Insertion-responsive Microneedles for Rapid Intradermal Delivery of Canine Influenza Vaccine

J Control Release. 2018 Sep 28;286:460-466. doi: 10.1016/j.jconrel.2018.08.017. Epub 2018 Aug 11.


In this study, we present transcutaneous influenza vaccination using a novel tip-separable microneedle system called insertion-responsive microneedles (IRMNs). IRMNs are composed of dissolvable hyaluronic acid (HA) tips and biocompatible polycaprolactone (PCL) bases, the tip of which is instantly separated from the base during microneedle insertion and retraction. Vaccine antigens derived from canine influenza virus (A/canine/VC378/2012; H3N2) were successfully coated on HA tips by rapidly freezing the tips prior to coating. An ex vivo porcine skin insertion test showed that IRMNs were capable of penetrating the skin without tip breakage and releasing the coated materials within the skin. The thermal stability of the vaccine as determined by hemagglutination assay revealed that the coated vaccine partially maintained its activity when stored at 50 °C for 3 weeks, whereas the liquid form completely lost the activity. Immunization in guinea pigs showed that hemagglutination inhibition (HI) antibodies induced by IRMNs were two times higher than those induced by intramuscular (IM) injections. When challenged with influenza A/canine/Korea/01/2007 (H3N2) wild-type virus 2 weeks after the second vaccination, viral shedding was completely eliminated at 8 days post infection in both IRMNs and IM injection groups. Our results suggest that IRMNs have great potential for rapid and convenient vaccination, which will be particularly attractive for animal vaccinations.

Keywords: Canine influenza vaccine; Insertion-responsive microneedles; Patchless transdermal delivery; Rapid vaccine delivery; Tip-separable dissolving microneedles; Vaccine coating.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Dog Diseases / immunology
  • Dog Diseases / prevention & control*
  • Dogs
  • Drug Delivery Systems / economics
  • Drug Delivery Systems / instrumentation
  • Equipment Design
  • Female
  • Guinea Pigs
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology
  • Influenza Vaccines / therapeutic use
  • Injections, Intradermal
  • Microinjections / economics
  • Microinjections / instrumentation
  • Needles
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Swine
  • Time Factors
  • Vaccination / economics
  • Vaccination / instrumentation*


  • Influenza Vaccines