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. 2021 Mar 26;26(7):1889.
doi: 10.3390/molecules26071889.

Chitosan Membranes Filled with Cyclosporine A as Possible Devices for Local Administration of Drugs in the Treatment of Breast Cancer

Sonia Trombino  1 , Federica Curcio  1 , Teresa Poerio  2 , Michele Pellegrino  1 , Rossella Russo  1 , Roberta Cassano  1
Affiliations

Chitosan Membranes Filled with Cyclosporine A as Possible Devices for Local Administration of Drugs in the Treatment of Breast Cancer

Sonia Trombino et al. Molecules. .

Abstract

The aim of this work is the design, preparation and characterization of membranes based on cyclosporine A (CsA) and chitosan carboxylate (CC) to be used as an implantable subcutaneous medical device for a prolonged therapeutic effect in the treatment of breast cancer. The choice to use CsA is due to literature data that have demonstrated its possible antitumor activity on different types of neoplastic cells. To this end, CsA was bound to CC through an amidation reaction to obtain a prodrug to be dispersed in a chitosan-based polymeric membrane. The reaction intermediates and the final product were characterized by Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H-NMR). Membranes were analyzed by differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The data obtained showed the effective formation of the amide bond between CsA and CC and the complete dispersion of CsA inside the polymeric membrane. Furthermore, preliminary tests, conducted on MDA-MB-231, a type of breast cancer cell line, have shown a high reduction in the proliferation of cancer cells. These results indicate the possibility of using the obtained membranes as an interesting strategy for the release of cyclosporin-A in breast cancer patients.

Keywords: breast cancer; carboxylated chitosan; chitosan; cyclosporine A; membrane.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scheme of CsACC synthesis.
Figure 1
Figure 1
Scheme of CsACC synthesis.
Figure 2
Figure 2
FT-IR of CsACC (a), CC (b), CsA (c).
Figure 3
Figure 3
1H-NMR spectrum of CsACC.
Figure 4
Figure 4
DSC curve of CsACC (a), CC (b).
Figure 5
Figure 5
FT-IR of membrane based on chitosan (a), chitosan + CsACC (b).
Figure 6
Figure 6
SEM photomicrographies of the membrane based on chitosan (a), and chitosan + CsACC (b). The images are taken at 10 K× magnification.
Figure 7
Figure 7
Confocal imagine of chitosan membrane (CTR), membrane based on free CsA containing coumarin-6 (a), and membrane based on CsACC containing cumarin-6 (b).
Figure 8
Figure 8
Cell proliferation assay on MDA-MB-231 cell lines of chitosan membranes with and without CsA.
See this image and copyright information in PMC

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