pınar S., Pezik E., Mutlu Ağardan B., Çelebi N.

Pharmaceutical Development and Technology, vol.27, no.1, pp.52-62, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 27 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1080/10837450.2021.2020817
  • Journal Name: Pharmaceutical Development and Technology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Business Source Elite, Business Source Premier, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, MEDLINE
  • Page Numbers: pp.52-62
  • Keywords: Cyclosporine A, nanosuspension, top-down technology, Caco-2 cells, permeability
  • Hacettepe University Affiliated: Yes


© 2021 Informa UK Limited, trading as Taylor & Francis Group.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.