Original Article

Therapeutic Effect of Chitosan Nanoparticles and Metronidazole in Treatment of Experimentally Giardiasis Infected Hamsters

Abstract

Background: The present study aimed to assess the therapeutic effect of chitosan nanoparticles and metronidazole against Giardia lamblia as well as evaluate the efficacy of loading metronidazole on chitosan nanoparticles.

Methods: This study was carried out at medical Parasitology Department, Faculty of Medicine, Zagazig University and Theodor Bilharz Research institute (TBRI) from February 2019 to February 2020 on 45 hamsters. They were divided into 5 groups 9 hamsters each: Group A non-infected hamsters, Group B infected control group, Group C, D and E infected with G. lamblia and treated with Chitosan nanoparticles (CsNPs), metronidazole (MTZ) and metronidazole-loaded chitosan nanoparticles (MTZ-CsNPs) respectively.

Results: The highest percentage of reduction in the Giardia cyst and trophozoite counts were in group that received MTZ-CsNPs (94.69%, 94.29%). Lower percentages of reduction were recorded for MTZ treated group (90.15%, 89.52%) and CsNPs treated group (63.64%, 75.24%). Histopathological examination showed marked healing of intestinal mucosa after treatment with MTZ-CsNPs.

Conclusion: CsNPs showed a therapeutic effect against Giardia infection in hamsters. Loading of metronidazole on chitosan nanoparticles enhanced therapeutic effect of both CsNPs as well as metronidazole.

1. Pecková R, Doležal K, Sak B, et al. Effect of piper betle on Giardia intestinalis infection in vivo. Exp Par-asitol. 2018; 184:39–45.
2. Dyab AK, Yones DA, Ibraheim Z, et al. Anti-giardial therapeutic potential of dichloromethane ex-tracts of Zingiber officinale and curcuma longa in vitro and in vivo. Parasitol Res. 2016; 115(7):2637–45.
3. Magill AJ, Ryan ET, Solomon T, et al. Hunter’s Tropical Medicine and Emerging Infectious Dis-ease. 9th edition. USA, Saunders an imprint of Elsevier Inc 2012. Available from: https://linkinghub.elsevier.com/retrieve/pii/C20090519344
4. Bope ET, Kellerman RD. Conn's current therapy 2015 E-Book. 1st Edition. USA, Elsevier Health Sciences 2014. Available from: https://books.google.com.jm/books?id=Hv8fBQAAQBAJ
5. Harris JC, Plummer S, Lloyd D. Antigiardial drugs. Appl Microbiol Biotechnol. 2001; 57(1):614–9.
6. Said DE, ElSamad LM, Gohar YM. Validity of silver, chitosan, and curcumin nanoparticles as anti-giardia agents. Parasitol Res. 2012; 111(2): 545–54.
7. Yah CS, Simate GS. Nanoparticles as potential new generation broad spectrum antimicrobial agents. Daru. 2015; 23:43.
8. Yarahmadi M, Fakhar M, Ebrahimzadeh MA, et al. The anti-giardial effectiveness of fungal and com-mercial chitosan against Giardia intestinalis cysts in vitro. J Parasit Dis. 2016; 40(1):75–80.
9. Aly MM, Shalaby MA, Attia SS, et al. Therapeutic Effect of Lauric Acid, a Medium Chain Saturated Fatty Acid on Giardia lamblia in Experimentally In-fected Hamsters.Parasitol United J.2013;6(1):89-98.
10. Ammar IA, Mahmoud SS, El Hefnawy NN. Ef-fect of ginger on hamsters infected by Giardia lamblia. J Environ Stud Res .2014;1(1):45–56.
11. Elzatahry AA, Eldin MSM. Preparation and charac-terization of metronidazole-loaded chitosan nano-particles for drug delivery application. Polym Adv Technol. 2008; 19(12):1787–91.
12. Slaoui M, Fiette L. Histopathology procedures: from tissue sampling to histopathological evaluation. Methods Mol Biol. 2011; 691:69-82.
13. Tendler M, Pinto R.M, Oliveira lima A, et al. Schisto-soma mansoni: vaccination with adult worm antigens. Int J Parasitol. 1986; 16(4): 347-52.
14. Adam RD. Biology of Giardia lamblia. Clin Microbiol Rev. 2001; 14(3):447–75.
15. Farrar J, Hotez PJ, Junghanss T, et al. Manson’s Tropical Diseases. 23th edition. USA, Saunders an imprint of Elsevier Inc 2014. https://www.elsevier.com/books/mansons-tropical-infectious-diseases/9780702051012
16. Halliez MC, Buret AG. Extra-intestinal and long term consequences of Giardia duodenalis infections. World J Gastroenterol. 2013; 19(47):8974-85.
17. Müller J, Hemphill A, Müller N. Physiological as-pects of nitro drug resistance in Giardia lamblia. Int J Parasitol Drugs Drug Resist. 2018; 8(2):271–7.
18. Qi L, Xu Z, Jiang X, et al. Preparation and antibac-terial activity of chitosan nanoparticles. Carbohydr Res. 2004; 339(16):2693–700.
19. Nagpal K, Singh SK, Mishra DN. Chitosan nano-particles: a promising system in novel drug delivery. Chem Pharm Bull (Tokyo). 2010; 58(11):1423–30.
20. Wang JJ, Zeng Z, Xiao RZ, et al. Recent advances of chitosan nanoparticles as drug carriers. Int J Na-nomedicine. 2011; 6:765-74.
21. Goy RC, De-Britto D, Assis OBG. A review of the antimicrobial activity of chitosan. Polímeros. 2009; 19(3):241-7. https://doi.org/10.1590/S0104-14282009000300013
22. Busatti HG, Santos JF, Gomes MA. The old and new therapeutic approaches to the treatment of gi-ardiasis: Where are we? Biologics. 2009; 3:273-87.
23. Gardner TB, Hill DR. Treatment of Giardiasis. Clin Microbiol Rev. 2001; 14(1):114–28.
24. Lemée V, Zaharia I, Nevez G, et al. Metronidazole and albendazole susceptibility of 11 clinical isolates of Giardia duodenalis from France. J Antimicrob Chemother. 2000; 46(5):819–21.
25. Ansell BR, McConville MJ, Ma’ayeh SY, et al. Drug resistance in Giardia duodenalis. Biotechnol Adv. 2015; 33(6 Pt 1):888–901.
26. Ruchika H. Formulation and evaluation of metroni-dazole loaded chitosan nanoparticles. Int J Sci Res Methodol. 2016; 4(4):1–17. https://ijsrm.humanjournals.com/formulation-and-evaluation-of-metronidazole-loaded-chitosan-nanoparticles/
27. Abulaihaiti M, Wu XW, Qiao L, et al. Efficacy of albendazole-chitosan microsphere-based treatment for Alveolar echinococcosis in mice. PLOS Negl Trop Dis. 2015; 9(9):e0003950.
28. Saber AE, Abdelwahab AK, El Amir AM, et al. Bee venom loaded chitosan nanoparticles as treat-ment for amoebiasis in mice. J Egypt Soc Parasitol. 2017; 47(2):443–58.
29. Jabir NR, Tabrez S, Ashraf GM, et al. Nanotech-nology-based approaches in anticancer research. Int J Nanomedicine. 2012; 7:4391–408.
30. Elgadir MA, Uddin MS, Ferdosh S, et al. Impact of chitosan composites and chitosan nanoparticle composites on various drug delivery systems: A re-view. J Food Drug Anal. 2015; 23(4):619–29.
31. Chabra A, Rahimi-Esboei B, Habibi E, et al. Ef-fects of some natural products from fungal and herbal sources on Giardia lamblia in vivo. Parasitolo-gy. 2019; 146(9):1188-98.
32. Muñoz Gutiérrez J, Aldasoro E, Requena A, et al. Refractory giardiasis in Spanish travelers. Travel Med Infect Dis. 2013; 11(2):126–9.
33. Hagras NA, Allam AF, Farag HF, et al. Successful treatment of acute experimental toxoplasmosis by spiramycin-loaded chitosan nanoparticles. Exp Par-asitol. 2019; 204:107717.
34. Garcia LS. Diagnostic Medical Parasitology. 5th edition. Am Soc Microbiol 2007. Available from: http://www.asmscience.org/content/book/10.1128/9781555816018
35. Varma D, Jain S, Khurana N. Role of gastric brush cytology in the diagnosis of giardiasis. J Cytol 2008; 25:55-7.
36. Han XY, Du WL, Huang QC, et al. Changes in small intestinal morphology and digestive enzyme activity with oral administration of copper-loaded chitosan nanoparticles in rats. Biol Trace Elem Res. 2012; 145(3):355-60.
37. Ahmed TA, Aljaeid BM. Preparation, characteriza-tion, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery. Drug Des Devel Ther. 2016; 10:483–507.
38. Wardani G, Eraiko K, Koerniasari K, et al. Protec-tive activity of chitosan nanoparticle against cadmi-um chloride induced gastric toxicity in rat. J Young Pharm. 2018; 10(3):303–7.
39. Kim S. Competitive biological activities of chitosan and its derivatives: antimicrobial, antioxidant, anti-cancer, and anti-inflammatory activities. Int J Polym Sci. 2018; 2018:1-13.
40. Hu YL, Qi W, Han F, et al. Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model. Int J Nanomedicine. 2011; 6:3351-9.
41. Leffler DA, Lamont JT. Treatment of Clostridium difficile-associated Disease. Gastroenterology. 2009; 136(6):1899–912.
42. Pélissier MA, Vasquez N, Balamurugan R, et al. Metronidazole effects on microbiota and mucus layer thickness in the rat gut. FEMS Microbiol Ecol. 2010; 73(3):601–10.
43. Adil M, Iqbal W, Adnan F, et al. Association of Metronidazole with Cancer: A Potential Risk Factor or Inconsistent Deductions? Curr Drug Metab. 2018; 19(11):902-9.
44. Hanevik K, Hausken T, Morken MH, et al. Persist-ing symptoms and duodenal inflammation related to Giardia duodenalis infection. J Infect. 2007; 55(6):524-30.
45. Raţa DM, Cadinoiu AN, Daraba O, et al. Metroni-dazole- loaded chitosan/poly (maleic anhydride-alt-vinyl acetate) hydrogels for dental treatments. Int J Med Dent 2016; 20(2):92-97.
46. Ali A, Ahmed S. A review on chitosan and its nanocomposites in drug delivery. Int J Biol Mac-romol. 2018; 109:273–86.
Files
IssueVol 16 No 1 (2021) QRcode
SectionOriginal Article(s)
Published2021-02-16
DOI https://doi.org/10.18502/ijpa.v16i1.5509
Keywords
Chitosan nanoparticles Metronidazole Giardia lamblia Metronidazole-loaded chi-tosan nanoparticles

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
El-GENDY A, MOHAMMED M, GHALLAB M, ABDEL AZIZ M, IBRAHIM S. Therapeutic Effect of Chitosan Nanoparticles and Metronidazole in Treatment of Experimentally Giardiasis Infected Hamsters. Iran J Parasitol. 16(1):32-42.