Synthesis and evaluation of anti‐inflammatory properties of hydroxyapatite nanoparticles in an experimental model of colitis

Document Type : Research Paper

Authors

1 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

6 Medical Genetics Research center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

7 Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Ulcerative colitis (UC) is a chronic large intestinal condition, for treatment and prevention of which sulfasalazine (SSZ) is used. It functions by helping to reduce inflammation and other disease symptoms within the bowels, but this drug has many side effects. Various novel paths for UC treatment are being studied to solve the difficulties associated with present treatments and to design a more targeted therapy. Hydroxyapatite nanoparticles (HAP-NPs) form an inorganic portion of the natural bone and are primarily used in tissue engineering due to their anti-inflammatory and anti-toxicity character. This study aimed to investigate the anti-inflammatory character of sulfasalazine-containing HAP (SSZ-HAP-NPs) as a potential therapeutic agent.
Materials and Methods: The therapeutic efficacy of SSZ-HAP-NPs compared with SSZ as a standard drug was examined in a mouse model of colitis by induction of DSS for 7 days. Drugs were given on the third day and continued for seven days. Colonic mucosal inflammation was evaluated clinically, biochemically, and histologically.
Results: Our results showed that SSZ-HAP-NPs clinically improved signs/symptoms more than SSZ, however, it was not statistically significant (P>0.05). Also, SSZ-HAP-NPs diminished histopathological evidence of injury, by decreasing inflammatory responses and balancing oxidative/anti-oxidative markers in colonic tissues (P>0.05). 
Conclusion: SSZ-HAP-NPs could be more effective than SSZ as standard drug in some laboratory and clinical signs/symptoms and side effects in colitis and this could be a good strategy for future studies to use nanoparticles with more anti-inflammatory effects to develop the efficiency of standard drugs in colitis treatment.

Keywords

References

1.    Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. The Lancet. 2007;369(9573):1627-40.
2.    Biasi F, Leonarduzzi G, Oteiza PI, Poli G. Inflammatory bowel disease: mechanisms, redox considerations, and therapeutic targets. Antioxid Redox Signal. 2013;19(14):1711-1747.
3.    Neurath MF. Current and emerging therapeutic targets for IBD. Nat. Rev. Gastroenterol. Hepatol. 2017;14(5):269-78.
4.    Naeem M, Awan UA, Subhan F, Cao J, Hlaing SP, Lee J, et al. Advances in colon-targeted nano-drug delivery systems: challenges and solutions. Arch Pharm Res. 2020:1-17.
5.    Hua S, Marks E, Schneider JJ, Keely S. Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue. Nanomed.: Nanotechnol Biol Med. 2015;11(5):1117-1132.
6.    Zhu S, Huang B, Zhou K, Huang S, Liu F, Li Y, et al. Hydroxyapatite nanoparticles as a novel gene carrier. J Nanopart Res. 2004;6(2):307-311.
7.    Syamchand SS, Sony G. Multifunctional hydroxyapatite nanoparticles for drug delivery and multimodal molecular imaging. Microchimica Acta. 2015;182(9-10):1567-1589.
8.    Asgharzadeh F, Hashemzadeh A, Yaghoubi A, Avan A, Nazari SE, Soleimanpour S, et al. Therapeutic effects of silver nanoparticle containing sulfasalazine on DSS-induced colitis model. J Drug Deliv Sci Technol. 2020;121(9-10):1257-1269.
9.    Kadu K, Tripathi R, Kowshik M, Ramanan SR. Morphological Evolution of Hydroxyapatite Nanoparticles, Synthesized via Modified Sol‐Gel and Microemulsion Technique, in Response to Their Synthesis Microenvironment. Crystal Res and Technol. 2022;114(4-9):1245-1251.
10.    Rahmani F, Asgharzadeh F, Avan A, Barneh F, Parizadeh MR, Ferns GA, et al. Rigosertib potently protects against colitis-associated intestinal fibrosis and inflammation by regulating PI3K/AKT and NF-κB signaling pathways. Life Sci. 2020:117(4-7):1114-1121.
11.    Bargi R, Asgharzadeh F, Beheshti F, Hosseini M, Sadeghnia HR, Khazaei M. The effects of thymoquinone on hippocampal cytokine level, brain oxidative stress status and memory deficits induced by lipopolysaccharide in rats. Cytokine. 2017; 96:173-184.
12.    Cheng K, Weng W, Han G, Du P, Shen G, Yang J, et al. The effect of triethanolamine on the formation of sol–gel derived fluoroapatite/hydroxyapatite solid solution. Mater. Chem. Phys. 2003;78(3):767-771.
13.    Liu D-M, Troczynski T, Tseng WJ. Water-based sol–gel synthesis of hydroxyapatite: process development. Biomaterials. 2001;22(13):1721-1730.
14.    Vakili SN, Rezayi M, Chahkandi M, Meshkat Z, Fani M, Moattari A. A novel electrochemical DNA biosensor based on hydroxyapatite nanoparticles to detect BK polyomavirus in the urine samples of transplant patients. IEEE Sens J. 2020;20(20):12088-95.
15.    Weibel A, Bouchet R, Boulc’ F, Knauth P. The big problem of small particles: a comparison of methods for determination of particle size in nanocrystalline anatase powders. Chem. Mater. 2005;17(9):2378-2385.
16.    Verma G, Shetake NG, Pandrekar S, Pandey B, Hassan P, Priyadarsini K. Development of surface functionalized hydroxyapatite nanoparticles for enhanced specificity towards tumor cells. Eur J Pharm Sci. 2020; 144:105206.
17.    Ai J, Biazar E, Jafarpour M, Montazeri M, Majdi A, Aminifard S, et al. Nanotoxicology and nanoparticle safety in biomedical designs. Int. J. Nanomedicine. 2011; 6:1117.
18.    Guildford A, Poletti T, Osbourne L, Di Cerbo A, Gatti A, Santin M. Nanoparticles of a different source induce different patterns of activation in key biochemical and cellular components of the host response. J R Soc Interface. 2009;6(41):1213-1221.
19.    Yang H, Liu C, Yang D, Zhang H, Xi Z. Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: the role of particle size, shape and composition. J Appl Toxicol. 2009;29(1):69-78.
20.    Albanese A, Tang PS, Chan WC. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu. Rev. Biomed. Eng. 2012; 14:1-16.
21.    Gratton SE, Ropp PA, Pohlhaus PD, Luft JC, Madden VJ, Napier ME, et al. The effect of particle design on cellular internalization pathways. Proc. Natl. Acad. Sci. 2008;105(33):11613-11618.
22.    Laquerriere P, Grandjean-Laquerriere A, Jallot E, Balossier G, Frayssinet P, Guenounou M. Importance of hydroxyapatite particles characteristics on cytokines production by human monocytes in vitro. Biomaterials. 2003;24(16):2739-2747.
23.    Huang J, Best S, Bonfield W, Brooks R, Rushton N, Jayasinghe S, et al. In vitro assessment of the biological response to nano-sized hydroxyapatite. J. Mater. Sci.: Mater. Med. 2004;15(4):441-445.
24.    Lee JH, Ju JE, Kim BI, Pak PJ, Choi EK, Lee HS, et al. Rod‐shaped iron oxide nanoparticles are more toxic than sphere‐shaped nanoparticles to murine macrophage cells. Environ. Toxicol. Chem. 2014;33(12):2759-2766.
25.    Zhao X, Ng S, Heng BC, Guo J, Ma L, Tan TTY, et al. Cytotoxicity of hydroxyapatite nanoparticles is shape and cell dependent. Arch Toxicol. 2013;87(6):1037-1052.
26.    Fan Q, Wang YE, Zhao X, Loo JS, Zuo YY. Adverse biophysical effects of hydroxyapatite nanoparticles on natural pulmonary surfactant. ACS nano. 2011;5(8):6410-6416.
27.    Tay CY, Fang W, Setyawati MI, Chia SL, Tan KS, Hong CHL, et al. Nano-hydroxyapatite and nano-titanium dioxide exhibit different subcellular distribution and apoptotic profile in human oral epithelium. ACS Appl Mater Interfaces. 2014;6(9):6248-6256.
28.    Zhao X, Ong KJ, Ede JD, Stafford JL, Ng KW, Goss GG, et al. Evaluating the toxicity of hydroxyapatite nanoparticles in catfish cells and zebrafish embryos. Small. 2013;9(9‐10):1734-1741.
29.    Shi Z, Huang X, Cai Y, Tang R, Yang D. Size effect of hydroxyapatite nanoparticles on proliferation and apoptosis of osteoblast-like cells. Acta Biomater. 2009;5(1):338-345.
30.    Jin J, Zuo G, Xiong G, Luo H, Li Q, Ma C, et al. The inhibition of lamellar hydroxyapatite and lamellar magnetic hydroxyapatite on the migration and adhesion of breast cancer cells. J Mater Sci Mater Med. 2014;25(4):1025-1031.
31.    Chen X, Deng C, Tang S, Zhang M. Mitochondria-dependent apoptosis induced by nanoscale hydroxyapatite in human gastric cancer SGC-7901 cells. Biol Pharm Bull. 2007;30(1):128-132.
32.    Dey S, Das M, Balla VK. Effect of hydroxyapatite particle size, morphology and crystallinity on proliferation of colon cancer HCT116 cells. Mater Sci Eng C. 2014; 39:336-339.
33.    Ezhaveni S, Yuvakkumar R, Rajkumar M, Sundaram NM, Rajendran V. Preparation and characterization of nano-hydroxyapatite nanomaterials for liver cancer cell treatment. Nanosci Nanotechnol. 2013;13(3):1631-1638.
34.    Di Prospero NA, Sumner CJ, Penzak SR, Ravina B, Fischbeck KH, Taylor JP. Safety, tolerability, and pharmacokinetics of high-dose idebenone in patients with Friedreich ataxia. Arch Neurol. 2007;64(6):803-808.
35.    Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 2014;94(2):329-354.
36.    Tian T, Wang Z, Zhang J. Pathomechanisms of oxidative stress in inflammatory bowel disease and potential antioxidant therapies. Oxid Med Cell Longev. 2017;2017.
37.    Siegel D, Gustafson DL, Dehn DL, Han JY, Boonchoong P, Berliner LJ, et al. NAD (P) H: quinone oxidoreductase 1: role as a superoxide scavenger. Mol Pharmacol. 2004;65(5):1238-1247.
38.    Zhu H, Jia Z, Mahaney JE, Ross D, Misra HP, Trush MA, et al. The highly expressed and inducible endogenous NAD (P) H: quinone oxidoreductase 1 in cardiovascular cells acts as a potential superoxide scavenger. Cardiovasc Toxicol. 2007;7(3):202-211.
39.    Nam ST, Hwang JH, Kim DH, Park MJ, Lee IH, Nam HJ, et al. Role of NADH: quinone oxidoreductase-1 in the tight junctions of colonic epithelial cells. BMB Rep. 2014;47(9):494-499.
40.    Pandurangan AK, Mohebali N, Norhaizan ME, Looi CY. Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice. Drug Des Devel Ther. 2015; 9:3923.
41.    Shafik NM, Gaber RA, Mohamed DA, Ebeid AM. Hesperidin modulates dextran sulfate sodium-induced ulcerative colitis in rats: Targeting sphingosine kinase-1- sphingosine 1 phosphate signaling pathway, mitochondrial biogenesis, inflammation, and apoptosis. J Biochem Mol Toxicol. 2019;33(6):27.
42.    Mellors A, Tappel AL. The inhibition of mitochondrial peroxidation by ubiquinone and ubiquinol. J Biol Chem. 1966;241(19):4353-4356.
43.    Rao R. Oxidative stress-induced disruption of epithelial and endothelial tight junctions. Front Biosci. 2008; 13:7210-26.
44.    Strober W, Fuss IJ. Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology. 2011;140(6):1756-1767.
45.    Geremia A, Biancheri P, Allan P, Corazza GR, Di Sabatino A. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev. 2014;13(1):3-10.
46.    Alex P, Zachos NC, Nguyen T, Gonzales L, Chen TE, Conklin LS, et al. Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis. Inflamm Bowel Dis. 2009;15(3):341-352.
47.    Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol. 2014;14(5):329-342.
48.    Strober W, Fuss IJ, Blumberg RS. The immunology of mucosal models of inflammation. Annu Rev Immunol. 2002; 20:495-549.
Nanomedicine Journal
Volume 9, Issue 4
October 2022
Pages 319-327

Files

Share

How to cite

Statistics