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Mesoporous Silica Nanoparticle-Coated Microneedle Arrays for Intradermal Antigen Delivery
Authors:Jing Tu  Guangsheng Du  M. Reza Nejadnik  Juha Mönkäre  Koen van der Maaden  Paul H. H. Bomans  Nico A. J. M. Sommerdijk  Bram Slütter  Wim Jiskoot  Joke A. Bouwstra  Alexander Kros
Affiliation:1.Department of Supramolecular & Biomaterials Chemistry, Leiden Institute of Chemistry (LIC),Leiden University,Leiden,The Netherlands;2.Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR),Leiden University,Leiden,The Netherlands;3.Laboratory of Materials and Interface Chemistry & Center of Multiscale Electron Microscopy, Department of Chemical Engineering and Chemistry, and Institute for Complex Molecular Systems,Eindhoven University of Technology,Eindhoven,The Netherlands;4.Division of Biopharmaceutics, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR),Leiden University,Leiden,The Netherlands
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:
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