Dual Loading of Trans-Cinnamaldehyde and Either Paclitaxel or Curcumin in Chitosan Nanoparticles: Physicochemical Characterization and Biological Evaluation Against MDCK and HeLa Cells

Biopolymer chitosan sub-micron particles (CSMPs) were prepared by the ionic gelation technique crosslinked with sodium tripolyphosphate co-loaded with trans-cinnamaldehyde (TCIN), and either curcumin (CUR) or paclitaxel (PTX). The size of the spherical CSMPs increased from 118 nm to 136 nm and 170 nm after the loading of TCIN and CUR, whereas the loading of PTX led to a slight decrease (114 nm). Polydispersity indexes of all the samples were smaller than 0.4, indicating monodisperse particles. Zeta potential values higher than +40 mV were determined, which is direct proof of the high stability of these nanoparticles. TCIN and PTX release studies in vitro, at pH 6.5 and 7.4, showed a pH dependence on the release rate with a higher value at pH 6.5. However, CUR was not released from CSMPs probably due to strong interactions with CS biopolymer chains. Cytotoxicity studies showed that the systems loaded with TCIN and PTX were more cytotoxic for HeLa cancer cells than for MDCK cells. Moreover, a synergistic effect against HeLa cells was observed for the TCIN-PTX-loaded CSMP samples. The Sensitivity Index indicated that the CSMPs loaded with TCIN have a prospective attraction to carry and release conventional or new chemotherapeutic drugs. This study demonstrates the in vitro efficiency of the obtained drug delivery system, but in vivo studies are necessary to confirm its potential for clinical applications.