Skip to main content

Advertisement

SpringerLink
Log in

Unravelling Toxoplasma treatment: conventional drugs toward nanomedicine

  • Review
  • Published:
World Journal of Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Toxoplasma gondii is a worldwide protozoan parasite that infects almost all warm-blooded animals. Although human toxoplasmosis is mostly latent, pregnant women and immunocompromised patients need effective treatment. There are drugs of choice for treatment of toxoplasmosis; however, due to their side effects and/or their disease stage-specificity, prescription of them is limited. During recent years, nanomedicine has been employed to overcome limitations of conventional drugs. Here, we provided a state-of-the-art review of experimental toxoplasmosis treatment using nanotechnology.

Graphic abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

All generated data from the current study are included in the article.

References

  • Adeyemi OS, Murata Y, Sugi T, Kato K (2017) Inorganic nanoparticles kill Toxoplasma gondii via changes in redox status and mitochondrial membrane potential. Int J Nanomedicine 12:1647–1661

    Article  PubMed  PubMed Central  Google Scholar 

  • Adeyemi OS, Molefe NI, Awakan OJ, Nwonuma CO, Alejolowo OO, Olaolu T, Maimako RF, Suganuma K, Han Y, Kato K (2018) Metal nanoparticles restrict the growth of protozoan parasites. Artif Cells Nanomed Biotechnol 46:S86–s94

    Article  CAS  PubMed  Google Scholar 

  • Adeyemi OS, Murata Y, Sugi T, Han Y, Kato K (2019) Nanoparticles show potential to retard bradyzoites in vitro formation of Toxoplasma gondii. Folia Parasitol (Praha) 66

  • Alajmi RA, Al-Megrin WA, Metwally D, Al-Subaie H, Altamrah N, Barakat AM, Abdel Moneim AE, Al-Otaibi TT, El-Khadragy M (2019) Anti-Toxoplasma activity of silver nanoparticles green synthesized with Phoenix dactylifera and Ziziphus spina-christi extracts which inhibits inflammation through liver regulation of cytokines in Balb/c mice. Biosci Rep 39

  • Alday PH, Doggett JS (2017) Drugs in development for toxoplasmosis: advances, challenges, and current status. Drug Des Develop Therap 11:273–293

    Article  CAS  Google Scholar 

  • Aliberti J (2005) Host persistence: exploitation of anti-inflammatory pathways by Toxoplasma gondii. Nat Rev Immunol 5:162–170

    Article  CAS  PubMed  Google Scholar 

  • Azami SJ, Amani A, Keshavarz H, Najafi-Taher R, Mohebali M, Faramarzi MA, Mahmoudi M, Shojaee S (2018a) Nanoemulsion of atovaquone as a promising approach for treatment of acute and chronic toxoplasmosis. Eur J Pharm Sci Off J Eur Fed Pharm Sci 117:138–146

    CAS  Google Scholar 

  • Azami SJ, Teimouri A, Keshavarz H, Amani A, Esmaeili F, Hasanpour H, Elikaee S, Salehiniya H, Shojaee S (2018b) Curcumin nanoemulsion as a novel chemical for the treatment of acute and chronic toxoplasmosis in mice. Int J Nanomedicine 13:7363–7374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baggish AL, Hill DR (2002) Antiparasitic agent atovaquone. Antimicrob Agents Chemother 46:1163–1173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bahadar H, Maqbool F, Niaz K, Abdollahi M (2016) Toxicity of nanoparticles and an overview of current experimental models. Iran Biomed J 20:1–11

    PubMed  PubMed Central  Google Scholar 

  • Carlson C, Hussain SM, Schrand AM, Braydich-Stolle LK, Hess KL, Jones RL, Schlager JJ (2008) Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. J Phys Chem B 112:13608–13619

    Article  CAS  PubMed  Google Scholar 

  • Cern A, Connolly KL, Jerse AE, Barenholz Y (2018) In vitro susceptibility of Neisseria gonorrhoeae strains to mupirocin, an antibiotic reformulated for parenteral administration in nanoliposomes. Antimicrob Agents Chemother 62

  • Cowan MM (1999) Plant products as antimicrobial agents. Clin Microbiol Rev 12:564–582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dar MJ, McElroy CA, Khan MI, Satoskar AR, Khan GM (2020) Development and evaluation of novel miltefosine-polyphenol co-loaded second generation nano-transfersomes for the topical treatment of cutaneous leishmaniasis. Expert Opin Drug Del 17:97–110

    Article  CAS  Google Scholar 

  • Darade A, Pathak S, Sharma S, Patravale V (2018) Atovaquone oral bioavailability enhancement using electrospraying technology. Eur J Pharm Sci Off J Eur Fed Pharm Sci 111:195–204

    CAS  Google Scholar 

  • Dardé ML, Bouteille B, Pestre-Alexandre M (1992) Isoenzyme analysis of 35 Toxoplasma gondii isolates and the biological and epidemiological implications. J Parasitol 78:786–794

    Article  PubMed  Google Scholar 

  • De Marchi JGB, Jornada DS, Silva FK, Freitas AL, Fuentefria AM, Pohlmann AR, Guterres SS (2017) Triclosan resistance reversion by encapsulation in chitosan-coated-nanocapsule containing α-bisabolol as core: development of wound dressing. Int J Nanomedicine 12:7855–7868

    Article  PubMed  PubMed Central  Google Scholar 

  • Değerli K, Kilimcioğlu AA, Kurt O, Tamay AT, Ozbilgin A (2003) Efficacy of azithromycin in a murine toxoplasmosis model, employing a Toxoplasma gondii strain from Turkey. Acta Trop 88:45–50

    Article  PubMed  Google Scholar 

  • Esch GW (2010) Toxoplasmosis of animals and humans. J Parasitol 96:940–940

    Article  Google Scholar 

  • Etewa SE, El-Maaty DAA, Hamza RS, Metwaly AS, Sarhan MH, Abdel-Rahman SA, Fathy GM, El-Shafey MA (2018) Assessment of spiramycin-loaded chitosan nanoparticles treatment on acute and chronic toxoplasmosis in mice. J Parasit Dis 42:102–113

    Article  PubMed  Google Scholar 

  • Flegr J, Horáček J (2019) Negative effects of latent toxoplasmosis on mental health. Front Psych 10:1012

    Article  Google Scholar 

  • Flegr J, Prandota J, Sovickova M, Israili ZH (2014) Toxoplasmosis--a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PLoS One 9:e90203

    Article  PubMed  PubMed Central  Google Scholar 

  • Gaafar MR, Mady RF, Diab RG, Shalaby TI (2014) Chitosan and silver nanoparticles: promising anti-Toxoplasma agents. Exp Parasitol 143:30–38

    Article  CAS  PubMed  Google Scholar 

  • Ge L, Li Q, Wang M, Ouyang J, Li X, Xing MM (2014) Nanosilver particles in medical applications: synthesis, performance, and toxicity. Int J Nanomedicine 9:2399–2407

    PubMed  PubMed Central  Google Scholar 

  • Goy R, Britto DD, Assis O (2009) A review of the antimicrobial activity of chitosan. Polimeros: Ciencia et Tecnologia 19(3):241–247

    Article  CAS  Google Scholar 

  • Hagras NA, Allam AF, Farag HF, Osman MM, Shalaby TI, Fawzy Hussein Mogahed NM, Tolba MM, Shehab AY (2019) Successful treatment of acute experimental toxoplasmosis by spiramycin-loaded chitosan nanoparticles. Exp Parasitol 204:107717

    Article  CAS  PubMed  Google Scholar 

  • Hill D, Dubey JP (2002) Toxoplasma gondii: transmission, diagnosis and prevention. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 8:634–640

    CAS  Google Scholar 

  • Hill DE, Dubey JP (2016) Toxoplasma gondii as a parasite in food: analysis and control. Microbiol Spectr 4

  • Hsin YH, Chen CF, Huang S, Shih TS, Lai PS, Chueh PJ (2008) The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells. Toxicol Lett 179:130–139

    Article  CAS  PubMed  Google Scholar 

  • Jaiswal M, Dudhe R, Sharma PK (2015) Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech 5:123–127

    Article  PubMed  Google Scholar 

  • Jin X, Li M, Wang J, Marambio-Jones C, Peng F, Huang X, Damoiseaux R, Hoek EM (2010) High-throughput screening of silver nanoparticle stability and bacterial inactivation in aquatic media: influence of specific ions. Environ Sci Technol 44:7321–7328

    Article  CAS  PubMed  Google Scholar 

  • Jones JL, Kruszon-Moran D, Sanders-Lewis K, Wilson M (2007) Toxoplasma gondii infection in the United States, 1999 2004, decline from the prior decade. Am J Trop Med Hyg 77:405–410

    Article  PubMed  Google Scholar 

  • Keyhani A, Ziaali N, Shakibaie M, Kareshk AT, Shojaee S, Asadi-Shekaari M, Sepahvand M, Mahmoudvand H (2020) Biogenic selenium nanoparticles target chronic toxoplasmosis with minimal cytotoxicity in a mouse model. J Med Microbiol 69:104–110

    Article  CAS  PubMed  Google Scholar 

  • Khosravi M, Mohammad Rahimi H, Doroud D, Mirsamadi ES, Mirjalali H, Zali MR (2020) In vitro evaluation of mannosylated paromomycin-loaded solid lipid nanoparticles on acute toxoplasmosis. Front Cell Infect Microbiol 10:33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koide T, Nose M, Ogihara Y, Yabu Y, Ohta N (2002) Leishmanicidal effect of curcumin in vitro. Biol Pharm Bull 25:131–133

    Article  CAS  PubMed  Google Scholar 

  • Kone BC, Kaleta M, Gullans SR (1988) Silver ion (Ag+)-induced increases in cell membrane K+ and Na+ permeability in the renal proximal tubule: reversal by thiol reagents. J Membr Biol 102:11–19

    Article  CAS  PubMed  Google Scholar 

  • Korani M, Ghazizadeh E, Korani S, Hami Z, Mohammadi-Bardbori A (2015) Effects of silver nanoparticles on human health. Eur J Nanomedicine 7:51–62

    Article  CAS  Google Scholar 

  • Kur J, Holec-Gasior L, Hiszczyńska-Sawicka E (2009) Current status of toxoplasmosis vaccine development. Expert Rev Vaccines 8:791–808

    Article  CAS  PubMed  Google Scholar 

  • Machado LF, Sanfelice RA, Bosqui LR, Assolini JP, Scandorieiro S, Navarro IT, Depieri Cataneo AH, Wowk PF, Nakazato G, Bordignon J, Pavanelli WR, Conchon-Costa I, Costa IN (2020) Biogenic silver nanoparticles reduce adherence, infection, and proliferation of Toxoplasma gondii RH strain in HeLa cells without inflammatory mediators induction. Exp Parasitol 211:107853

    Article  CAS  PubMed  Google Scholar 

  • Mcauley JB, Jones JL, Singh K (2015) Toxoplasma. In: Manual of clinical microbiology, 11th edn. American Society of Microbiology, Washington, DC, pp 2373–2386

    Chapter  Google Scholar 

  • McLeod R, Khan AR, Noble GA, Latkany P, Jalbrzikowski J, Boyer K (2006) Severe sulfadiazine hypersensitivity in a child with reactivated congenital toxoplasmic chorioretinitis. Pediatr Infect Dis J 25:270–272

    Article  PubMed  Google Scholar 

  • Melchor SJ, Ewald SE (2019) Disease tolerance in Toxoplasma infection. Front Cell Infect Microbiol 6(9):185

    Article  Google Scholar 

  • Mohammad Rahimi H, Khosravi M, Hesari Z, Sharifdini M, Mirjalali H, Zali MR (2020) Anti-Toxoplasma activity and chemical compositions of aquatic extract of Mentha pulegium L. and Rubus idaeus L.: an in vitro study. Food Sci Nutr 8:3656–3664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montoya JG, Liesenfeld O (2004) Toxoplasmosis. Lancet 363:1965–1976

    Article  CAS  PubMed  Google Scholar 

  • Montoya JG, Remington JS (1996) Toxoplasmic chorioretinitis in the setting of acute acquired toxoplasmosis. Clin Infect Dis 23:277–282

    Article  CAS  PubMed  Google Scholar 

  • Montoya JG, Remington JS (2008) Management of Toxoplasma gondii infection during pregnancy. Clin Infect Dis 47:554–566

    Article  PubMed  Google Scholar 

  • Nafari A, Cheraghipour K, Sepahvand M, Shahrokhi G, Gabal E, Mahmoudvand H (2020) Nanoparticles: new agents toward treatment of leishmaniasis. Parasite Epidemiol Control 10:e00156

    Article  PubMed  PubMed Central  Google Scholar 

  • Pissuwan D, Valenzuela SM, Miller CM, Cortie MB (2007) A golden bullet? Selective targeting of Toxoplasma gondii tachyzoites using antibody-functionalized gold nanorods. Nano Lett 7:3808–3812

    Article  CAS  PubMed  Google Scholar 

  • Rahman K, Khan SU, Fahad S, Chang MX, Abbas A, Khan WU, Rahman L, Haq ZU, Nabi G, Khan D (2019) Nano-biotechnology: a new approach to treat and prevent malaria. Int J Nanomedicine 14:1401–1410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Randhawa MA, Gondal MA, Al-Zahrani AH, Rashid SG, Ali A (2015) Synthesis, morphology and antifungal activity of nano-particulated amphotericin-B, ketoconazole and thymoquinone against Candida albicans yeasts and Candida biofilm. J Environ Sci Health A Tox Hazard Subst Environ Eng 50:119–124

    Article  CAS  PubMed  Google Scholar 

  • Schöler N, Krause K, Kayser O, Müller RH, Borner K, Hahn H, Liesenfeld O (2001) Atovaquone nanosuspensions show excellent therapeutic effect in a new murine model of reactivated toxoplasmosis. Antimicrob Agents Chemother 45:1771–1779

    Article  PubMed  PubMed Central  Google Scholar 

  • Sepulveda-Arias JC, Veloza LA, Mantilla-Muriel LE (2014) Anti-Toxoplasma activity of natural products: a review. Recent Pat Antiinfect Drug Discov 9:186–194

    Article  CAS  PubMed  Google Scholar 

  • Shojaee S, Firouzeh N, Keshavarz H, Jafar-Pour Azami S, Salimi M, Mohebali M (2019) Nanosilver colloid inhibits Toxoplasma gondii tachyzoites and bradyzoites in vitro. Iran J Parasitol 14:362–367

    PubMed  PubMed Central  Google Scholar 

  • Shubar HM, Lachenmaier S, Heimesaat MM, Lohman U, Mauludin R, Mueller RH, Fitzner R, Borner K, Liesenfeld O (2011) SDS-coated atovaquone nanosuspensions show improved therapeutic efficacy against experimental acquired and reactivated toxoplasmosis by improving passage of gastrointestinal and blood-brain barriers. J Drug Target 19:114–124

    Article  CAS  PubMed  Google Scholar 

  • Spann MN, Sourander A, Surcel HM, Hinkka-Yli-Salomäki S, Brown AS (2017) Prenatal toxoplasmosis antibody and childhood autism. Autism Res Off J Int Soc Autism Res 10:769–777

    Article  Google Scholar 

  • Sun Y, Chen D, Pan Y, Qu W, Hao H, Wang X, Liu Z, Xie S (2019) Nanoparticles for antiparasitic drug delivery. Drug Deliv 26:1206–1221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Surender V, Deepika M (2016) Solid lipid nanoparticles: a comprehensive review. J Chem Pharm Res 8:102–114

    CAS  Google Scholar 

  • Teimouri A, Azami SJ, Keshavarz H, Esmaeili F, Alimi R, Mavi SA, Shojaee S (2018) Anti-Toxoplasma activity of various molecular weights and concentrations of chitosan nanoparticles on tachyzoites of RH strain. Int J Nanomedicine 13:1341–1351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Torgerson PR, Mastroiacovo P (2013) The global burden of congenital toxoplasmosis: a systematic review. Bull World Health Organ 91:501–508

    Article  PubMed  PubMed Central  Google Scholar 

  • Vergara-Duque D, Cifuentes-Yepes L, Hincapie-Riaño T, Clavijo-Acosta F, Juez-Castillo G, Valencia-Vidal B (2020) Effect of silver nanoparticles on the morphology of Toxoplasma gondii and Salmonella braenderup. J Nanotech 2020

  • Wang JJ, Zeng ZW, Xiao RZ, Xie T, Zhou GL, Zhan XR, Wang SL (2011) Recent advances of chitosan nanoparticles as drug carriers. Int J Nanomedicine 6:765–774

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yadollahi R, Vasilev K, Simovic S (2015) Nanosuspension technologies for delivery of poorly soluble drugs. J Nanomaterial 2015

  • Yallapu MM, Nagesh PK, Jaggi M, Chauhan SC (2015) Therapeutic applications of curcumin nanoformulations. AAPS J 17:1341–1356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank all members of the Foodborne and Waterborne Diseases Research Center for their supports.

Funding

None.

Author information

Authors and Affiliations

  1. Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sanaz Jafarpour Azami, Hanieh Mohammad Rahimi & Hamed Mirjalali

  2. Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Sanaz Jafarpour Azami

  3. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Reza Zali

Authors
  1. Sanaz Jafarpour Azami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hanieh Mohammad Rahimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hamed Mirjalali
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohammad Reza Zali
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceived the paper: HM. Data gathering and analysing: SJA HMR. Data validation: HM SJA MRZ. Wrote the paper: SJA. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Hamed Mirjalali.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

All procedures performed in this study were in accordance with the ethical standards (IR.SBMU.RIGLD.REC.1398.034) released by the Ethical Review Committee of the Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jafarpour Azami, S., Mohammad Rahimi, H., Mirjalali, H. et al. Unravelling Toxoplasma treatment: conventional drugs toward nanomedicine. World J Microbiol Biotechnol 37, 48 (2021). https://doi.org/10.1007/s11274-021-03000-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11274-021-03000-x

Keywords

Search

Navigation