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Preparation of resveratrol containing poly (lactic-coglycolic acid) nanoparticles and investigation of its cytotoxic effect in C6 glioma cells

Yıl 2022, Cilt: 26 Sayı: 4, 911 - 919, 28.06.2025

Murat Doğan , Fatma Zişan Gürgah

Öz

Cancer is a complex disease involving several important changes in cell morphology that ultimately lead
to tumor formulation. The biological endpoint of cancer is the uncontrolled growth and proliferation of cells. Resveratrol
(RES) is a polyphenolic compound from the stilbene family, which has an important place in the treatment of cancer,
which is used as a pharmaceutical and nutraceutical. Studies have shown that RES has anti-tumor effects in addition to
its antioxidant, antimicrobial and anti-inflammatory effects. RES protects the body against free radicals and inhibits
metabolic events that induce the proliferation of cancer cells. RES is a chemically unstable compound that has problems
crossing the blood-brain barrier. Therefore, it is concluded that carrier systems containing RES should be developed in
order to increase the water dispersibility of resveratrol and to increase its bioavailability when taken orally. In this way,
the RES will be successfully targeted to the tumor site and the undesirable properties of the unstable, heat-sensitive RES
will be improved. For this purpose, drug delivery systems prepared using synthetic polymers such as Polylactic-coglycolic
acid (PLGA) have been developed. PLGA is a biodegradable and biocompatible polymer used in areas related
to human health. In this study, cell culture study of C6 glioma cells obtained from ATCC was performed and for this
purpose, biocompatible nanoparticles of RES with PLGA were prepared. With the preparation of these nanoparticles,
the effects of RES on cell viability and the differences in the anticancer effect on cells were evaluated with the XTT
cytotoxicity study.

Anahtar Kelimeler

Resveratrol PLGA polyvinyl alcohol nanoparticles cytotoxicity

Kaynakça

  • [1] Seyfried TN, Flores RE, Poff AM, D’Agostino DP. Cancer as a metabolic disease: implications for novel therapeutics. Carcinogenesis. 2014; 35(3): 515-527. [CrossRef]
  • [2] Anand P, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, Sung B, Aggarwal BB. Cancer is a preventable disease that requires major lifestyle changes. Pharmaceutical Research. 2008; 25(9): 2097–2116. [CrossRef]
  • [3] Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2018; 68(1): 7–30. [CrossRef]
  • [4] Shewach DS & Kuchta RD. Introduction to cancer chemotherapeutics. Chem Rev. 2009; 109(7): 2859–2861. [CrossRef]
  • [5] Shaili E. Platinum anticancer drugs and photochemotherapeutic agents: recent advances and future developments. Sci Prog. 2014; 97(1): 20–40. [CrossRef]
  • [6] Zupančič Š, Lavrič Z, Kristl J. Stability and solubility of trans-resveratrol are strongly influenced by pH and temperature. Eur J Pharm Biopharm. 2015; 93: 196–204. [CrossRef]
  • [7] Nawaz W, Zhou Z, Deng S, Ma X, Ma X, Li C, Shu X. Therapeutic versatility of resveratrol derivatives. Nutrients. 2017; 9(11): 1188. [CrossRef]
  • [8] Sessa M, Tsao R, Liu R, Ferrari G, Donsi F. Evaluation of the stability and antioxidant activity of nanoencapsulated resveratrol during in vitro digestion. J Agric Food Chem. 2011; 59(23): 12352-12360. [CrossRef]
  • [9] Hao HD & He LR. Mechanisms of cardiovascular protection by resveratrol. J Med Food. 2004; 7(3): 290-298. [CrossRef]
  • [10] Sovak M. Grape extract, resveratrol, and its analogs: A review. J Med Food. 2001; 4(2): 93-105. [CrossRef]
  • [11] Jeandet P, Delaunois B, Aziz A, Donnez D, Vasserot Y, Cordelier S, Courot E. Metabolic Engineering of Yeast and Plants for the Production of the Biologically Active Hydroxystilbene, Resveratrol. 2012. [CrossRef]
  • [12] Athar M, Back JH, Tang X, Kim KH, Kopelovich L, Bickers DR, Kim AL. Resveratrol: a review of preclinical studies for human cancer prevention. Toxicol Appl Pharmacol. 2007; 224(3): 274-283. [CrossRef]
  • [13] Schächinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse longterm outcome of coronary heart disease. Circulation. 2000; 101(16): 1899–1906. [CrossRef]
  • [14] Widlansky ME, Gokce N, Keaney JF, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003; 42(7): 1149–1160. [CrossRef]
  • [15] Hammett R, Shoemake M. In silico design and optimisation of phytoalexin resveratrol polyphenolic analogs as inhibitors of histone acetyltransferase for the management of tumor growth. Medical chemistry. 2018; 8(8): 242- 249. [CrossRef]
  • [16] Augustin MA, Sanguansri L, Lockett T. Nano- and micro-encapsulated systems for enhancing the delivery of resveratrol. ann. Ann NY Acad Sci. 2013; 1290(1): 107–112. [CrossRef]
  • [17] Nazlı AB. Master's Thesis. Investigation of loading and release of resveratrol using in cancer therapy on chitosanalginate composite biogels as drug carrier system. Department of Bioengineering, Institute of Science, Hacettepe University, Ankara, Turkey, 2018.
  • [18] Seeram NP, Kulkarni VV, Padhye S. Sources and Chemistry of Resveratrol. Resveratrol in Health and Disease. 2005;17-32.
  • [19] Uberti F, Morsanuto V, Aprile S, Ghirlanda S, Stoppa I, Cochis A, Grosa G, Rimondini L, Molinari C. Biological effects of combined resveratrol and vitamin D3 on ovarian tissue. J Ovarian Res. 2017; 10(1): 61. [CrossRef]
  • [20] Gambini J, Inglés M, Olaso G, Lopez-Grueso R, Bonet-Costa V, Gimeno-Mallench L, Mas-Bargues C, AbdelazizKM, Gomez-Cabrera MC, Vina J,Borras C. Properties of Resveratrol: In vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxidative Medicine and Cellular Longevity. 2015; 2015: 837042. [CrossRef]
  • [21] Davidov-Pardo G & McClements DJ. Resveratrol encapsulation: Designing delivery systems to overcome solubility, stability and bioavailability issues. Trends in Food Science & Technology. 2014; 38(2): 88-103. [CrossRef]
  • [22] Tinhofer I, Bernhard D, Senfter M, Anether G, Loeffler M, Kroemer G, Kofler R, Csordas A, Greil R. Resveratrol, a tumor-suppressive compound from grapes, induces apoptosis via a novel mitochondrial pathway controlled by Bcl-2. FASEB J. 2001; 15(9): 1613-1615. [CrossRef]
  • [23] Siddiqui IA, Sanna V, Ahmad N, Sechi M, Mukhtar H. Resveratrol nanoformulation for cancer prevention and therapy. Ann NY Acad Sci. 2015; 1348(1): 20-31. [CrossRef]
  • [24] Wahab A, Gao K, Jia C, Zhang F, Tian G, Murtaza G, Chen J. Significance of resveratrol in clinical management of chronic diseases. Molecules. 2017; 22(8): 1329-1334. [CrossRef]
  • [25] Cooper DL, Harirforoosh S. Design and optimization of plga-based diclofenac loaded nanoparticles. PLoS One. 2014; 9(1): e87326. [CrossRef]
  • [26] Panyam J & Labhasetwar V. Biodegradable Nanoparticles for Drug and Gene Delivery to Cells and Tissue. Advanced Drug Delivery Reviews. 2003; 55(3): 329-347. [CrossRef]
  • [27] Singh G, Pai RS. Optimized PLGA nanoparticle platform for orally dosed trans-resveratrol with enhanced bioavailability potential. Expert Opin Drug Deliv. 2014; 11(5): 647–659. [CrossRef]
  • [28] Jain RA. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co glycolide) (PLGA) devices. Biomaterials. 2000; 21(23): 2475-2490. [CrossRef]
  • [29] Jain R, Shah NH, Malick AW, Rhodes CT. Controlled drug delivery by biodegradable poly(ester) devices: different preparative approaches. Drug Dev Ind Pharm. 1998; 24(8): 703-727. [CrossRef]
  • [30] Saxena V, Sadoqi M, Shao J. Polymeric nanoparticulate delivery system for Indocyanine green: biodistribution in healthy mice. Int J Pharm. 2006; 308(1-2): 200-204. [CrossRef]
  • [31] Demir D. Master's Thesis. Formulatıon and ın vıtro evalutıon of nanopartıcles contaınıng docetaxel. Department of Nanotechnology and Nanomedicine, Institute of Science, Hacettepe University, Ankara, Turkey, Ekim, 2013.
  • [32] Fonseca C, Simões S, Gaspar R. Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J Cont Rel. 2002; 83(2): 273-286. [CrossRef]
  • [33] Yurdakul Ö. Master’s Thesis. Investigation of the antioxidant effect of resveratrol in human lung cancer cells (H1299). Department of Bıology, Institute of Science, Akdeniz University, Antalya, Turkey, Haziran 2017.
  • [34] Arus BA, Souza DG, Ballaver B, Souza DO, Goncavesi CA, Quincozes-santos A, Bobermin LD. Resveratrol modulates GSH system in C6 astroglial cells through heme oxygenase 1 pathway. Mol Cell Biochem. 2017; 428(1-2): 67–77. [CrossRef]
  • [35] Jaklenec A, Hinckfuss A, Bilgen B, Ciombor DM, Aaron R, Mathiowitz E. Sequential release of bioactive IGF-I and TGF-beta 1 from PLGA microsphere-based scaffolds. Biomaterials. 2008; 29(10): 1518-1525. [CrossRef]

Yıl 2022, Cilt: 26 Sayı: 4, 911 - 919, 28.06.2025

Murat Doğan , Fatma Zişan Gürgah

Öz

Kaynakça

  • [1] Seyfried TN, Flores RE, Poff AM, D’Agostino DP. Cancer as a metabolic disease: implications for novel therapeutics. Carcinogenesis. 2014; 35(3): 515-527. [CrossRef]
  • [2] Anand P, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, Sung B, Aggarwal BB. Cancer is a preventable disease that requires major lifestyle changes. Pharmaceutical Research. 2008; 25(9): 2097–2116. [CrossRef]
  • [3] Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2018; 68(1): 7–30. [CrossRef]
  • [4] Shewach DS & Kuchta RD. Introduction to cancer chemotherapeutics. Chem Rev. 2009; 109(7): 2859–2861. [CrossRef]
  • [5] Shaili E. Platinum anticancer drugs and photochemotherapeutic agents: recent advances and future developments. Sci Prog. 2014; 97(1): 20–40. [CrossRef]
  • [6] Zupančič Š, Lavrič Z, Kristl J. Stability and solubility of trans-resveratrol are strongly influenced by pH and temperature. Eur J Pharm Biopharm. 2015; 93: 196–204. [CrossRef]
  • [7] Nawaz W, Zhou Z, Deng S, Ma X, Ma X, Li C, Shu X. Therapeutic versatility of resveratrol derivatives. Nutrients. 2017; 9(11): 1188. [CrossRef]
  • [8] Sessa M, Tsao R, Liu R, Ferrari G, Donsi F. Evaluation of the stability and antioxidant activity of nanoencapsulated resveratrol during in vitro digestion. J Agric Food Chem. 2011; 59(23): 12352-12360. [CrossRef]
  • [9] Hao HD & He LR. Mechanisms of cardiovascular protection by resveratrol. J Med Food. 2004; 7(3): 290-298. [CrossRef]
  • [10] Sovak M. Grape extract, resveratrol, and its analogs: A review. J Med Food. 2001; 4(2): 93-105. [CrossRef]
  • [11] Jeandet P, Delaunois B, Aziz A, Donnez D, Vasserot Y, Cordelier S, Courot E. Metabolic Engineering of Yeast and Plants for the Production of the Biologically Active Hydroxystilbene, Resveratrol. 2012. [CrossRef]
  • [12] Athar M, Back JH, Tang X, Kim KH, Kopelovich L, Bickers DR, Kim AL. Resveratrol: a review of preclinical studies for human cancer prevention. Toxicol Appl Pharmacol. 2007; 224(3): 274-283. [CrossRef]
  • [13] Schächinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse longterm outcome of coronary heart disease. Circulation. 2000; 101(16): 1899–1906. [CrossRef]
  • [14] Widlansky ME, Gokce N, Keaney JF, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003; 42(7): 1149–1160. [CrossRef]
  • [15] Hammett R, Shoemake M. In silico design and optimisation of phytoalexin resveratrol polyphenolic analogs as inhibitors of histone acetyltransferase for the management of tumor growth. Medical chemistry. 2018; 8(8): 242- 249. [CrossRef]
  • [16] Augustin MA, Sanguansri L, Lockett T. Nano- and micro-encapsulated systems for enhancing the delivery of resveratrol. ann. Ann NY Acad Sci. 2013; 1290(1): 107–112. [CrossRef]
  • [17] Nazlı AB. Master's Thesis. Investigation of loading and release of resveratrol using in cancer therapy on chitosanalginate composite biogels as drug carrier system. Department of Bioengineering, Institute of Science, Hacettepe University, Ankara, Turkey, 2018.
  • [18] Seeram NP, Kulkarni VV, Padhye S. Sources and Chemistry of Resveratrol. Resveratrol in Health and Disease. 2005;17-32.
  • [19] Uberti F, Morsanuto V, Aprile S, Ghirlanda S, Stoppa I, Cochis A, Grosa G, Rimondini L, Molinari C. Biological effects of combined resveratrol and vitamin D3 on ovarian tissue. J Ovarian Res. 2017; 10(1): 61. [CrossRef]
  • [20] Gambini J, Inglés M, Olaso G, Lopez-Grueso R, Bonet-Costa V, Gimeno-Mallench L, Mas-Bargues C, AbdelazizKM, Gomez-Cabrera MC, Vina J,Borras C. Properties of Resveratrol: In vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxidative Medicine and Cellular Longevity. 2015; 2015: 837042. [CrossRef]
  • [21] Davidov-Pardo G & McClements DJ. Resveratrol encapsulation: Designing delivery systems to overcome solubility, stability and bioavailability issues. Trends in Food Science & Technology. 2014; 38(2): 88-103. [CrossRef]
  • [22] Tinhofer I, Bernhard D, Senfter M, Anether G, Loeffler M, Kroemer G, Kofler R, Csordas A, Greil R. Resveratrol, a tumor-suppressive compound from grapes, induces apoptosis via a novel mitochondrial pathway controlled by Bcl-2. FASEB J. 2001; 15(9): 1613-1615. [CrossRef]
  • [23] Siddiqui IA, Sanna V, Ahmad N, Sechi M, Mukhtar H. Resveratrol nanoformulation for cancer prevention and therapy. Ann NY Acad Sci. 2015; 1348(1): 20-31. [CrossRef]
  • [24] Wahab A, Gao K, Jia C, Zhang F, Tian G, Murtaza G, Chen J. Significance of resveratrol in clinical management of chronic diseases. Molecules. 2017; 22(8): 1329-1334. [CrossRef]
  • [25] Cooper DL, Harirforoosh S. Design and optimization of plga-based diclofenac loaded nanoparticles. PLoS One. 2014; 9(1): e87326. [CrossRef]
  • [26] Panyam J & Labhasetwar V. Biodegradable Nanoparticles for Drug and Gene Delivery to Cells and Tissue. Advanced Drug Delivery Reviews. 2003; 55(3): 329-347. [CrossRef]
  • [27] Singh G, Pai RS. Optimized PLGA nanoparticle platform for orally dosed trans-resveratrol with enhanced bioavailability potential. Expert Opin Drug Deliv. 2014; 11(5): 647–659. [CrossRef]
  • [28] Jain RA. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co glycolide) (PLGA) devices. Biomaterials. 2000; 21(23): 2475-2490. [CrossRef]
  • [29] Jain R, Shah NH, Malick AW, Rhodes CT. Controlled drug delivery by biodegradable poly(ester) devices: different preparative approaches. Drug Dev Ind Pharm. 1998; 24(8): 703-727. [CrossRef]
  • [30] Saxena V, Sadoqi M, Shao J. Polymeric nanoparticulate delivery system for Indocyanine green: biodistribution in healthy mice. Int J Pharm. 2006; 308(1-2): 200-204. [CrossRef]
  • [31] Demir D. Master's Thesis. Formulatıon and ın vıtro evalutıon of nanopartıcles contaınıng docetaxel. Department of Nanotechnology and Nanomedicine, Institute of Science, Hacettepe University, Ankara, Turkey, Ekim, 2013.
  • [32] Fonseca C, Simões S, Gaspar R. Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J Cont Rel. 2002; 83(2): 273-286. [CrossRef]
  • [33] Yurdakul Ö. Master’s Thesis. Investigation of the antioxidant effect of resveratrol in human lung cancer cells (H1299). Department of Bıology, Institute of Science, Akdeniz University, Antalya, Turkey, Haziran 2017.
  • [34] Arus BA, Souza DG, Ballaver B, Souza DO, Goncavesi CA, Quincozes-santos A, Bobermin LD. Resveratrol modulates GSH system in C6 astroglial cells through heme oxygenase 1 pathway. Mol Cell Biochem. 2017; 428(1-2): 67–77. [CrossRef]
  • [35] Jaklenec A, Hinckfuss A, Bilgen B, Ciombor DM, Aaron R, Mathiowitz E. Sequential release of bioactive IGF-I and TGF-beta 1 from PLGA microsphere-based scaffolds. Biomaterials. 2008; 29(10): 1518-1525. [CrossRef]
Toplam 35 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Farmasotik Biyoteknoloji
Bölüm Articles
Yazarlar

Murat Doğan 0000-0003-2794-0177

Fatma Zişan Gürgah 0000-0001-8712-8602

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2022 Cilt: 26 Sayı: 4

Kaynak Göster

APA Doğan, M., & Gürgah, F. Z. (2025). Preparation of resveratrol containing poly (lactic-coglycolic acid) nanoparticles and investigation of its cytotoxic effect in C6 glioma cells. Journal of Research in Pharmacy, 26(4), 911-919.
AMA Doğan M, Gürgah FZ. Preparation of resveratrol containing poly (lactic-coglycolic acid) nanoparticles and investigation of its cytotoxic effect in C6 glioma cells. J. Res. Pharm. Haziran 2025;26(4):911-919.
Chicago Doğan, Murat, ve Fatma Zişan Gürgah. “Preparation of Resveratrol Containing Poly (lactic-Coglycolic Acid) Nanoparticles and Investigation of Its Cytotoxic Effect in C6 Glioma Cells”. Journal of Research in Pharmacy 26, sy. 4 (Haziran 2025): 911-19.
EndNote Doğan M, Gürgah FZ (01 Haziran 2025) Preparation of resveratrol containing poly (lactic-coglycolic acid) nanoparticles and investigation of its cytotoxic effect in C6 glioma cells. Journal of Research in Pharmacy 26 4 911–919.
IEEE M. Doğan ve F. Z. Gürgah, “Preparation of resveratrol containing poly (lactic-coglycolic acid) nanoparticles and investigation of its cytotoxic effect in C6 glioma cells”, J. Res. Pharm., c. 26, sy. 4, ss. 911–919, 2025.
ISNAD Doğan, Murat - Gürgah, Fatma Zişan. “Preparation of Resveratrol Containing Poly (lactic-Coglycolic Acid) Nanoparticles and Investigation of Its Cytotoxic Effect in C6 Glioma Cells”. Journal of Research in Pharmacy 26/4 (Haziran 2025), 911-919.
JAMA Doğan M, Gürgah FZ. Preparation of resveratrol containing poly (lactic-coglycolic acid) nanoparticles and investigation of its cytotoxic effect in C6 glioma cells. J. Res. Pharm. 2025;26:911–919.
MLA Doğan, Murat ve Fatma Zişan Gürgah. “Preparation of Resveratrol Containing Poly (lactic-Coglycolic Acid) Nanoparticles and Investigation of Its Cytotoxic Effect in C6 Glioma Cells”. Journal of Research in Pharmacy, c. 26, sy. 4, 2025, ss. 911-9.
Vancouver Doğan M, Gürgah FZ. Preparation of resveratrol containing poly (lactic-coglycolic acid) nanoparticles and investigation of its cytotoxic effect in C6 glioma cells. J. Res. Pharm. 2025;26(4):911-9.