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Design, Synthesis, and Comparison of Pla-Peg-Pla and Peg-Pla-Peg Copolymers for Curcumin Delivery to Cancer Cells Publisher



Rostami N1 ; Faridghiasi F2 ; Ghebleh A3 ; Noei H4 ; Samadzadeh M5 ; Gomari MM6 ; Tajiki A1 ; Abdouss M1 ; Aminoroaya A7 ; Kumari M7 ; Heidari R8 ; Uversky VN9 ; Smith BR7
Authors
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Authors Affiliations
  1. 1. Department of Chemistry, Amirkabir University of Technology, Tehran, 1591634311, Iran
  2. 2. Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, 1449614535, Iran
  3. 3. School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, 8174673461, Iran
  4. 4. Department of Medical Biology and Genetics, Faculty of Medicine, Istinye University, Istanbul, 34010, Turkey
  5. 5. Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, 34010, Turkey
  6. 6. Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, 1449614535, Iran
  7. 7. Department of Biomedical Engineering and Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, 48824, MI, United States
  8. 8. Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, 1411718541, Iran
  9. 9. Department of Molecular Medicine, USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, 33612, FL, United States

Source: Polymers Published:2023


Abstract

Curcumin (CUR) has potent anticancer activities, and its bioformulations, including biodegradable polymers, are increasingly able to improve CUR’s solubility, stability, and delivery to cancer cells. In this study, copolymers comprising poly (L-lactide)-poly (ethylene glycol)-poly (L-lactide) (PLA-PEG-PLA) and poly (ethylene glycol)-poly (L-lactide)-poly (ethylene glycol) (PEG-PLA-PEG) were designed and synthesized to assess and compare their CUR-delivery capacity and inhibitory potency on MCF-7 breast cancer cells. Molecular dynamics simulations and free energy analysis indicated that PLA-PEG-PLA has a higher propensity to interact with the cell membrane and more negative free energy, suggesting it is the better carrier for cell membrane penetration. To characterize the copolymer synthesis, Fourier transform-infrared (FT-IR) and proton nuclear magnetic resonance (1H-NMR) were employed, copolymer size was measured using dynamic light scattering (DLS), and their surface charge was determined by zeta potential analysis. Characterization indicated that the ring-opening polymerization (ROP) reaction was optimal for synthesizing high-quality polymers. Microspheres comprising the copolymers were then synthesized successfully. Of the two formulations, PLA-PEG-PLA experimentally exhibited better results, with an initial burst release of 17.5%, followed by a slow, constant release of the encapsulated drug up to 80%. PLA-PEG-PLA-CUR showed a significant increase in cell death in MCF-7 cancer cells (IC50 = 23.01 ± 0.85 µM) based on the MTT assay. These data were consistent with gene expression studies of Bax, Bcl2, and hTERT, which showed that PLA-PEG-PLA-CUR induced apoptosis more efficiently in these cells. Through the integration of nano-informatics and in vitro approaches, our study determined that PLA-PEG-PLA-CUR is an optimal system for delivering curcumin to inhibit cancer cells. © 2023 by the authors.
1. Peptide-Functionalized Polymeric Nanoparticles for Delivery of Curcumin to Cancer Cells, Journal of Drug Delivery Science and Technology (2024)
8. Plga-Peg-Ra-Based Polymeric Micelles for Tumor Targeted Delivery of Irinotecan, Pharmaceutical Development and Technology (2018)
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