Layer-by-layer assembly of DNA- and protein-containing films on microneedles for drug delivery to the skin.

Microneedle patches contain micrometer-scale needles coated with bioactive agents for minimally invasive drug delivery to the skin. In this study, we introduce layer-by-layer approaches to the fabrication of ultrathin DNA- and protein-containing polyelectrolyte films (or "polyelectrolyte multilayers", PEMs) on the surfaces of stainless steel microneedles. DNA-containing PEMs were fabricated on microneedles by the alternating deposition of plasmid DNA and a hydrolytically degradable poly(ß-amino ester). Protein-containing PEMs were fabricated using sodium poly(styrene sulfonate) (SPS) and bovine pancreatic ribonuclease A (RNase A) conjugated to a synthetic protein transduction domain. Layer-by-layer assembly resulted in ultrathin, uniform, and defect-free coatings on the surfaces of the microneedles, as characterized by fluorescence microscopy. These films eroded and thereby released DNA or protein when incubated in saline or when inserted into porcine cadaver skin and deposited DNA or protein along the edges of microneedle tracks to depths of ∼500 to 600 µm. We conclude that PEM-coated microneedles offer a novel and useful approach to the transdermal delivery of DNA- and protein-based therapeutics and could also prove useful in other applications.

Dissolving polymer microneedle patches for influenza vaccination.

Influenza prophylaxis would benefit from a vaccination method enabling simplified logistics and improved immunogenicity without the dangers posed by hypodermic needles. Here we introduce dissolving microneedle patches for influenza vaccination using a simple patch-based system that targets delivery to skin's antigen-presenting cells. Microneedles were fabricated using a biocompatible polymer encapsulating inactivated influenza virus vaccine for insertion and dissolution in the skin within minutes. Microneedle vaccination generated robust antibody and cellular immune responses in mice that provided complete protection against lethal challenge. Compared to conventional intramuscular injection, microneedle vaccination resulted in more efficient lung virus clearance and enhanced cellular recall responses after challenge. These results suggest that dissolving microneedle patches can provide a new technology for simpler and safer vaccination with improved immunogenicity that could facilitate increased vaccination coverage.