Studying the Effect of Functional Group and Size of Silica Nanoparticles Loaded with Quercetin on their in vitro Characteristics
DOI:
https://doi.org/10.35516/jjps.v15i4.679Keywords:
Silica nanoparticles, quercetin, surface functionalization, size of SNs, DLS analysis, cumulative release, MTT assayAbstract
Silica nanoparticles (SNs) possess unique properties making them ideal carriers for many agents. Both the size and the surface chemistry are important features that impact the in vitro characteristics of their loaded agents. In this study, different surface functionalization of SNs with a particle size of 200 nm (propyl thiol, propyl carboxylic acid, and propyl amine) and two different sizes of propyl amine SNs (200 and less than 100 nm) were investigated. The nanoparticles (NPs) parameters were characterized using Dynamic Light Scattering (DLS) and their Encapsulation Efficiency (EE) and Loading Capacity (LC) with quercetin were measured using UV Spectrophotometer. Quercetin cumulative release was studied in phosphate buffer saline (PBS) (pH 7.4, 37°C) and its in vitro cytotoxicity toward HeLa cells was evaluated using an MTT assay. Our results showed that the mean particle size of all samples increased after drug loading and the polydispersity (PD) values were all within the acceptable range (0.2-0.5). All SNs exhibited negative values of zeta potential with the highest value for propyl-carboxylated NPs. The EE and LC percentages of quercetin in SNs depend on the type of surface functional group where the aminated SNs showed higher percentages compared to the other groups. A direct relation was observed between the drug release rate and the cytotoxicity where the highest and smallest values were exhibited by thiolated and aminated SNs, respectively. Surface modifications have thus a more pronounced effect on the in vitro properties of our studied SNs compared to the size.
References
Shi J, Votruba AR, Farokhzad OC, Langer R. Nanotechnology in drug delivery and tissue engineering: From discovery to applications. Nano Lett. 2010;10(9):3223-3230. doi:10.1021/nl102184c
Mohanraj VJ, Chen Y. Nanoparticles - A review. Trop J Pharm Res. 2007; 5(1):561-573.
doi:10.4314/tjpr.v5i1.14634
Kzar HH, Al-Gazally ME, Wtwt MA. Everolimus loaded NPs with FOL targeting: preparation, characterization and study of its cytotoxicity action on MCF-7 breast cancer cell lines. Jordan Journal of Pharmaceutical Sciences 2022;15(1):25-39. doi:10.35516/jjps.v15i1.286
Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H. Nanoparticles as drug delivery systemspl (concerning chemistry of nanoparticles). Pharmacol Reports. 2012;64(5):1020-1037.
doi:10.1016/S1734-1140(12)70901-5
Desai MP, Labhasetwar V, Walter E, Levy RJ, Amidon GL. The mechanism of uptake of biodegradable microparticles in Caco-2 cells is size dependent. Pharm Res. 1997; 14(11): 1568-1573.
doi:10.1023/A:1012126301290
Khattabi AM, Alqdeimat DA, Sabbar E, Talib WH. In vitro characteristics of a combination of thymoquinone-resveratrol loaded and targeted nanodrug delivery system. Jordan Journal of Pharmaceutical Sciences 2020;13(1):53-64.
Slowing II, Trewyn BG, Giri S, Lin VSY. Mesoporous silica nanoparticles for drug delivery and biosensing applications. Adv Funct Mater. 2007;17(8):1225-1236. doi:10.1002/adfm.200601191
Vivero-Escoto JL, Slowing II, Lin VSY, Trewyn BG. Mesoporous silica nanoparticles for intracellular controlled drug delivery. Small. 2010;6(18):1952-1967. doi:10.1002/smll.200901789
Chiang YD, Lian HY, Leo SY, Wang SG, Yamauchi Y, Wu KCW. Controlling particle size and structural properties of mesoporous silica nanoparticles using the taguchi method. J Phys Chem C. 2011;115(27):13158-13165. doi:10.1021/jp201017e
Lu F, Wu SH, Hung Y, Mou CY. Size effect on cell uptake in well-suspended, uniform mesoporous silica nanoparticles. Small. 2009;5(12):1408-1413.
doi:10.1002/smll.200900005
Trewyn BG, Nieweg JA, Zhao Y, Lin VSY. Biocompatible mesoporous silica nanoparticles with different morphologies for animal cell membrane penetration. Chem Eng J. 2008;137(1):23-29. doi:10.1016/j.cej.2007.09.045
Lankoff A, Arabski M, Wegierek-Ciuk A, et al. Effect of surface modification of silica nanoparticles on toxicity and cellular uptake by human peripheral blood lymphocytes in vitro. Nanotoxicology. 2013;7(3):235-250. doi:10.3109/17435390.2011.649796
Hoshyar N, Gray S, Han H, Bao G. The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction. Nanomedicine. 2016;11(6):673-692. doi:10.2217/nnm.16.5
Lin Y-Q, Zhang J, Liu S-J, Ye H. Doxorubicin Loaded Silica Nanoparticles with Dual Modification as a Tumor-Targeted Drug Delivery System for Colon Cancer Therapy. J Nanosci Nanotechnol. 2017;18(4):2330-2336. doi:10.1166/jnn.2018.14391
Halo M, Ferrari AM, Berlier G, Miletto I, Casassa S. Experimental and first-principles IR characterization of quercetin adsorbed on a silica surface. Theor Chem Acc. 2016;135(5):1-8. doi:10.1007/s00214-016-1854-4
Formica J V., Regelson W. Review of the biology of quercetin and related bioflavonoids. Food Chem Toxicol. 1995;33(12):1061-1080.
doi:10.1016/0278-6915(95)00077-1
Buchner N, Krumbein A, Rohn S, Kroh LW. Effect of thermal processing on the flavonols rutin and quercetin. 2006:3229-3235. doi:10.1002/rcm
Dehghan G, Khoshkam Z. Tin ( II )– quercetin complex : Synthesis, spectral characterisation and antioxidant activity. Food Chem. 2012;131(2):422-426.
doi:10.1016/j.foodchem.2011.08.074
Moon YJ, Wang L, Dicenzo R, Morris ME. Quercetin Pharmacokinetics in Humans. 2008;217(August 2007):205-217. doi:10.1002/bdd
Wang W, Sun C, Mao L, et al. Trends in Food Science & Technology The biological activities , chemical stability, metabolism and delivery systems of quercetin : A review. Trends Food Sci Technol. 2016;56:21-38.
doi:10.1016/j.tifs.2016.07.004
Sharma A, Kashyap D, Sak K, Tuli HS, Sharma AK. Therapeutic charm of quercetin and its derivatives: a review of research and patents. Pharm Pat Anal. 2018;7(1):15-32. doi:10.4155/ppa-2017-0030
Sarkar A, Ghosh S, Chowdhury S, Pandey B, Sil PC. Targeted delivery of quercetin loaded mesoporous silica nanoparticles to the breast cancer cells. Biochim Biophys Acta - Gen Subj. 2016;1860(10):2065-2075.
doi:10.1016/j.bbagen.2016.07.001
Hwang JT, Kwon DY, Yoon SH. AMP-activated protein kinase: a potential target for the diseases prevention by natural occurring polyphenols. N Biotechnol. 2009;26 (1-2):17-22. doi:10.1016/j.nbt.2009.03.005
D’Andrea G. Quercetin: A flavonol with multifaceted therapeutic applications? Fitoterapia. 2015;106:256-271. doi:10.1016/j.fitote.2015.09.018
Heijnen CGM, Haenen GRMM, Oostveen RM, Stalpers EM, Bast A. Protection of flavonoids against lipid peroxidation: The structure activity relationship revisited. Free Radic Res. 2002;36(5):575-581.
doi:10.1080/10715760290025951
Ansari MA, Abdul HM, Joshi G, Opii WO, Butterfield DA. Protective effect of quercetin in primary neurons against Aβ(1-42): relevance to Alzheimer’s disease. J Nutr Biochem. 2009;20(4):269-275.
doi:10.1016/j.jnutbio.2008.03.002
Rauf A, Imran M, Khan IA, et al. Anticancer potential of quercetin: A comprehensive review. Phyther Res. 2018;32(11):2109-2130. doi:10.1002/ptr.6155
Najafi M, Tavakol S, Zarrabi A, Ashrafizadeh M. Dual role of quercetin in enhancing the efficacy of cisplatin in chemotherapy and protection against its side effects: a review. Arch Physiol Biochem. 2020;0(0):1-15.
doi:10.1080/13813455.2020.1773864
Srinivas K, King JW, Howard LR, Monrad JK. Solubility and solution thermodynamic properties of quercetin and quercetin dihydrate in subcritical water. J Food Eng. 2010;100(2):208-218. doi:10.1016/j.jfoodeng.2010.04.001
Priprem A, Watanatorn J, Sutthiparinyanont S, Phachonpai W, Muchimapura S. Anxiety and cognitive effects of quercetin liposomes in rats. 2008;4:70-78. doi:10.1016/j.nano.2007.12.001
Gugler R, Leschik M, Dengler HJ. Disposition of quercetin in man after single oral and intravenous doses. Eur J Clin Pharmacol. 1975;9(2-3):229-234.
doi:10.1007/BF00614022
Li HL, Zhao X Bin, Ma YK, Zhai GX, Li LB, Lou HX. Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles. J Control Release. 2009;133(3):238-244. doi:10.1016/j.jconrel.2008.10.002
Da Silva TA, Gomes JHR, De Bulhões LCG, et al. Therapeutic potential of quercetin based on nanotechnology: A review. Rev Virtual Quim. 2019;11(4):1405-1416.
doi:10.21577/1984-6835.20190096
Cai X, Fang Z, Dou J, Yu A, Zhai G. Send Orders of Reprints at reprints@benthamscience.net Bioavailability of Quercetin: Problems and Promises. Curr Med Chem. 2013;20:2572-2582.
Day AJ, Bao Y, Morgan MRA, Williamson G. Conjugation position of quercetin glucuronides and effect on biological activity. Free Radic Biol Med. 2000;29(12):1234-1243.
doi:10.1016/S0891-5849(00)00416-0
Tan Q, Liu W, Guo C, Zhai G. Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery. Int J Nanomedicine. 2011;6:1621-1630.
Nday CM, Halevas E, Jackson GE, Salifoglou A. Quercetin encapsulation in modified silica nanoparticles: potential use against Cu(II)-induced oxidative stress in neurodegeneration. J Inorg Biochem. 2015;145(Ii):51-64. doi:10.1016/j.jinorgbio.2015.01.001
Khattabi AM, Talib WH, Alqdeimat DA. A targeted drug delivery system of anti-cancer agents based on folic acid-cyclodextrin-long polymer functionalized silica nanoparticles. J Drug Deliv Sci Technol. 2017;41:367-374. doi:10.1016/j.jddst.2017.07.025
Khattabi AM, Alqdeimat DA. The effect of cyclodextrin on both the agglomeration and the in vitro characteristics of drug loaded and targeted silica nanoparticles. IOP Conf Ser Mater Sci Eng. 2018;305(1). doi:10.1088/1757-899X/305/1/012008
Chaudhari S, Mannan A, Daswadkar S. Development and validation of UV spectrophotometric method for simultaneous estimation of Acyclovir and Silymarin in niosome formulation. Der Pharm Lett. 2016;8(5):128-133.
Dora CP, Singh SK, Kumar S, Datusalia AK, Deep A. Development and characterization of nanoparticles of glibenclamide by solvent displacement method. Acta Pol Pharm - Drug Res. 2010;67(3):283-290.
Bolouki A, Rashidi L, Vasheghani-Farahani E, Piravi-Vanak Z. Study of Mesoporous Silica Nanoparticles as Nanocarriers for Sustained Release of Curcumin. Int J Nanosci Nanotechnol. 2015;11(3):139-146.
Mohammadpour Dounighi N, Damavandi M, Zolfagharian H, Moradi S. Preparing and characterizing chitosan nanoparticles containing hemiscorpius lepturus scorpion venom as an antigen delivery system. Arch Razi Inst. 2012;67(2):145-153.
Sreeram KJ, Nidhin M, Indumathy R, Nair BU. Synthesis of iron oxide nanoparticles of narrow size distribution on polysaccharide templates. Bull Mater Sci. 2008;31(1):93-96. doi:10.1007/s12034-008-0016-2
Gaikwad VL, Choudhari PB, Bhatia NM, Bhatia MS. Characterization of Pharmaceutical Nanocarriers: In Vitro and in Vivo Studies. Elsevier Inc.; 2019. doi:10.1016/B978-0-12-816505-8.00016-3
Kumar R. Lipid-Based Nanoparticles for Drug-Delivery Systems. Elsevier Inc.; 2019. doi:10.1016/b978-0-12-814033-8.00008-4
Barba AA, Bochicchio S, Dalmoro A, Caccavo D, Cascone S, Lamberti G. Polymeric and Lipid-Based Systems for Controlled Drug Release: An Engineering Point of View. Elsevier Inc.; 2019. doi:10.1016/B978-0-12-816505-8.00013-8
Umr L, Mitterrand BF, Maupertuis B. The Silica − Water Interface: How the Silanols Determine the Surface Acidity and Modulate the Water Properties. J Chem Theory Comput. 2012;8:1037-1047.
Hocker S, Rhudy AK, Ginsburg G, Kranbuehl DE. Polyamide hydrolysis accelerated by small weak organic acids. Polymer (Guildf). 2014;55(20):5057-5064. doi:10.1016/j.polymer.2014.08.010
Chebotarev AN, Snigur D V. Study of the acid-base properties of quercetin in aqueous solutions by color measurements. J Anal Chem. 2015;70(1):55-59. doi:10.1134/S1061934815010062
Tang F, Li L, Chen D. Mesoporous silica nanoparticles: Synthesis, biocompatibility and drug delivery. Adv Mater. 2012;24(12):1504-1534.
doi:10.1002/adma.201104763
Jambhrunkar S, Qu Z, Popat A, et al. Effect of surface functionality of silica nanoparticles on cellular uptake and cytotoxicity. Mol Pharm. 2014;11(10):3642-3655. doi:10.1021/mp500385n
Shang L, Nienhaus K, Nienhaus GU. Engineered nanoparticles interacting with cells: Size matters. J Nanobiotechnology. 2014;12(1):1-11. doi:10.1186/1477-3155-12-5
Panariti A, Miserocchi G, Rivolta I. The effect of nanoparticle uptake on cellular behavior: Disrupting or enabling functions? Nanotechnol Sci Appl. 2012;5(1):87-100. doi:10.2147/NSA.S25515
Bhattacharjee S, de Haan LHJ, Evers NM, et al. Role of surface charge and oxidative stress in cytotoxicity of organic monolayer-coated silicon nanoparticles towards macrophage NR8383 cells. Part Fibre Toxicol. 2010;7:25. doi:10.1186/1743-8977-7-25