Minimizing Cytotoxic Effects on Normal Cells: Enhanced Targeted Delivery of Docetaxel via PCL-PEG-PCL Nanocarriers in Breast Cancer Treatment
نویسندگان
1 Department of Clinical Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran
2 Department of Immunology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
3 Pharmaceutical Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
4 Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
5 Student Research Committee, Babol University of Medical Sciences, Babol, Iran
6 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
7 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
doi
10.22090/jwent.2025.04.007چکیده
Nanoparticle-based drug delivery systems are rapidly advancing in cancer therapy, providing reduced toxic side effects and improved efficacy through controlled drug release. This study encapsulated docetaxel (DTX) in a PCL-PEG-PCL matrix using a modified nano-precipitation method, focusing on its cytotoxic effects on breast cancer cell lines. The research aimed to clarify the mechanisms behind the cytotoxic effects and cell death induced by DTX-loaded nano-carriers, utilizing human breast cancer cell lines as an experimental model. The synthesized nano-carriers were characterized through methods such as transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic light scattering (DLS). Drug release kinetics and encapsulation efficiency were evaluated with high-performance liquid chromatography (HPLC) and dialysis techniques. The cytotoxicity of DTX-loaded nano-carriers and free DTX was assessed in MCF-7, MDA-MB-231, and fibroblast cell lines over 48 and 72 hours using MTT assays to measure viability and Hoechst 33342 staining for apoptosis. Results showed that nano-carriers significantly inhibited cell growth in MCF-7 and MDA-MB-231 cells, especially with formulation P1 over 72 hours, compared to 48 hours. Apoptosis assays confirmed the effective induction of cell death by nano-carriers. The IC50 values for formulation P1 were substantially higher after 72 hours. Overall, these findings suggest that the designed nano-carriers promote controlled drug release and enhance apoptotic cell death while reducing the toxic side effects of docetaxel on normal cells, highlighting their potential in cancer therapeutics.
