Iranian Journal of Allergy, Asthma and Immunology 2017. 16(3):271-281.

Intravenous Injection of Myelin Oligodendrocyte Glycoprotein-coated PLGA Microparticles Have Tolerogenic Effects in Experimental Autoimmune Encephalomyelitis
Mehrdad Gholamzad, Masoumeh Ebtekar, Mehdi Shafiee Ardestani

Abstract


The abnormal function of the T lymphocytes causes a range of autoimmune diseases, particularly multiple sclerosis; hence, several methods have been used to treat these disorders through the induction of antigen-specific tolerance in T cells. The present study aims to use a simple and low-cost method to produce poly (lactic-co-glycolic acid) (PLGA) nanoparticles for carrying antigens and inducing antigen-specific tolerance. In this study, PLGA nanoparticles were produced using the water/oil/water (W/O/W) method. The myelin oligodendrocyte glycoprotein (MOG) peptide and ovalbumin peptide(OVA) were covalently bound to the synthetic PLGA nanoparticles in the presence of 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDCI) and were injected to six groups of C57BL/6 mice one week before the induction of the experimental autoimmune encephalomyelitis (EAE) intravenously or subcutaneously; one group was considered as control; finally, immunologic responses including delayed-type hypersensitivity (DTH) response and lymphocyte proliferation were investigated. The results showed that the intravenous injection of microparticles containing MOG peptides before the development of the EAE model, not only could delay the incidence of syndrome, but also increase the antigen-specific tolerance. Moreover, a reduced delayed-type hypersensitivity response was observed in the mice primed with microparticles containing MOG peptides. In addition, a reduced spleen lymphocyte proliferation was found in the same mice when challenged with antigens. The present study proposes a simple, inexpensive, effective and safe method for preparing MOG-conjugated PLGA microparticles with immune tolerance properties that can be used in the treatment or reducing clinical syndromes of EAE model.


Keywords


Experimental autoimmune encephalomyelitis; Immune tolerance; Microparticles; poly (Lactic-co-glycolic acid)

Full Text:

PDF

References


1. Jacobson DL, Gange SJ, Rose NR, Graham NM. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol 1997; 84(3):223-43.

2. Hillaireau H, Couvreur P. Nanocarriers’ entry into the cell: relevance to drug delivery. Cell Mol Life Sci 2009; 66(17):2873-96.

3. Sospedra M, Martin R. Immunology of multiple sclerosis. Annu Rev Immunol 2005; 23:683-747.

4. Legoux FP, Lim J-B, Cauley AW, Dikiy S, Ertelt J, Mariani TJ, et al. CD4+ T cell tolerance to tissue-restricted self antigens is mediated by antigen-specific regulatory T cells rather than deletion. Immunity 2015; 43(5):896-908.

5. Fabienne Danhier , Eduardo Ansorena , Joana M. Silva , et al. PLGA-based nanoparticles: An overview of biomedical applications. Journal of Controlled Release2012;(161): 505–522

6. Kumari A, Yadav SK, Pakade YB, Singh B, Yadav SC. Development of biodegradable nanoparticles for delivery of quercetin. Colloids Surf B Biointerfaces 2010; 80(2):184-92.

7. Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids and Surfaces B: Biointerfaces 2010;75(1):1-18.

8. Prokop A, Davidson JM. Nanovehicular intracellular delivery systems. J Pharm Sci 2008; 97(9):3518-90.

9. Vert M, Mauduit J, Li S. Biodegradation of PLA/GA polymers: increasing complexity. Biomaterials 1994; 15(15):1209-13.

10. des Rieux A, Fievez V, Garinot M, Schneider Y-J, Préat V. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J Control Release 2006; 116(1):1-27.

11. Keijzer C, Slutter B, Van Der Zee R, Jiskoot W, Van Eden W, Broere F. PLGA, PLGA-TMC and TMC-TPP nanoparticles differentially modulate the outcome of nasal vaccination by inducing tolerance or enhancing humoral immunity. PLoS One 2011; 6(11):e26684.

12. Yeste A, Nadeau M, Burns EJ, Weiner HL, Quintana FJ. Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 2012; 109(28):11270-5.

13. Makadia HK, Siegel SJ. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers 2011; 3(3):1377-97.

14. Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V. PLGA-based nanoparticles: an overview of biomedical applications. J Control Release 2012; 161(2):505-22.

15. Saini V, Jain V, Sudheesh M, Jaganathan K, Murthy P, Kohli D. Comparison of humoral and cell-mediated immune responses to cationic PLGA microspheres containing recombinant hepatitis B antigen. Int J Pharm 2011; 408(1):50-7.

16. Gaumet M, Vargas A, Gurny R, Delie F. Nanoparticles for drug delivery: the need for precision in reporting particle size parameters. Eur J Pharm Biopharm 2008; 69(1):1-9.

17. Getts DR, Turley DM, Smith CE, Harp CT, McCarthy D, Feeney EM, et al. Tolerance induced by apoptotic antigen-coupled leukocytes is induced by PD-L1+ and IL-10–producing splenic macrophages and maintained by T regulatory cells. J Immunol 2011; 187(5):2405-17.

18. Ghaffarinia A, Parvaneh S, Jalili C, Riazi-Rad F, Yaslianifard S, Pakravan N. Immunomodulatory Effect of Chymotrypsin in CNS Is Sex-independent: Evidence of Anti-inflammatory Role for IL-17 in EAE. Iran J Allergy Asthma Immunol 2016; 15(2):145-55.

19. Getts DR, Martin AJ, McCarthy DP, Terry RL, Hunter ZN, Yap WT, et al. Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis. Nat Biotechnol 2012; 30(12):1217-24.

20. Foged C, Brodin B, Frokjaer S, Sundblad A. Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model. Int J Pharm 2005; 298(2):315-22.

21. Protective AVNVI, Champion CI, Kickhoefer VA, Liu G, Moniz RJ, Freed AS, et al. A vault nanoparticle vaccine induces protective mucosal immunity. PLoS One 2009; 4(4):e5409.

22. Getts DR, Martin AJ, McCarthy DP, Terry RL, Hunter ZN, Yap WT, et al. Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis. Nat Biotechnol 2012; 30(12):1217-24.

23. Fonseca C, Simoes S, Gaspar R. Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J Control Release 2002; 83(2):273-86.

24. Derakhshandeh K, Erfan M, Dadashzadeh S. Encapsulation of 9-nitrocamptothecin, a novel anticancer drug, in biodegradable nanoparticles: factorial design, characterization and release kinetics. Eur J Pharm Biopharm 2007; 66(1):34-41.

25. Chatenoud L, Primo J, Bach J-F. CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice. J Immunol 1997; 158(6):2947-54.

26. Chatenoud L, Thervet E, Primo J, Bach J-F. Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc Natl Acad Sci U S A 1994; 91(1):123-7.

27. Maldonado RA, LaMothe RA, Ferrari JD, Zhang A-H, Rossi RJ, Kolte PN, et al. Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance. Proc Natl Acad Sci U S A 2015; 112(2):E156-65.


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.