Antioxidant Activity and Hemocompatibility Study of Quercetin Loaded Plga Nanoparticles

Document Type : Research article


1 Bioengineering Department, Chemical and Metallurgical Faculty, Yıldız Technical University, Istanbul,Turkey.

2 Bioengineering Department, Chemical and Metallurgical Engineering Faculty, Yildiz Technical University, Istanbul, Turkey.

3 Bioengineering Department , Faculty of Chemical and Metallurgy, Yildiz Technical University, Istanbul,Turkey.

4 Molecular Biology and Genetics Department, Science and Letters Faculty, Yıldız Technical University, Istanbul, Turkey.

5 Medical Biology Department, Medicine Faculty, Altinbas University, Bakirkoy, Istanbul, Turkey.

6 Bioengineering Department, Engineering and Architecture Faculty, Konya Food and Agriculture University, Konya, Turkey.


Quercetin (QU) is an important flavonoid compound presenting lots of biological activities, but its application has been limited due to its low aqueous solubility and instability. In this study, in which conducted to improve these properties of the quercetin, quercetin-encapsulated PLGA nanoparticles were prepared, characterized and evaluated for antioxidant and hemolytic activity. Nanoparticles were produced by single emulsion solvent evaporation method. Four different process parameters initial QU amount, PVA concentration, PVA volume, and initial PLGA amount, were investigated to obtain the nanoparticles which have minimum particle size and maximum entrapment efficiency. Synthesized nanoparticles were evaluated for particle size, entrapment efficiency, and reaction yield. Additionally, antioxidant properties and in vitro hemolytic activity of quercetin loaded nanoparticles with different particle size were also evaluated for the first time in the literature. The antioxidant activity results showed that, nanoparticles have different antioxidant activity, depending on the amount of quercetin release from nanoparticles at different particle sizes. The hemolytic activity results show that all nanoparticles exhibited favorable compatibility to red blood cells and no significant hemolytic effect was observed.

Graphical Abstract

Antioxidant Activity and Hemocompatibility Study of Quercetin Loaded Plga Nanoparticles


Main Subjects

(1) Nam J-S, Sharma AR, Nguyen LT, Chakraborty C,Sharma G and Lee S-S. Application of bioactivequercetin in oncotherapy: from nutrition tonanomedicine. Molecules (2016) 21: 108.
(2) Nathiya S, Durga M and Devasena T. Preparation,Physico-Chemical Characterization andBiocompatibility Evaluation of Quercetin LoadedChitosan Nanoparticles and Its Novel Potential to 434 Antioxidant and Hemolytic Activity of NanoparticlesAmeliorate Monocrotophos Induced Toxicity. Dig.J. Nanomater. Bios. (2014) 9: 1603-13.
(3) Wu T-H, Yen F-L, Lin L-T, Tsai T-R, Lin C-Cand Cham T-M. Preparation, physicochemicalcharacterization, and antioxidant effects of quercetin nanoparticles. Int. J. Pharm. (2008) 346: 160-8.
(4) Molina MF, Sanchez-Reus I, Iglesias I and Benedi J. Quercetin, a flavonoid antioxidant, prevents and protects against ethanol-induced oxidative stress in mouse liver. Biol. Pharm. Bull. (2003) 26: 1398-402.
(5) Coşkun Ö, Kanter M, Armutçu F, Çetin K,Kaybolmaz B and Yazgan Ö. Protective effectsof quercetin, a flavonoid antioxidant, in absolute ethanol-induced acut gastric ulcer. Eur. J. Gen. Med.(2004) 3: 37–42
(6) Arasoglu T, Derman S, Mansuroglu B, Uzunoglu D, Kocyigit BS, Gumus B, Acar T and Tuncer B. Preparation, characterization, and enhanced antimicrobial activity: quercetin-loaded PLGA
nanoparticles against foodborne pathogens. Turk. J.Biol. (2017) 41: 127-40.
(7) Nabavi SF, Russo GL, Daglia M and Nabavi SM. Role of quercetin as an alternative for obesity treatment: You are what you eat! Food Chem. (2015)179: 305-10.
(8) Machha A, Achike FI, Mustafa AM and MustafaMR. Quercetin, a flavonoid antioxidant, modulates endothelium-derived nitric oxide bioavailability indiabetic rat aortas. Nitric Oxide (2007) 16: 442-7.
(9) Jain AK, Thanki K and Jain S. Co-encapsulation of tamoxifen and quercetin in polymeric nanoparticles: implications on oral bioavailability, antitumor
efficacy, and drug-induced toxicity. Mol. Pharm.(2013) 10: 3459-74.
(10) Kumari A, Yadav SK, Pakade YB, Singh Band Yadav SC. Development of biodegradable nanoparticles for delivery of quercetin. Colloids Surf., B. (2010) 80: 184-92.
(11) Sun M, Nie S, Pan X, Zhang R, Fan Z and Wang S. Quercetin-nanostructured lipid carriers:
characteristics and anti-breast cancer activities invitro. Colloids Surf., B. (2014) 113: 15-24.
(12) Cai X, Fang Z, Dou J, Yu A and Zhai G. Bioavailability of quercetin: problems and promises. Curr. Med. Chem. (2013) 20: 2572-82.
(13) Nune SK, Gunda P, Thallapally PK, Lin Y-Y,Laird Forrest M and Berkland CJ. Nanoparticlesfor biomedical imaging. Expert. Opin Drug Deliv.(2009) 6: 1175-94.
(14) Arasoglu T, Derman S and Mansuroglu B.Comparative evaluation of antibacterial activity ofcaffeic acid phenethyl ester and PLGA nanoparticleformulation by different methods.Nanotechnology(2015) 27: 1-12.
(15) Vyas SP and Khar RK. Targeted & Controlled DrugDelivery: Novel Carrier Systems. CBS publishers& distributors (2004).
(16) Arasoglu T, Mansuroglu B, Derman S, GumusB, Kocyigit B, Acar T and Kocacaliskan I.Enhancement of Antifungal Activity of Juglone(5-Hydroxy-1, 4-naphthoquinone) Using a Poly(d, l-lactic-co-glycolic acid)(PLGA) NanoparticleSystem. J. Agric. Food Chem. (2016) 64: 7087-94.
(17) Mohanraj V and Chen Y. Nanoparticles-a review.Trop. J. Pharm. Res. (2007) 5: 561-73.
(18) Rao JP and Geckeler KE. Polymer nanoparticles:preparation techniques and size-control parameters.Prog. Polym. Sci. (2011) 36: 887-913.
(19) Muhamad I., Selvakumaran S and Lazim NA.Designing Polymeric Nanoparticles for TargetedDrug Delivery System. In: Seifalian A, Mel A andKalaskar DM. (eds.) Nanomedicine. 1st ed. OneCentral Press (OCP) (2014) 287-13.
(20) Halayqa M and Domańska U. PLGA BiodegradableNanoparticles Containing Perphenazine orChlorpromazine Hydrochloride: Effect ofFormulation and Release. Int. J. Mol. Sci. (2014)
15: 23909-23.
(21) Dangi R and Shakya S. Preparation, optimizationand characterization of PLGA nanoparticle. Int. J.Pharm. Life Sci. (2013) 4: 2810-2818
(22) Michanetzis GP, Missirlis YF and Antimisiaris SG.Haemocompatibility of nanosized drug deliverysystems: has it been adequately considered? J.Biomed. Nanotechnol. (2008) 4: 218-33.
(23) Alves AdCS, Mainardes RM and Khalil NM.Nanoencapsulation of gallic acid and evaluation ofits cytotoxicity and antioxidant activity. Mat. Sci.Eng. C-Mater. (2016) 60: 126-34.
(24) Fornaguera C, Calderó G, Mitjans M, VinardellMP, Solans C and Vauthier C. Interactions ofPLGA nanoparticles with blood components:protein adsorption, coagulation, activation ofthe complement system and hemolysis studies.Nanoscale (2015) 7: 6045-58.
(25) Derman S and Akdeste ZM. Particle size and zetapotential investigation of synthetic peptide-proteinconjugates/Sentetik peptid-protein konjugatlarınınparçacık boyutu ve zeta potensiyel analizi. Turk. J.Biochem. (2015) 40: 282-9.
(26) Arasoglu T, Derman S, Mansuroglu B, Yelkenci G,Kocyigit B, Gumus B, Acar T and Kocacaliskan I.Synthesis, characterization and antibacterial activityof juglone encapsulated PLGA nanoparticles. J.Appl. Microbiol. (2017) 123: 1407-19.
(27) Derman S. Caffeic acid phenethyl ester loadedPLGA nanoparticles: effect of various process 435Derman S et al. / IJPR (2020), 19 (1): 424-435parameters on reaction yield, encapsulationefficiency, and particle size. J. Nanomater. (2015)16: 318.
(28) Derman S, Mustafaeva ZA, Abamor ES,Bagirova M and Allahverdiyev A. Preparation,characterization and immunological evaluation:canine parvovirus synthetic peptide loaded PLGAnanoparticles. J. Biomed. Sci. (2015) 22: 1-12.
(29) McCord JM and Fridovich I. Superoxidedismutase an enzymic function for erythrocuprein(hemocuprein). J. Biol. Chem. (1969) 244: 6049-55.
(30) Drabkin DL and Austin JH. Spectrophotometricstudies II. Preparations from washed blood cells;nitric oxide hemoglobin and sulfhemoglobin. J.Biol. Chem. (1935) 112: 51-65.
(31) Song X, Zhao Y, Hou S, Xu F, Zhao R, He J, CaiZ, Li Y and Chen Q. Dual agents loaded PLGAnanoparticles: systematic study of particle sizeand drug entrapment efficiency. Eur. J. PharmBiopharm. (2008) 69: 445-53.
(32) Shi W, Zhang Z-j, Yuan Y, Xing E-m, Qin Y, PengZ-j, Zhang Z-p and Yang K-y. Optimization ofparameters for preparation of docetaxel-loadedPLGA nanoparticles by nanoprecipitation method.J. Huazhong U Sci-Med. (2013) 33: 754-8.
(33) Song X, Zhao Y, Wu W, Bi Y, Cai Z, Chen Q, LiY and Hou S. PLGA nanoparticles simultaneouslyloaded with vincristine sulfate and verapamilhydrochloride: systematic study of particle size anddrug entrapment efficiency. Int. J. Pharm. (2008)350: 320-9.
(34) Zhou YZ, Alany RG, Chuang V and Wen J.Optimization of PLGA nanoparticles formulationcontaining L-DOPA by applying the centralcomposite design. Drug Dev. Ind. Pharm. (2013)
39: 321-30.
(35) Sharma N, Madan P and Lin S. Effect of processand formulation variables on the preparationof parenteral paclitaxel-loaded biodegradablepolymeric nanoparticles: A co-surfactant study.Asian J. Pharm. Sci. (2016) 11: 404-16.
(36) Hussein AS, Abdullah N, and Fakru’l‐raziA. Optimizing the Process Parameters forEncapsulation of Linamarin into PLGANanoparticles Using Double Emulsion SolventEvaporation Technique. Adv. Polym. Tech. (2013)32: E486-E504.
(37) Ghasemian E, Vatanara A, Najafabadi AR,Rouini MR, Gilani K, and Darabi M. Preparation,characterization and optimization of sildenafilcitrate loaded PLGA nanoparticles by statisticalfactorial design. DARU (2013) 21: 68.
(38) Pool H, Quintanar D, de Dios Figueroa J, ManoCM, Bechara JEH, Godínez LA and MendozaS. Antioxidant effects of quercetin and catechinencapsulated into PLGA nanoparticles. J.Nanomater. (2012) 2012: 86.
(39) Sun D, Li N, Zhang W, Yang E, Mou Z, ZhaoZ, Liu H and Wang W. Quercetin-loaded PLGAnanoparticles: a highly effective antibacterial agentin-vitro and anti-infection application in-vivo. J.Nanopar. Res. (2016) 18: 3.
(40) Win KY and Feng S-S. Effects of particle size andsurface coating on cellular uptake of polymericnanoparticles for oral delivery of anticancer drugs.Biomaterials (2005) 26: 2713-22.
(41) Redhead H, Davis S and Illum L. Drug deliveryin poly (lactide-co-glycolide) nanoparticles surfacemodified with poloxamer 407 and poloxamine 908:in-vitro characterisation and in-vivo evaluation. J.Control Release (2001) 70: 353-63.
(42) Surolia R, Pachauri M and Ghosh PC. Preparationand characterization of monensin loaded PLGAnanoparticles: in-vitro anti-malarial activity againstPlasmodium falciparum. J. Biomed. Nanotechnol.(2012) 8: 172-81.
(43) Luo R, Neu B and Venkatraman SS. Surfacefunctionalization of nanoparticles to control cellinteractions and drug release. Small (2012) 8:2585-94.
(44) Shen X, Li T, Chen Z, Geng Y, Xie X, Li S,Yang H, Wu C and Liu Y. Luminescent/magneticPLGA-based hybrid nanocomposites: a smartnanocarrier system for targeted codelivery anddual-modality imaging in cancer theranostics. Int.J. Nanomedicine (2017) 12: 4299.
(45) Pillai GJ, Greeshma M and Menon D. Impact ofpoly (lactic-co-glycolic acid) nanoparticle surfacecharge on protein, cellular and haematologicalinteractions. Colloid Surf., B. (2015) 136: 1058-66.