Design, Synthesis, and Comparison of PLA-PEG-PLA and PEG-PLA-PEG Copolymers for Curcumin Delivery to Cancer Cells
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-P...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/15/14/3133 |
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| author | Neda Rostami Farzaneh Faridghiasi Aida Ghebleh Hadi Noei Meisam Samadzadeh Mohammad Mahmoudi Gomari Alireza Tajiki Majid Abdouss Alireza Aminoroaya Manisha Kumari Reza Heidari Vladimir N. Uversky Bryan R. Smith |
| author_facet | Neda Rostami Farzaneh Faridghiasi Aida Ghebleh Hadi Noei Meisam Samadzadeh Mohammad Mahmoudi Gomari Alireza Tajiki Majid Abdouss Alireza Aminoroaya Manisha Kumari Reza Heidari Vladimir N. Uversky Bryan R. Smith |
| author_sort | Neda Rostami |
| collection | DOAJ |
| description | 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 (<sup>1</sup>H-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 (IC<sub>50</sub> = 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. |
| first_indexed | 2024-03-11T00:42:16Z |
| format | Article |
| id | doaj.art-ac69cca45443448891ee4492f86b758b |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-11T00:42:16Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-ac69cca45443448891ee4492f86b758b2023-11-18T21:03:45ZengMDPI AGPolymers2073-43602023-07-011514313310.3390/polym15143133Design, Synthesis, and Comparison of PLA-PEG-PLA and PEG-PLA-PEG Copolymers for Curcumin Delivery to Cancer CellsNeda Rostami0Farzaneh Faridghiasi1Aida Ghebleh2Hadi Noei3Meisam Samadzadeh4Mohammad Mahmoudi Gomari5Alireza Tajiki6Majid Abdouss7Alireza Aminoroaya8Manisha Kumari9Reza Heidari10Vladimir N. Uversky11Bryan R. Smith12Department of Chemistry, Amirkabir University of Technology, Tehran 1591634311, IranDepartment of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran 1449614535, IranSchool of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan 8174673461, IranDepartment of Medical Biology and Genetics, Faculty of Medicine, Istinye University, Istanbul 34010, TurkeyDepartment of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul 34010, TurkeyDepartment of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran 1449614535, IranDepartment of Chemistry, Amirkabir University of Technology, Tehran 1591634311, IranDepartment of Chemistry, Amirkabir University of Technology, Tehran 1591634311, IranDepartment of Biomedical Engineering and Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USADepartment of Biomedical Engineering and Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USAResearch Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran 1411718541, IranDepartment of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USADepartment of Biomedical Engineering and Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USACurcumin (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 (<sup>1</sup>H-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 (IC<sub>50</sub> = 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.https://www.mdpi.com/2073-4360/15/14/3133breast cancercurcumincopolymerdrug deliverynano-informaticsbiomaterials |
| spellingShingle | Neda Rostami Farzaneh Faridghiasi Aida Ghebleh Hadi Noei Meisam Samadzadeh Mohammad Mahmoudi Gomari Alireza Tajiki Majid Abdouss Alireza Aminoroaya Manisha Kumari Reza Heidari Vladimir N. Uversky Bryan R. Smith Design, Synthesis, and Comparison of PLA-PEG-PLA and PEG-PLA-PEG Copolymers for Curcumin Delivery to Cancer Cells Polymers breast cancer curcumin copolymer drug delivery nano-informatics biomaterials |
| title | Design, Synthesis, and Comparison of PLA-PEG-PLA and PEG-PLA-PEG Copolymers for Curcumin Delivery to Cancer Cells |
| title_full | Design, Synthesis, and Comparison of PLA-PEG-PLA and PEG-PLA-PEG Copolymers for Curcumin Delivery to Cancer Cells |
| title_fullStr | Design, Synthesis, and Comparison of PLA-PEG-PLA and PEG-PLA-PEG Copolymers for Curcumin Delivery to Cancer Cells |
| title_full_unstemmed | Design, Synthesis, and Comparison of PLA-PEG-PLA and PEG-PLA-PEG Copolymers for Curcumin Delivery to Cancer Cells |
| title_short | Design, Synthesis, and Comparison of PLA-PEG-PLA and PEG-PLA-PEG Copolymers for Curcumin Delivery to Cancer Cells |
| title_sort | design synthesis and comparison of pla peg pla and peg pla peg copolymers for curcumin delivery to cancer cells |
| topic | breast cancer curcumin copolymer drug delivery nano-informatics biomaterials |
| url | https://www.mdpi.com/2073-4360/15/14/3133 |
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