Poli(Rutin) Micro/nanogels for Biomedical Applications

Flavonoids are natural phenolic compounds that are active molecules commonly found in woody and herbaceous plants and used in natural defense mechanisms of plants against harmful microorganisms. In this research, rutin (RUT) molecule which is a natural flavonoid was bounded with epoxy groups of poly(ethylene glycol) diglycidyl ether crosslinker by using micro emulsion crosslinking technique to synthesize of poly(rutin) (p(RUT)) micro/nanogels. These p(RUT) micro/nanogels showed spherical morphologic structure with 0.3 nm-2 µm dry size range due to scanning electron microscope image. Furthermore, p(RUT) micro/nanogels was found to be in injectable size range with 548±8.9 nm average size distribution in aqueous solution depends on the dynamic light scattering (DLS) measurement. In addition, the zeta potential measurements performed at different pH conditions and potentiometric titration of the prepared p(RUT) micro/nanogels was also determined and the isoelectronic point and pKa values of these micro/nanogels was estimated as pH 2.85 and 2.16, respectively. The effects of RUT and p(RUT) micro/nanogels on α-glycosidase (AG) (EC 3.2.1.20) enzyme activity were investigated and it was found that RUT and p(RUT) micro/nanogels stimulate this enzyme. Moreover, fibrinogen interaction results showed that p(RUT) micro/nanogels were more compatible than RUT for vascular system with less interaction ability of fibrinogen of p(RUT) micro/nanogels. In addition, p(RUT) micro/nanogels observed highest antioxidant scavenging ability with 251.3±20.2 gallic acid equivalency total flavonoid content (TFC) at 250 µg/mL and reduced of 1.75±0.27 µmol Fe (III) even for 5 µg p(RUT) microgel/nanogels. Furthermore, no Fe (II) chelating activity was obtained for RUT monomer, but p(RUT) micro/nanogels showed significant Fe (II) chelating activity as 43.11±17.4 %.

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  • 1. Zhang Z, Yang L, Hou J, Tian S, Liu Y. Molecular mechanisms underlying the anticancer activities of licorice flavonoids. Journal of Ethnopharmacology 267 (2021) 113635.
  • 2. Pratheeshkumar P, Budhraja A, Son Y-O, Wang X, Zhang Z, Ding S, et al. Quercetin inhibits angiogenesis mediated human prostate tumor growth by targeting VEGFR- 2 regulated AKT/mTOR/P70S6K signaling pathways. Gautam S, editor. PLoS ONE 2012 Oct 18;7(10):e47516.
  • 3. Machado DG, Bettio LEB, Cunha MP, Santos ARS, Pizzolatti MG, Brighente IMC, et al. Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. in mice: Evidence for the involvement of the serotonergic and noradrenergic systems. European Journal of Pharmacology 587 (2008) 163–168.
  • 4. Gao L, Schäfer C, O’Reardon K, Gorgus E, Schulte-Hubbert R, Schrenk D. The mutagenic potency of onion juice vs. its contents of quercetin and rutin. Food and Chemical Toxicology148 (2021) 111923.
  • 5. Ganeshpurkar A, Saluja AK. The Pharmacological Potential of Rutin. Saudi Pharmaceutical Journal 25 (2017) 149–164.
  • 6. Montes A, Wehner L, Pereyra C, Martínez de la Ossa EJ. Precipitation of submicron particles of rutin using supercritical antisolvent process. The Journal of Supercritical Fluids 118 (2016) 1–10.
  • 7. Ekaette I, Saldaña MDA. Ultrasound processing of rutin in food-grade solvents: Derivative compounds, antioxidant activities and optical rotation. Food Chemistry 344 (2021) 128629.
  • 8. Baldissera MD, Souza CF, Zanella R, Prestes OD, Meinhart AD, Da Silva AS, et al. Behavioral impairment and neurotoxic responses of silver catfish Rhamdia quelen exposed to organophosphate pesticide trichlorfon: Protective effects of diet containing rutin. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 239( 2021) 108871.
  • 9. Sahiner N, Sagbas S, Sahiner M, Aktas N. Degradable Natural Phenolic Based Particles with Micro- and Nano-size Range. Recent Patents on Materials Science 11 (2018) 33–40.
  • 10. Oboh G, Adebayo AA, Ademosun AO, Olowokere OG. Rutin restores neurobehavioral deficits via alterations in cadmium bioavailability in the brain of rats exposed to cadmium. NeuroToxicology 77 (2020) 12–19.
  • 11. Habtemariam S. Rutin as a Natural Therapy for Alzheimer’s Disease: Insights into its Mechanisms of Action. Current Medicinal Chemistry 23(2016 ) 860–873.
  • 12. Kirschweng B, Tilinger DM, Hégely B, Samu G, Tátraaljai D, Földes E, et al. Melt stabilization of PE with natural antioxidants: Comparison of rutin and quercetin. European Polymer Journal 103 (2018) 228–237.
  • 13. Kook D, Wolf AH, Yu AL, Neubauer AS, Priglinger SG, Kampik A, et al. The protective effect of quercetin against oxidative stress in the human RPE in vitro. Investigative Opthalmology & Visual Science 49 (2008) 1712-1720.
  • 14. Anderson CQ, Wechter E, Siegmund LA. Glycogen storage disease type l: don’t miss the signs. The Journal for Nurse Practitioners 16 (2020) 442–446.
  • 15. Marusic T, Zerjav Tansek M, Sirca Campa A, Mezek A, Berden P, Battelino T, et al. Normalization of obstructive cardiomyopathy and improvement of hepatopathy on ketogenic diet in patient with glycogen storage disease (GSD) type IIIa. Molecular Genetics and Metabolism Reports 24 (2020) 100628.
  • 16. Tagera JM, Pj R, Elferink O, Reuser A, Kroosb M, Ginselb LA, et al. a-Glucosidase Deficiency ( Pompe ’ s Disease ) 285 (1987) 280–285.
  • 17. van Kooten HA, Roelen CHA, Brusse E, van der Beek NAME, Michels M, van der Ploeg AT, et al. Cardiovascular disease in non-classic Pompe disease: A systematic review. Neuromuscular Disorders 31 (2021) 79–90.
  • 18 Sahiner N. One step poly(rutin) particle preparation as biocolloid and its characterization. Materials Science and Engineering: C 44 (2014) 9–16.
  • 19. Sahiner M, Sahiner N, Sagbas S, Fullerton ML, Blake DA. Fabrication of Biodegradable Poly(naringin) Particles with Antioxidant Activity and Low Toxicity. ACS Omega 3 (2018) 17359–17367.
  • 20. Deng L, Qi Y, Liu Z, Xi Y, Xue W. Effect of tannic acid on blood components and functions. Colloids and Surfaces B: Biointerfaces 184 (2019) 110505.
  • 21. Li Y, Ma D, Sun D, Wang C, Zhang J, Xie Y, et al. Total phenolic, flavonoid content, and antioxidant activity of flour, noodles, and steamed bread made from different colored wheat grains by three milling methods. The Crop Journal 3(2015) 328–334.
  • 22. Firuzi O, Lacanna A, Petrucci R, Marrosu G, Saso L. Evaluation of the antioxidant activity of flavonoids by “ferric reducing antioxidant power” assay and cyclic voltammetry. Biochimica et Biophysica Acta (BBA) - General Subjects 1721 (2005)174–184.
  • 23. Tadapaneni RK, Banaszewski K, Patazca E, Edirisinghe I, Cappozzo J, Jackson L, et al. Effect of High-Pressure Processing and Milk on the Anthocyanin Composition and Antioxidant Capacity of Strawberry-Based Beverages. Journal of Agricultural and Food Chemistry 60 (2012) 5795–5802.
  • 24. Suner SS, Sahiner M, Ayyala RS, Bhethanabotla VR, Sahiner N. Nitrogen-Doped Arginine Carbon Dots and Its Metal Nanoparticle Composites as Antibacterial Agent. C—Journal of Carbon Research 6 (2020) 58.
  • 25. Alam MA, Zaidul ISM, Ghafoor K, Sahena F, Hakim MA, Rafii MY, et al. In vitro antioxidant and, α-glucosidase inhibitory activities and comprehensive metabolite profiling of methanol extract and its fractions from Clinacanthus nutans. BMC Complementary and Alternative Medicine 17 (2017) 181.
  • 26. Dubey S, Ganeshpurkar A, Ganeshpurkar A, Bansal D, Dubey N. Glycolytic enzyme inhibitory and antiglycation potential of rutin. Future Journal of Pharmaceutical Sciences 3 (2017) 158–162.
  • 27. Tomasik P, Horton D. Enzymatic conversions of starch. In: Advances in Carbohydrate Chemistry and Biochemistry 1st ed. Elsevier Inc.; 2012 59–436.
  • 28. Zhou T, Ma Y, Kong X, Hider RC. Design of iron chelators with therapeutic application. Dalton Transactions 41 (2012) 6371-6389.