title: Laser-engineered dissolving microneedle arrays for protein delivery: potential for enhanced intradermal vaccination.
abstract: OBJECTIVE
  We aimed to highlight the utility of novel dissolving microneedle (MN)-based delivery systems for enhanced transdermal protein delivery. Vaccination remains the most accepted and effective approach in offering protection from infectious diseases. In recent years, much interest has focused on the possibility of using minimally invasive MN technologies to replace conventional hypodermic vaccine injections.
  
  
  METHODS
  The focus of this study was exploitation of dissolving MN array devices fabricated from 20% w/w poly(methyl vinyl ether/maleic acid) using a micromoulding technique, for the facilitated delivery of a model antigen, ovalbumin (OVA).
  
  
  RESULTS
  A series of in-vitro and in-vivo experiments were designed to demonstrate that MN arrays loaded with OVA penetrated the stratum corneum and delivered their payload systemically. The latter was evidenced by the activation of both humoral and cellular inflammatory responses in mice, indicated by the production of immunoglobulins (IgG, IgG1, IgG2a) and inflammatory cytokines, specifically interferon-gamma and interleukin-4. Importantly, the structural integrity of the OVA following incorporation into the MN arrays was maintained.
  
  
  CONCLUSIONS
  While enhanced manufacturing strategies are required to improve delivery efficiency and reduce waste, dissolving MN are a promising candidate for 'reduced-risk' vaccination and protein delivery strategies.
authors.affiliation: School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Belfast, UK.
authors.forename: Maelíosa T C
authors.initials: MT
authors.lastname: McCrudden
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Torrisi
authors.forename: Sharifah
authors.initials: S
authors.lastname: Al-Zahrani
authors.forename: Cian M
authors.initials: CM
authors.lastname: McCrudden
authors.forename: Marija
authors.initials: M
authors.lastname: Zaric
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Scott
authors.forename: Adrien
authors.initials: A
authors.lastname: Kissenpfennig
authors.forename: Helen O
authors.initials: HO
authors.lastname: McCarthy
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007834:Lasers; D008298:Maleates / Q000737:chemistry; D008738:Methyl Ethers / Q000737:chemistry; D051379:Mice; D008845:Microinjections; D009339:Needles; D010047:Ovalbumin / Q000008:administration & dosage; D011145:Polyvinyls / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility; D014611:Vaccination / Q000379:methods*; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000941:Antigens; C508598:IL4 protein, human; D008298:Maleates; D008738:Methyl Ethers; D011145:Polyvinyls; D014612:Vaccines; C510739:poly(vinyl methyl ether); D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; C030272:maleic acid
keywords: laser-engineering; microneedles; protein delivery; vaccination