Skip to main content

Advertisement

SpringerLink
Log in

Advancing drug delivery systems for the treatment of multiple sclerosis

  • AUTOIMMUNITY
  • Published:
Immunologic Research Aims and scope Submit manuscript

An Erratum to this article was published on 19 February 2016

Abstract

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood–brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the inflammatory response. There are currently 10 DMTs approved for the relapsing forms of MS; these vary with regard to their efficacy, route and frequency of administration, adverse effects, and toxicity profile. Better drug delivery systems are being developed in order to decrease adverse effects, increase drug efficacy, and increase patient compliance through the direct targeting of pathologic cells. Here, we address the uses and benefits of advanced drug delivery systems, including nanoparticles, microparticles, fusion antibodies, and liposomal formulations. By altering the properties of therapeutic particles and enhancing targeting, breakthrough drug delivery technologies potentially applicable to multiple disease treatments may rapidly emerge.

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
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Wingerchuk DM, Carter JL. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc. 2014;89:225–40.

    Article  PubMed  Google Scholar 

  2. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998;338:278–85.

    Article  CAS  PubMed  Google Scholar 

  3. Alonso A, Hernán MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology. 2008;71:129–35.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Files DK, Jausurawong T, Katrajian T, Danoff R. Multiple sclerosis. Prim Care Clin Off Pract. 2015;42:159–72.

    Article  Google Scholar 

  5. Kamm CP, Uitdehaag BM, Polman CH. Multiple sclerosis: current knowledge and future outlook. Eur Neurol. 2014;72:132–41.

    Article  CAS  PubMed  Google Scholar 

  6. Prat E, Tomaru U, Sabater L, Park D, Granger R, Kruse N, Ohayon J, et al. HLA-DRB5*0101 and -DRB1*1501 expression in the multiple sclerosis-associated HLA-DR15 haplotype. J Neuroimmunol. 2005;167:108–19.

    Article  CAS  PubMed  Google Scholar 

  7. Kaushansky N, Altmann DM, Ascough S, David CS, Lassmann H, Ben-Nun A. HLA-DQB1*0602 determines disease susceptibility in a new “humanized” multiple sclerosis model in HLA-DR15 (DRB1*1501;DQB1*0602) transgenic mice. J Immunol. 2009;183:3531–41.

    Article  CAS  PubMed  Google Scholar 

  8. Calabresi PA. Diagnosis and management of multiple sclerosis. Am Fam Physician. 2004;70:1935–44.

    PubMed  Google Scholar 

  9. Dhib-Jalbut S, Marks S. Interferon-β mechanisms of action in multiple sclerosis. Neurology. 2010;74:S17–24.

    Article  CAS  PubMed  Google Scholar 

  10. Khan O, Dhib-Jalbut S. Neutralizing antibodies to interferon β-1a and interferon β-1b in MS patients are cross-reactive. Neurology. 1998;51:1698–702.

    Article  CAS  PubMed  Google Scholar 

  11. Wingerchuk D. Multiple sclerosis disease-modifying therapies: adverse effect surveillance and management. Expert Rev Neurother. 2006;6:333–46.

    Article  CAS  PubMed  Google Scholar 

  12. Lalive PH, Neuhaus O, Benkhoucha M, Burger D, Hohlfeld R, Zamvil SS, Weber MS. Glatiramer acetate in the treatment of multiple sclerosis: emerging concepts regarding its mechanism of action. CNS Drugs. 2011;25:401–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Aharoni R, Arnon R. Enhanced myelination in autoimmunity and in normal development induced by glatiramer acetate. Isr Med Assoc J. 2014;16:611–3.

    PubMed  Google Scholar 

  14. Arnon R, Sela M. Immunomodulation by the copolymer glatiramer acetate. J Mol Recognit. 2003;16:412–21.

    Article  CAS  PubMed  Google Scholar 

  15. Karussia D, Teitelnaum D, Sicsic C, Brenner T. Long-term treatment of multiple sclerosis with glatiramer acetate: natural history of the subtypes of anti-glatiramer acetate antibodies and their correlation with clinical efficacy. J Neuroimmunol. 2010;220:125–30.

    Article  Google Scholar 

  16. Cohen J, Chun J. Mechanisms of fingolimod’s efficacy and adverse effects in multiple sclerosis. Ann Neurol. 2011;69:759–77.

    Article  CAS  PubMed  Google Scholar 

  17. Claussen M, Korn T. Immune mechanisms of new therapeutic strategies in MS: teriflunomide. Clin Immunol. 2012;142:49–56.

    Article  CAS  PubMed  Google Scholar 

  18. Bomprezzi R. Dimethyl fumarate in the treatment of relapsing–remitting multiple sclerosis: an overview. Ther Adv Neurol Disord. 2015;8:20–30.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Linker R, Gold R. Dimethyl fumarate for treatment of multiple sclerosis: mechanism of action, effectiveness, and side effects. Curr Neurol Neursci Rep. 2013;13:394.

    Article  Google Scholar 

  20. Burton JM, O’Connor PW, Hohol M, Beyene J. Oral versus intravenous steroids for treatment of relapses in multiple sclerosis. Cochrane Database Syst Rev. 2009;3:CD006921.

    PubMed  Google Scholar 

  21. Gaillard PJ, Appeldoorn CCM, Rip J, Dorland R, Van Der Pol SMA, Kooij G, Vries HE, Reijerkerk A. Enhanced brain delivery of liposomal methylprednisolone improved therapeutic efficacy in a model of neuroinflammation. J Control Release. 2012;164:364–9.

    Article  CAS  PubMed  Google Scholar 

  22. Ransohoff R. Natalizumab for multiple sclerosis. N Engl J Med. 2007;356:2622–9.

    Article  CAS  PubMed  Google Scholar 

  23. He D, Guo R, Zhang F, Zhang C, Dong S, Zhou H. Rituximab for relapsing–remitting multiple sclerosis. Cochrane Database Syst Rev. 2013;12:009130.

    Google Scholar 

  24. Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH. B-cell depletion with rituximab in relapsing–remitting multiple sclerosis. N Engl J Med. 2008;358:676–88.

    Article  CAS  PubMed  Google Scholar 

  25. Klein C, Lammens A, Schäfer W, Georges G, Schwaiger M, Mössner E, Hopfner KP, et al. Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties. MAbs. 2013;5:22–33.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Jean GW, Comeau JM. Role of obinutuzumab in the treatment of chronic lymphocytic leukemia. Am J Health Syst Pharm. 2015;72:933–42.

    Article  CAS  PubMed  Google Scholar 

  27. English C, Aloi JJ. New FDA-approved disease-modifying therapies for multiple sclerosis. Clin Ther. 2015;37:691–715.

    Article  CAS  PubMed  Google Scholar 

  28. Cossburn M, Pace AA, Jones J, Ali R, Ingram G, Baker K, Hirst C, et al. Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort. Neurology. 2011;77:573–9.

    Article  CAS  PubMed  Google Scholar 

  29. Le Deley ML, Suzan F, Cutuli B, Delaloge S, Shamsaldin A, Linassier C, Clisant S, et al. Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony-stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer. J Clin Oncol. 2007;25:292–300.

    Article  CAS  PubMed  Google Scholar 

  30. Scott LJ, Figgitt DP. Mitoxantrone: a review of its use in multiple sclerosis. CNS Drugs. 2004;18:379–96.

    Article  CAS  PubMed  Google Scholar 

  31. Todaro M, Zeuner A, Stassi G. Role of apoptosis in autoimmunity. J Clin Immunol. 2004;24:1–11.

    Article  CAS  PubMed  Google Scholar 

  32. Pender MP, Rist MJ. Apoptosis of inflammatory cells in immune control of the nervous system: role of glia. Glia. 2001;36:137–44.

    Article  CAS  PubMed  Google Scholar 

  33. Hebb ALO, Moore CS, Bhan V, Robertson GS. Targeting apoptosis to treat multiple sclerosis. Curr Drug Discov Technol. 2008;5:75–7.

    Article  CAS  PubMed  Google Scholar 

  34. Wosik K, Antel J, Kuhlmann T, Brück W, Massie B, Nalbantoglu J. Oligodendrocyte injury in multiple sclerosis: a role for p53. J Neurochem. 2003;85:635–44.

    Article  CAS  PubMed  Google Scholar 

  35. Sharief MK, Noori MA, Zoukos Y. Reduced expression of the inhibitor of apoptosis proteins in T cells from patients with multiple sclerosis following interferon-beta therapy. J Neuroimmunol. 2002;129:224–31.

    Article  CAS  PubMed  Google Scholar 

  36. Zehntner SP, Bourbonnière L, Moore CS, Morris SJ, Methot D, St Jean M, Lacasse E, et al. X-linked inhibitor of apoptosis regulates T cell effector function. J Immunol. 2007;179:7553–60.

    Article  CAS  PubMed  Google Scholar 

  37. Zhang Z, Tongchusak S, Mizukami Y, Kang YJ, Ioji T, Touma M, Reinhold B, et al. Induction of anti-tumor cytotoxic T cell responses through PLGA-nanoparticle mediated antigen delivery. Biomaterials. 2011;32:3666–78.

    Article  CAS  PubMed  Google Scholar 

  38. Lewis JS, Zaveri TD, Crooks CP, Keselowsky BG. Microparticle surface modifications targeting dendritic cells for non-activating applications. Biomaterials. 2012;33:7221–32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Lu CH, Willner B, Willner I. DNA nanotechnology: from sensing and DNA machines to drug-delivery systems. ACS Nano. 2013;7:8320–32.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Tsai M, Lu Z, Wientjes MG, Au JLS. Paclitaxel-loaded polymeric microparticles: quantitative relationships between in vitro drug release rate and in vivo pharmacodynamics. J Control Release. 2013;172:737–44.

    Article  CAS  PubMed  Google Scholar 

  42. Youan B, Benoit M, Baras B, Gillard J. Protein-loaded poly(epsilon-caprolactone) microparticles. I. Optimization of the preparation by (water-in-oil)-in water emulsion solvent evaporation. J Microencapsul. 1999;16:587–99.

    Article  CAS  PubMed  Google Scholar 

  43. Jones SA, Martin GP, Brown MB. Manipulation of beclomethasone–hydrofluoroalkane interactions using biocompatible macromolecules. J Pharm Sci. 2006;95:1060–74.

    Article  CAS  PubMed  Google Scholar 

  44. Grizzi I, Garreau H, Li S, Vert M. Hydrolytic degradation of devices based on poly(DL-lactic acid) size dependence. Biomaterials. 1995;16:305–11.

    Article  CAS  PubMed  Google Scholar 

  45. Kim SE, Park JH, Cho YW, Chung H, Jeong SY, Lee EB, Kwon IC. Porous chitosan scaffold containing microspheres loaded with transforming growth factor-β1: implications for cartilage tissue engineering. J Control Release. 2003;91:365–74.

    Article  CAS  PubMed  Google Scholar 

  46. Holland TA, Tabata Y, Mikos AG. In vitro release of transforming growth factor-β1 from gelatin microparticles encapsulated in biodegradable, injectable oligo(poly(ethylene glycol) fumarate) hydrogels. J Control Release. 2003;91:299–313.

    Article  CAS  PubMed  Google Scholar 

  47. Berthold A, Cremer K, Kreuter J. Collagen microparticles: carriers for glucocorticosteroids. Eur J Pharm Biopharm. 1998;45:23–9.

    Article  CAS  PubMed  Google Scholar 

  48. Bowersock TL, HogenEsch H, Suckow M, Porter RE, Jackson R, Park H, Park K. Oral vaccination with alginate microsphere systems. J Control Release. 1996;39:209–20.

    Article  CAS  Google Scholar 

  49. Yuan L, Tang Q, Yang D, Zhang JZ, Zhang F, Hu J. Preparation of pH-responsive mesoporous silica nanoparticles and their application in controlled drug delivery. J Phys Chem C. 2011;115:9926–32.

    Article  CAS  Google Scholar 

  50. Wei G, Pettway GJ, McCauley LK, Ma PX. The release profiles and bioactivity of parathyroid hormone from poly (lactic-co-glycolic acid) microspheres. Biomaterials. 2004;25:345–52.

    Article  CAS  PubMed  Google Scholar 

  51. Wischke C, Schwendeman S. Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles. Int J Pharm. 2008;364:298–327.

    Article  CAS  PubMed  Google Scholar 

  52. Stephan MT, Moon JJ, Um SH, Bershteyn A, Irvine DJ. Therapeutic cell engineering with surface-conjugated synthetic nanoparticles. Nat Med. 2010;16:1035–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Hubbell JA, Thomas SN, Swartz MA. Materials engineering for immunomodulation. Nature. 2009;462:449–60.

    Article  CAS  PubMed  Google Scholar 

  54. Ihler GM, Glew RH, Schnure FW. Enzyme loading of erythrocytes. Proc Natl Acad Sci USA. 1973;70:2663–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Steinman RM, Gutchinov B, Witmer MD, Nussenzweig MC. Dendritic cells are the principal stimulators of the primary mixed leukocyte reaction in mice. J Exp Med. 1983;157:613–27.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Petzold C, Schallenberg S, Stern JNH, Kretschmer K. Targeted antigen delivery to DEC-205+ dendritic cells for tolerogenic vaccination. Rev Diabet Stud. 2012;9:305–18.

    Article  PubMed Central  PubMed  Google Scholar 

  57. Stern JNH, Keskin DB, Kato Z, Waldner H, Schallenberg S, Anderson A, von Boehmer H, et al. Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells. Proc Natl Acad Sci USA. 2010;107:17280–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Serafini B, Columba-Cabezas S, Di Risa F, Aloisi F. Intracerebral recruitment and maturation of dendritic cells in the onset and progression of experimental autoimmune encephalomyelitis. Am J Pathol. 2000;157:1991–2002.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Izikson L. Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR) 2. J Exp Med. 2000;192:1075–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Greter M, Heppner F, Lemos M, Odermatt B, Goebels N, Laufer T, Noelle R, et al. Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med. 2005;11:328–34.

    Article  CAS  PubMed  Google Scholar 

  61. McMenamin P. Distribution and phenotype of dendritic cells and resident tissue macrophages in the dura mater, leptomeninges, and choroid plexus of the rat brain as demonstrated in wholemount preparations. J Comp Neurol. 1999;405:553–62.

    Article  CAS  PubMed  Google Scholar 

  62. Bailey S, Schreiner B, McMahon E, Miller S. CNS myeloid DCs presenting endogenous myelin peptides “preferentially” polarize CD4+ T(H)-17 cells in relapsing EAE. Nat Immunol. 2007;8:172–80.

    Article  CAS  PubMed  Google Scholar 

  63. Lande R. Plasmacytoid dendritic cells in multiple sclerosis: intracerebral recruitment and impaired maturation in response to interferon-beta. J Neuropathol Exp Neurol. 2008;67:388–401.

    Article  CAS  PubMed  Google Scholar 

  64. Gottfried-Blackmore A, Krauzner U, Idoyaga J, Felger J, McEwen B, Bulloch K. Acute in vivo exposure to interferon-gamma enables resident brain dendritic cells to become effective antigen presenting cells. Proc Natl Acad Sci USA. 2009;106:20918–23.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Cao Y, Goods B, Raddassi K, Nepom G, Kwok W, Love J, Hafler D. Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis. Sci Transl Med. 2015;7:287ra74.

    Article  PubMed  Google Scholar 

  66. Bettelli E, Sullivan B, Szabo SJ, Sobel RA, Glimcher LH, Kuchroo VK. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J Exp Med. 2004;200:79–87.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol. 2009;27:485–517.

    Article  CAS  PubMed  Google Scholar 

  68. Ghoreschi K, Laurence A, Yang X-P, Tato CM, McGeachy MJ, Konkel JE, Ramos HL, et al. Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling. Nature. 2010;467:967–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Janeway C, Travers J, Walport M, Shlomchik M. The production of armed effector T cells. In: Immunobiology: the immune system in health and disease. 5th ed. New York: Garland Science; 2001. ISBN-10: 0-8153-3642-X.

  70. Kool M, Soullié T, van Nimwegen M, Willart MAM, Muskens F, Jung S, Hoogsteden HC, et al. Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J Exp Med. 2008;205:869–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Sharp FA, Ruane D, Claass B, Creagh E, Harris J, Malyala P, Singh M, et al. Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome. Proc Natl Acad Sci USA. 2009;106:870–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Kato M, McDonald KJ, Khan S, Ross IL, Vuckovic S, Chen K, Munster D, et al. Expression of human DEC-205 (CD205) multilectin receptor on leukocytes. Int Immunol. 2006;18:857–69.

    Article  CAS  PubMed  Google Scholar 

  73. Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J Exp Med. 2002;196:1627–38.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Champion JA, Walker A, Mitragotri S. Role of particle size in phagocytosis of polymeric microspheres. Pharm Res. 2008;25:1815–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Tran K, Shen H. The role of phagosomal pH on the size-dependent efficiency of cross-presentation by dendritic cells. Biomaterials. 2009;30:1356–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Reddy ST, van der Vlies AJ, Simeoni E, O’Neil CP, Swartz MA, Hubbell JA. Exploiting lymphatic transport and complement activation in nanoparticle vaccines. Nat Biotechnol. 2007;25:1159–64.

    Article  CAS  PubMed  Google Scholar 

  77. Reddy ST, Rehor A, Schmoekel HG, Hubbell JA, Swartz MA. In vivo targeting of dendritic cells in lymph nodes with poly (propylene sulfide) nanoparticles. J Control Release. 2006;112:26–34.

    Article  CAS  PubMed  Google Scholar 

  78. Idoyaga J, Fiorese C, Zbytnuik L, Lubkin A, Miller J, Malissen B, Mucida D, et al. Specialized role of migratory dendritic cells in peripheral tolerance induction. J Clin Invest. 2013;123:844–54.

    PubMed Central  CAS  PubMed  Google Scholar 

  79. Jones A, Opejin A, Henderson JG, Gross C, Jain R, Epstein JA, Flavell RA, et al. Peripherally induced tolerance depends on peripheral regulatory T cells that require Hopx to inhibit intrinsic IL-2 expression. J Immunol. 2015;195:1489–97.

    Article  CAS  PubMed  Google Scholar 

  80. Hawiger D, Masilamani RF, Bettelli E, Kuchroo VK, Nussenzweig MC. Immunological unresponsiveness characterized by increased expression of CD5 on peripheral T cells induced by dendritic cells in vivo. Immunity. 2004;20:695–705.

    Article  CAS  PubMed  Google Scholar 

  81. Nussenzweig MC, Steinman RM, Witmer MD, Gutchinov B. A monoclonal antibody specific for mouse dendritic cells. Proc Natl Acad Sci USA. 1982;79:161–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  82. Kasahara S, Clark EA. Dendritic cell-associated lectin 2 (DCAL2) defines a distinct CD8α- dendritic cell subset. J Leukoc Biol. 2012;2012(91):437–48.

    Article  Google Scholar 

  83. Dudziak D, Kamphorst AO, Heidkamp GF, Buchholz VR, Trumpfheller C, Yamazaki S, Cheong C, et al. Differential antigen processing by dendritic cell subsets in vivo. Science. 2007;315:107–11.

    Article  CAS  PubMed  Google Scholar 

  84. Nagae M, Yamanaka K, Hanashima S, Ikeda A, Morita-Matsumoto K, Satoh T, Matsumoto N, et al. Recognition of bisecting N-acetylglucosamine: structural basis for asymmetric interaction with the mouse lectin dendritic cell inhibitory receptor 2. J Biol Chem. 2013;288:33598–610.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  85. Yamazaki S, Dudziak D, Heidkamp GF, Fiorese C, Bonito AJ, Inaba K, Nussenzweig MC, et al. CD8+ CD205+ splenic dendritic cells are specialized to induce Foxp3+ regulatory T cells. J Immunol. 2008;181:6923–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  86. Yamazaki S, Dudziak D, Heidkamp GF, Fiorese C, Bonito AJ, Inaba K, Nussenzweig MC, et al. DCIR2+ cDC2 DCs and Zbtb32 restore CD4+ T cell tolerance and inhibit diabetes. Diabetes. 2015;64:3521–31.

    Article  Google Scholar 

  87. Hunter Z, McCarthy D, Yap W, Harp C, Getts D, Shea L, Miller S. A biodegradable nanoparticle platform for the induction of antigen-specific immune tolerance for treatment of autoimmune disease. ACS Nano. 2014;8:2148–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. White M, Webster G, O’Sullivan D, Stone S, La Flamme AC. Targeting innate receptors with MIS416 reshapes Th responses and suppresses CNS disease in a mouse model of multiple sclerosis. PLoS One. 2014;9:e87712.

    Article  PubMed Central  PubMed  Google Scholar 

  89. Maldonado R, LaMothe R, Ferrari J, Rossi R, Kolte P, Griset A, O’Neil C, et al. Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance. Proc Natl Acad Sci USA. 2015;112:156–65.

    Article  Google Scholar 

  90. Liu N, Dunphy DR, Atanassov P, Bunge SD, Chen Z, López GP, Boyle TJ, et al. Photoregulation of mass transport through a photoresponsive azobenzene-modified nanoporous membrane. Nano Lett. 2004;4:551–4.

    Article  CAS  Google Scholar 

  91. Khashab N, Trablosi A, Lau Y, Ambrogio M, Friedman D, Khatib H, Zink J, et al. Redox- and pH-controlled mechanized nanoparticles. Eur J Org Chem. 2009;2009(11):1669–73.

    Article  Google Scholar 

  92. Zhao Y, Trewyn BG, Slowing II, Lin VSY. Mesoporous silica nanoparticle-based double drug delivery system for glucose-responsive controlled release of insulin and cyclic AMP. J Am Chem Soc. 2009;131:8398–400.

    Article  CAS  PubMed  Google Scholar 

  93. Richardson TP, Peters MC, Ennett AB, Mooney DJ. Polymeric system for dual growth factor delivery. Nat Biotechnol. 2001;19:1029–34.

    Article  CAS  PubMed  Google Scholar 

  94. Almqvist KF, Dhollander A, Verdonk P, Forsyth R, Verdonk R, Verbruggen G. Treatment of cartilage defects in the knee using alginate beads containing human mature allogenic chondrocytes. Am J Sports Med. 2009;37:1920–9.

    Article  PubMed  Google Scholar 

  95. Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001;2002(19):3312–22.

    Google Scholar 

  96. Alberts DS, Muggia FM, Carmichael J, Winer EP, Jahanzeb M, Venook AP, Skubitz KM, Rivera E, Sparano JA, Dibella NJ, Stewart SJ, Kavanagh JJ, Gabizon AA. Efficacy and safety of liposomal anthracyclines in phase I/II clinical trials. Semin Oncol. 2004;2001(31):53–90.

    Article  Google Scholar 

  97. Koukourakis MI, Koukouraki S, Fezoulidis I, Kelekis N, Kyrias G, Archimandritis S, Karkavitsas N. High intratumoural accumulation of stealth liposomal doxorubicin (Caelyx®) in glioblastomas and in metastatic brain tumours. Br J Cancer. 2000;83:1281–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  98. Harris L, Batist G, Belt R, Rovira D, Navari R, Azarnia N, Welles L, et al. Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma. Cancer. 2002;94:25–36.

    Article  CAS  PubMed  Google Scholar 

  99. Batist G, Barton J, Chaikin P, Swenson C, Welles L. Myocet (liposome-encapsulated doxorubicin citrate): a new approach in breast cancer therapy. Expert Opin Pharmacother. 2002;3:1739–51.

    Article  CAS  PubMed  Google Scholar 

  100. Inaba K, Swiggard W, Inaba M, Meltzer J, Mirza A, Sasagawa T, Nussenzweig MC, et al. Tissue distribution of the DEC-205 protein that is detected by the monoclonal antibody NLDC-145. I. Expression on dendritic cells and other subsets of mouse leukocytes. Cell Immunol. 1995;163:148–56.

    Article  CAS  PubMed  Google Scholar 

  101. Guo M, Gong S, Maric S, Misulovin Z, Pack M, Mahnke K, Nussenzweig MC, et al. A monoclonal antibody to the DEC-205 endocytosis receptor on human dendritic cells. Hum Immunol. 2000;61:729–38.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are very grateful to Leah Messina of Approach Positive Marketing for designing Figs. 1, 2, and 3 within this review. I.T. was funded by the Bristol Myers Squibb Postdoctoral Fellowship and by NIH F32 HD081835. M.M was supported by a fellowship from the Cheryl Manne Fund for the Cure of MS. J.N.H.S was funded by a grant from the HT Langbert Charitable Trust Research Fund. P.W., K.B.S., M.M., and J.N.H.S. are associates of the Northeast NMO Consortium. We also thank Marlena Kern and Gila Klein for their assistance.

Author information

Author notes

    Authors and Affiliations

    1. Department of Neurobiology and Behavior, The Rockefeller University, New York, NY, USA

      Inna Tabansky & Joel N. H. Stern

    2. Department of Neurology, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, USA

      Mark D. Messina, Jeffrey Goldstein, Karen M. Blitz-Shabbir, Suly Machado, Paul Wright, Souhel Najjar & Joel N. H. Stern

    3. Department of Science Education, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, USA

      Mark D. Messina, Catherine Bangeranye, Jeffrey Goldstein, Suly Machado & Joel N. H. Stern

    4. Department of Autoimmunity, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY, USA

      Venkatesh Jeganathan, Yonghao Cao & Joel N. H. Stern

    5. School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA

      Warren Sands

    6. Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

      Warren Sands

    7. Department of Cancer Immunology and AIDS, Dana Farber-Harvard Cancer Institute, Boston, MA, USA

      Derin B. Keskin

    Authors
    1. Inna Tabansky
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Mark D. Messina
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Catherine Bangeranye
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Jeffrey Goldstein
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Karen M. Blitz-Shabbir
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Suly Machado
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Venkatesh Jeganathan
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Paul Wright
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Souhel Najjar
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Yonghao Cao
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Warren Sands
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Derin B. Keskin
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Joel N. H. Stern
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Joel N. H. Stern.

    Ethics declarations

    Conflict of interest

    The authors have no conflicts of interest to disclose.

    Additional information

    Inna Tabansky, Mark D. Messina and Joel N. H. Stern have contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Tabansky, I., Messina, M.D., Bangeranye, C. et al. Advancing drug delivery systems for the treatment of multiple sclerosis. Immunol Res 63, 58–69 (2015). https://doi.org/10.1007/s12026-015-8719-0

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12026-015-8719-0

    Keywords

    Search

    Navigation