| Autor: |
Garcia BBM; Department of Biophysics, Paulista School of Medicine, Federal University of São Paulo, 04023-062 São Paulo, Brazil.; Pharmaceutics Division, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands., Douka S; Pharmaceutics Division, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands., Mertins O; Department of Biophysics, Paulista School of Medicine, Federal University of São Paulo, 04023-062 São Paulo, Brazil., Mastrobattista E; Pharmaceutics Division, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands., Han SW; Department of Biophysics, Paulista School of Medicine, Federal University of São Paulo, 04023-062 São Paulo, Brazil. |
| Abstrakt: |
Cationic lipid-based carriers are recognized for their ability to complex with mRNA and effectively deliver the mRNA for vaccination and therapeutic purposes. However, the significant cytotoxicity of these carriers often restricts their practical application. In the present study, polymer-lipid hybrid nanoparticles, termed chitosomes, incorporating chitosan-N-arginine (CSA) with the DOTAP cationic lipid and the DOPE helper lipid, were synthesized and evaluated. The addition of CSA to the lipid formulations improved their physicochemical stability and enhanced mRNA complexation, resulting in high transfection rates in the HeLa and HEK293T cell lines. However, the transfection efficiency was low in the NIH-3T3 cell line, indicating a cell type-specific response to chitosomes. Importantly, CSA significantly reduced the cytotoxicity typically associated with DOTAP. Overall, the present study indicated that optimizing the ratio of CSA to DOTAP is crucial for developing mRNA nanocarriers to achieve high transfection efficiency and reduce cytotoxicity across different cell lines. |
