Mesoporous Silica Nanoparticle-Coated Microneedle Arrays for Intradermal Antigen Delivery

Pharm Res. 2017 Aug;34(8):1693-1706. doi: 10.1007/s11095-017-2177-4. Epub 2017 May 23.

Abstract

Purpose: To develop a new intradermal antigen delivery system by coating microneedle arrays with lipid bilayer-coated, antigen-loaded mesoporous silica nanoparticles (LB-MSN-OVA).

Methods: Synthesis of MSNs with 10-nm pores was performed and the nanoparticles were loaded with the model antigen ovalbumin (OVA), and coated with a lipid bilayer (LB-MSN-OVA). The uptake of LB-MSN-OVA by bone marrow-derived dendritic cells (BDMCs) was studied by flow cytometry. The designed LB-MSN-OVA were coated onto pH-sensitive pyridine-modified microneedle arrays and the delivery of LB-MSN-OVA into ex vivo human skin was studied.

Results: The synthesized MSNs demonstrated efficient loading of OVA with a maximum loading capacity of about 34% and the lipid bilayer enhanced the colloidal stability of the MSNs. Uptake of OVA loaded in LB-MSN-OVA by BMDCs was higher than that of free OVA, suggesting effective targeting of LB-MSN-OVA to antigen-presenting cells. Microneedles were readily coated with LB-MSN-OVA at pH 5.8, yielding 1.5 μg of encapsulated OVA per microneedle array. Finally, as a result of the pyridine modification, LB-MSN-OVA were effectively released from the microneedles upon piercing the skin.

Conclusion: Microneedle arrays coated with LB-MSN-OVA were successfully developed and shown to be suitable for intradermal delivery of the encapsulated protein antigen.

Keywords: intradermal antigen delivery; lipid bilayer; mesoporous silica nanoparticles; pH-sensitive microneedle arrays.

MeSH terms

  • Antigen-Presenting Cells / metabolism
  • Antigens / administration & dosage*
  • Drug Carriers
  • Drug Liberation
  • Humans
  • Hydrogen-Ion Concentration
  • Injections, Intradermal
  • Lipid Bilayers
  • Macrophages / metabolism
  • Nanoparticles / chemistry*
  • Needles*
  • Ovalbumin / administration & dosage*
  • Particle Size
  • Porosity
  • Silicon Dioxide / chemistry*
  • Skin
  • Surface Properties

Substances

  • Antigens
  • Drug Carriers
  • Lipid Bilayers
  • Silicon Dioxide
  • Ovalbumin