Design and characterisation of a dissolving microneedle patch for intradermal vaccination with heat-inactivated bacteria: A proof of concept study

Int J Pharm. 2018 Oct 5;549(1-2):87-95. doi: 10.1016/j.ijpharm.2018.07.049. Epub 2018 Jul 23.

Abstract

This work describes the formulation and evaluation of dissolving microneedle patches (MNs) for intradermal delivery of heat-inactivated bacteria. Pseudomonas aeruginosa, strain PA01, was used as a model bacterium. Utilising a simple, cost effective fabrication process, P. aeruginosa was heat-inactivated and formulated into dissolving MNs, fabricated from aqueous blends of 20% w/w poly(methylvinylether/maleic acid). The resultant MNs were of sufficient mechanical strength to consistently penetrate a validated skin model Parafilm M®, inserting to a depth of between 254 and 381 µm. MNs were successfully inserted into murine skin and partially dissolved. Analysis of MN dissolution kinetics in murine ears via optical coherence tomography showed almost complete MN dissolution 5 min post-insertion. Mice were vaccinated using these optimised MNs by application of one MN to the dorsal surface of each ear (5 min). Mice were subsequently challenged intranasally (24 h) with a live culture of P. aeruginosa (2 × 106 colony forming units). Bacterial load in the lungs of mice vaccinated with P. aeruginosa MNs was significantly (p = 0.0059) lower than those of their unvaccinated counterparts. This proof of concept work demonstrates the potential of dissolving MNs for intradermal vaccination with heat-inactivated bacteria. MNs may be a cost effective, potentially viable delivery system, which could easily be implemented in developing countries, allowing a rapid and simplified approach to vaccinating against a specific pathogen.

Keywords: Heat-inactivated bacteria; Intradermal; Microneedle; Skin; Vaccine.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Bacterial Vaccines / administration & dosage*
  • Drug Delivery Systems*
  • Hot Temperature
  • Injections, Intradermal
  • Maleates / chemistry
  • Mice
  • Microinjections
  • Needles
  • Polyethylenes / chemistry
  • Proof of Concept Study
  • Pseudomonas aeruginosa / immunology*
  • Skin / metabolism
  • Solubility
  • Tomography, Optical Coherence
  • Vaccination / methods*

Substances

  • Bacterial Vaccines
  • Maleates
  • Polyethylenes
  • poly(methyl vinyl ether-co-maleic anhydride)