Resveratrol-Loaded Polymeric Nanoparticles: The Effects of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) on Physicochemical and Biological Properties against Breast Cancer In Vitro and In Vivo
Resveratrol (RSV), a phytoalexin from grapes and peanuts, has been reported to exhibit antiproliferative effects on various cancer cell lines. In breast cancer, RSV has been demonstrated to exert an antiproliferative effect on both hormone-dependent and hormone-independent breast cancer cell lines....
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/10/2802 |
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| author | Paulo George Cavalcante de Freitas Bruno Rodrigues Arruda Maria Gabriela Araújo Mendes João Vito Barroso de Freitas Mateus Edson da Silva Tiago Lima Sampaio Raquel Petrilli Josimar O. Eloy |
| author_facet | Paulo George Cavalcante de Freitas Bruno Rodrigues Arruda Maria Gabriela Araújo Mendes João Vito Barroso de Freitas Mateus Edson da Silva Tiago Lima Sampaio Raquel Petrilli Josimar O. Eloy |
| author_sort | Paulo George Cavalcante de Freitas |
| collection | DOAJ |
| description | Resveratrol (RSV), a phytoalexin from grapes and peanuts, has been reported to exhibit antiproliferative effects on various cancer cell lines. In breast cancer, RSV has been demonstrated to exert an antiproliferative effect on both hormone-dependent and hormone-independent breast cancer cell lines. However, RSV is a lipophilic drug, and its therapeutic effect could be improved through nanoencapsulation. Functionalizing polymeric nanoparticles based on polycaprolactone (PCL) with polyethylene glycol 1000 tocopheryl succinate (TPGS) has been reported to prolong drug circulation and reduce drug resistance. However, the effect of TPGS on the physicochemical properties and biological effects of breast cancer cells remains unclear. Therefore, this study aimed to develop RSV-loaded PCL nanoparticles using nanoprecipitation and investigate the effect of TPGS on the nanoparticles’ physicochemical characteristics (particle size, zeta potential, encapsulation efficiency, morphology, and release rate) and biological effects on the 4T1 breast cancer cell line (cytotoxicity and cell uptake), in vitro and in vivo. The optimized nanoparticles without TPGS had a size of 138.1 ± 1.8 nm, a polydispersity index (PDI) of 0.182 ± 0.01, a zeta potential of −2.42 ± 0.56 mV, and an encapsulation efficiency of 98.2 ± 0.87%, while nanoparticles with TPGS had a size of 127.5 ± 3.11 nm, PDI of 0.186 ± 0.01, zeta potential of −2.91 ± 0.90 mV, and an encapsulation efficiency of 98.40 ± 0.004%. Scanning electron microscopy revealed spherical nanoparticles with low aggregation tendency. Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR) identified the constituents of the nanoparticles and the presence of drug encapsulation in an amorphous state. In vitro release studies showed that both formulations followed the same dissolution profiles, with no statistical differences. In cytotoxicity tests, IC<sub>50</sub> values of 0.12 µM, 0.73 µM, and 4.06 µM were found for the formulation without TPGS, with TPGS, and pure drug, respectively, indicating the potentiation of the cytotoxic effect of resveratrol when encapsulated. Flow cytometry and confocal microscopy tests indicated excellent cellular uptake dependent on the concentration of nanoparticles, with a significant difference between the two formulations, suggesting that TPGS may pose a problem in the endocytosis of nanoparticles. The in vivo study evaluating the antitumor activity of the nanoparticles confirmed the data obtained in the in vitro tests, demonstrating that the nanoparticle without TPGS significantly reduced tumor volume, tumor mass, maintained body weight, and improved survival in mice. Moreover, the biochemical evaluation evidenced possible hepatotoxicity for formulation with TPGS. |
| first_indexed | 2024-03-11T03:51:25Z |
| format | Article |
| id | doaj.art-1d66f1023d084bbb963f18187949a034 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T03:51:25Z |
| publishDate | 2023-05-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1d66f1023d084bbb963f18187949a0342023-11-18T00:49:12ZengMDPI AGCancers2072-66942023-05-011510280210.3390/cancers15102802Resveratrol-Loaded Polymeric Nanoparticles: The Effects of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) on Physicochemical and Biological Properties against Breast Cancer In Vitro and In VivoPaulo George Cavalcante de Freitas0Bruno Rodrigues Arruda1Maria Gabriela Araújo Mendes2João Vito Barroso de Freitas3Mateus Edson da Silva4Tiago Lima Sampaio5Raquel Petrilli6Josimar O. Eloy7Department of Pharmacy, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Fortaleza 60430-160, CE, BrazilDepartment of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza 60430-160, CE, BrazilDepartment of Pharmacy, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Fortaleza 60430-160, CE, BrazilDepartment of Pharmacy, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Fortaleza 60430-160, CE, BrazilDepartment of Pharmacy, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Fortaleza 60430-160, CE, BrazilDepartment of Pharmacy, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Fortaleza 60430-160, CE, BrazilInstitute of Health Sciences, University of International Integration of the Afro-Brazilian Lusophony—UNILAB, Redenção 62790-000, CE, BrazilDepartment of Pharmacy, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Fortaleza 60430-160, CE, BrazilResveratrol (RSV), a phytoalexin from grapes and peanuts, has been reported to exhibit antiproliferative effects on various cancer cell lines. In breast cancer, RSV has been demonstrated to exert an antiproliferative effect on both hormone-dependent and hormone-independent breast cancer cell lines. However, RSV is a lipophilic drug, and its therapeutic effect could be improved through nanoencapsulation. Functionalizing polymeric nanoparticles based on polycaprolactone (PCL) with polyethylene glycol 1000 tocopheryl succinate (TPGS) has been reported to prolong drug circulation and reduce drug resistance. However, the effect of TPGS on the physicochemical properties and biological effects of breast cancer cells remains unclear. Therefore, this study aimed to develop RSV-loaded PCL nanoparticles using nanoprecipitation and investigate the effect of TPGS on the nanoparticles’ physicochemical characteristics (particle size, zeta potential, encapsulation efficiency, morphology, and release rate) and biological effects on the 4T1 breast cancer cell line (cytotoxicity and cell uptake), in vitro and in vivo. The optimized nanoparticles without TPGS had a size of 138.1 ± 1.8 nm, a polydispersity index (PDI) of 0.182 ± 0.01, a zeta potential of −2.42 ± 0.56 mV, and an encapsulation efficiency of 98.2 ± 0.87%, while nanoparticles with TPGS had a size of 127.5 ± 3.11 nm, PDI of 0.186 ± 0.01, zeta potential of −2.91 ± 0.90 mV, and an encapsulation efficiency of 98.40 ± 0.004%. Scanning electron microscopy revealed spherical nanoparticles with low aggregation tendency. Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR) identified the constituents of the nanoparticles and the presence of drug encapsulation in an amorphous state. In vitro release studies showed that both formulations followed the same dissolution profiles, with no statistical differences. In cytotoxicity tests, IC<sub>50</sub> values of 0.12 µM, 0.73 µM, and 4.06 µM were found for the formulation without TPGS, with TPGS, and pure drug, respectively, indicating the potentiation of the cytotoxic effect of resveratrol when encapsulated. Flow cytometry and confocal microscopy tests indicated excellent cellular uptake dependent on the concentration of nanoparticles, with a significant difference between the two formulations, suggesting that TPGS may pose a problem in the endocytosis of nanoparticles. The in vivo study evaluating the antitumor activity of the nanoparticles confirmed the data obtained in the in vitro tests, demonstrating that the nanoparticle without TPGS significantly reduced tumor volume, tumor mass, maintained body weight, and improved survival in mice. Moreover, the biochemical evaluation evidenced possible hepatotoxicity for formulation with TPGS.https://www.mdpi.com/2072-6694/15/10/2802resveratrolTPGSnanoparticlepoly-ε-caprolactonebreast cancer |
| spellingShingle | Paulo George Cavalcante de Freitas Bruno Rodrigues Arruda Maria Gabriela Araújo Mendes João Vito Barroso de Freitas Mateus Edson da Silva Tiago Lima Sampaio Raquel Petrilli Josimar O. Eloy Resveratrol-Loaded Polymeric Nanoparticles: The Effects of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) on Physicochemical and Biological Properties against Breast Cancer In Vitro and In Vivo Cancers resveratrol TPGS nanoparticle poly-ε-caprolactone breast cancer |
| title | Resveratrol-Loaded Polymeric Nanoparticles: The Effects of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) on Physicochemical and Biological Properties against Breast Cancer In Vitro and In Vivo |
| title_full | Resveratrol-Loaded Polymeric Nanoparticles: The Effects of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) on Physicochemical and Biological Properties against Breast Cancer In Vitro and In Vivo |
| title_fullStr | Resveratrol-Loaded Polymeric Nanoparticles: The Effects of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) on Physicochemical and Biological Properties against Breast Cancer In Vitro and In Vivo |
| title_full_unstemmed | Resveratrol-Loaded Polymeric Nanoparticles: The Effects of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) on Physicochemical and Biological Properties against Breast Cancer In Vitro and In Vivo |
| title_short | Resveratrol-Loaded Polymeric Nanoparticles: The Effects of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) on Physicochemical and Biological Properties against Breast Cancer In Vitro and In Vivo |
| title_sort | resveratrol loaded polymeric nanoparticles the effects of d α tocopheryl polyethylene glycol 1000 succinate tpgs on physicochemical and biological properties against breast cancer in vitro and in vivo |
| topic | resveratrol TPGS nanoparticle poly-ε-caprolactone breast cancer |
| url | https://www.mdpi.com/2072-6694/15/10/2802 |
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