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      Polymeric micelles containing resveratrol: development, characterization, cytotoxicity on tumor cells and antimicrobial activity

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          Abstract

          Antimicrobial and antitumor activities of resveratrol, a compound found mainly in grapes, have already been demonstrated. However, its low bioavailability is a limiting factor for therapeutic application. Polymeric micelles can be an approach to solve this problem since they can encapsulate hydrophobic substances. We developed and characterized micellar formulations containing resveratrol and evaluated their cytotoxic and antimicrobial effects. The formulations were prepared by the cold dispersion method with different concentrations of F127 (5 or 10% w/w) and resveratrol (500 or 5000 µM). The formulations were characterized according to size, polydispersity index, pH, encapsulation rate and in vitro release. Cytotoxic effect was evaluated on a bladder cancer cell line and antimicrobial effect was evaluated on E. coli, S. aureus and C. albicans. One of the formulations (10% w/w of F127 and 5000 µM of resveratrol) was a monodispersed solution with high encapsulation rate, thus it was chosen for the cytotoxicity and antimicrobial assays. MS- 10+RES-3 was able to preserve the antimicrobial and cytotoxic activity of resveratrol. This is the first study that evaluated antimicrobial potential and cytotoxicity of micelles containing resveratrol on bladder cancer cells and the results showed that micellar nanostructures could ensure the maintenance of the biological activity of resveratrol.

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          Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients.

          Resveratrol is a phytochemical with chemopreventive activity in preclinical rodent models of colorectal carcinogenesis. Antiproliferation is one of the many chemopreventive modes of action it has been shown to engage in. Concentrations of resveratrol, which can be achieved in human tissues after p.o. administration, have not yet been defined. The purpose of this study was to measure concentrations of resveratrol and its metabolites in the colorectal tissue of humans who ingested resveratrol. Twenty patients with histologically confirmed colorectal cancer consumed eight daily doses of resveratrol at 0.5 or 1.0 g before surgical resection. Resveratrol was found to be well tolerated. Normal and malignant biopsy tissue samples were obtained before dosing. Parent compound plus its metabolites resveratrol-3-O-glucuronide, resveratrol-4'-O-glucuronide, resveratrol-3-O-sulfate, resveratrol-4'-O-sulfate, resveratrol sulfate glucuronide, and resveratrol disulfate were identified by high-performance liquid chromatography (HPLC) with UV or mass spectrometric detection in colorectal resection tissue. Quantitation was achieved by HPLC/UV. Cell proliferation, as reflected by Ki-67 staining, was compared in preintervention and postintervention tissue samples. Resveratrol and resveratrol-3-O-glucuronide were recovered from tissues at maximal mean concentrations of 674 and 86.0 nmol/g, respectively. Levels of resveratrol and its metabolites were consistently higher in tissues originating in the right side of the colon compared with the left. Consumption of resveratrol reduced tumor cell proliferation by 5% (P = 0.05). The results suggest that daily p.o. doses of resveratrol at 0.5 or 1.0 g produce levels in the human gastrointestinal tract of an order of magnitude sufficient to elicit anticarcinogenic effects. Resveratrol merits further clinical evaluation as a potential colorectal cancer chemopreventive agent. © 2010 AACR.
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            The outer membrane is an essential load-bearing element in Gram-negative bacteria

            Gram-negative bacteria possess a complex cell envelope consisting of a plasma membrane, a peptidoglycan cell wall, and an outer membrane. The envelope is a selective chemical barrier 1 that defines cell shape 2 and allows the cell to sustain large mechanical loads such as turgor pressure 3 . It is widely believed that the covalently cross-linked cell wall grants the envelope its mechanical properties 4,5 . Here, we demonstrate that the stiffness and strength of Escherichia coli cells are largely due to the outer membrane. Compromising the outer membrane, chemically or genetically, greatly increased deformation of the cell envelope in response to stretching, bending, and indentation forces, and induced elevated levels of cell lysis upon mechanical perturbation and L-form proliferation. Both lipopolysaccharides and proteins contributed to outer membrane stiffness. These findings overturn the prevailing dogma that the cell wall is the dominant mechanical element within Gram-negative bacteria, instead demonstrating that the outer membrane can be more stiff than the cell wall and that mechanical loads are often balanced between these structures.
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              Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery.

              Pluronic block copolymers are found to be an efficient drug delivery system with multiple effects. The incorporation of drugs into the core of the micelles formed by Pluronic results in increased solubility, metabolic stability and circulation time for the drug. The interactions of the Pluronic unimers with multidrug-resistant cancer cells result in sensitization of these cells with respect to various anticancer agents. Furthermore, the single molecular chains of copolymer, unimers, inhibit drug efflux transporters in both the blood-brain barrier and in the small intestine, which provides for the enhanced transport of select drugs to the brain and increases oral bioavailability. These and other applications of Pluronic block copolymers in various drug delivery and gene delivery systems are considered.
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                Author and article information

                Journal
                bjps
                Brazilian Journal of Pharmaceutical Sciences
                Braz. J. Pharm. Sci.
                Universidade de São Paulo, Faculdade de Ciências Farmacêuticas (São Paulo, SP, Brazil )
                2175-9790
                2020
                : 56
                : e18411
                Affiliations
                [2] Ouro Preto Minas Gerais orgnameUniversidade Federal de Ouro Preto orgdiv1Departamento de Farmácia orgdiv2Laboratório de Fitotecnologia Brazil
                [5] Ouro Preto Minas Gerais orgnameUniversidade Federal de Ouro Preto orgdiv1Departamento de Física orgdiv2Laboratório de Fotofísica Molecular Brazil
                [3] Ouro Preto Minas Gerais orgnameUniversidade Federal de Ouro Preto orgdiv1Departamento de Análises Clínicas orgdiv2Laboratório de Microbiologia Brazil
                [1] Ouro Preto Minas Gerais orgnameUniversidade Federal de Ouro Preto orgdiv1Departamento de Análises Clínicas orgdiv2Laboratório de Pesquisas Clínicas Brazil
                [4] Pelotas Rio Grande do Sul orgnameUniversidade Federal de Pelotas orgdiv1Centro de Ciências Químicas, Farmacêuticas e de Alimentos orgdiv2Laboratório de Tecnologia Farmacêutica Brazil
                Article
                S1984-82502020000100567 S1984-8250(20)05600000567
                10.1590/s2175-97902019000418401
                4acd9d3d-d3af-48d7-b4b3-2e872cbb6b3d

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 05 June 2018
                : 08 January 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 62, Pages: 0
                Product

                SciELO Brazil

                Categories
                Articles

                Cytotoxic activity,F127®,Resveratrol,Antimicrobial activity,Polymeric micelles

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