Inhibitory/suppressive oligodeoxynucleotide nanocapsules as simple oral delivery devices for preventing atopic dermatitis in mice

Mol Ther. 2015 Feb;23(2):297-309. doi: 10.1038/mt.2014.239. Epub 2014 Dec 15.

Abstract

Here, we report a simple and low-cost oral oligodeoxynucleotide (ODN) delivery system targeted to the gut Peyer's patches (PPs). This system requires only Dulbecco's modified eagle's medium, calcium chloride, ODNs, and basic laboratory equipment. ODN nanocapsules (ODNcaps) were directly delivered to the PPs through oral administration and were taken up by macrophages in the PPs, where they induced an immune response. Long-term continuous oral dosing with inhibitory/suppressive ODNcaps (iODNcaps, "iSG3caps" in this study) was evaluated using an atopic dermatitis mouse model to visually monitor disease course. Administration of iSG3caps improved skin lesions and decreased epidermal thickness. Underlying this effect is the ability of iSG3 to bind to and prevent phosphorylation of signal transducer and activator of transcription 6, thereby blocking the interleukin-4 signaling cascade mediated by binding of allergens to type 2 helper T cells. The results of our iSG3cap oral delivery experiments suggest that iSG3 may be useful for treating allergic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Dermatitis, Atopic / immunology*
  • Dermatitis, Atopic / pathology
  • Dermatitis, Atopic / prevention & control
  • Dermatitis, Atopic / therapy
  • Disease Models, Animal
  • Drug Delivery Systems*
  • Interleukin-33 / biosynthesis
  • Macrophage Activation / genetics
  • Macrophage Activation / immunology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Mice
  • Nanocapsules* / ultrastructure
  • Oligodeoxyribonucleotides / administration & dosage*
  • Oligodeoxyribonucleotides / immunology*
  • Peyer's Patches / immunology
  • Peyer's Patches / metabolism
  • Signal Transduction / drug effects
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • Interleukin-33
  • Nanocapsules
  • Oligodeoxyribonucleotides