The extracellular domain of influenza A ion channel membrane matrix protein 2 (M2e) is considered to be a potential candidate to develop a universal influenza A vaccine. However poor immunogenicity of M2e presents a significant roadblock. We have developed a vaccine formulation comprising of the consensus M2e peptide conjugated to gold nanoparticles (AuNPs) with CpG as a soluble adjuvant (AuNP-M2e+sCpG). We demonstrate that intranasal delivery of AuNP-M2e+sCpG in mice induces lung B cell activation and robust serum anti-M2e immunoglobulin G (IgG) response, with stimulation of both IgG1 and IgG2a subtypes. Using Madin-Darby canine kidney (MDCK) cells infected with A/California/04/2009 (H1N1pdm) pandemic strain, or A/Victoria/3/75 (H3N2), or the highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1) as immunosorbants we further show that the antibodies generated are also capable of binding to the homotetrameric form of M2 expressed on infected cells. Lethal challenge of vaccinated mice with A/California/04/2009 (H1N1pdm) pandemic strain, A/Victoria/3/75 (H3N2), and the highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1) led to 100%, 92%, and 100% protection, respectively. Overall, this study helps to lay the foundation of a potential universal influenza A vaccine.
A coated microneedle array comprises sharp micrometer-sized needle shafts attached to a base substrate and coated with a drug on their surfaces. Coated microneedles are under investigation for drug delivery into the skin and other tissues, and a broad assortment of active materials, including small molecules, peptides, proteins, deoxyribonucleic acids, and viruses, have been coated onto microneedles. To coat the microneedles, different methods have been developed. Some coating methods achieve selective coating of just the microneedle shafts, whereas other methods coat not only microneedle shafts but also the array base substrate. Selective coating of just the microneedle shafts is more desirable since it provides control over drug dosage, prevents drug waste, and offers high delivery efficiency. Different excipients are added to the coating liquid to modulate its viscosity and surface tension in order to achieve uniform coatings on microneedles. Coated microneedles have been used in a broad range of biomedical applications. To highlight these different applications, a table summarizing the different active materials and the amounts coated on microneedles is provided. We also discuss factors that should be considered when deciding suitability of coated microneedles for new-drug delivery applications. In recent years, many coated microneedles have been investigated in human clinical trials, and there is now a strong effort to bring the first coated microneedle-based product to market.
Metallic microneedles are attractive for painless transdermal drug-delivery. However, fabrication techniques for metal microneedles are often complex and multi-step. In this study, a scalable manufacturing of metallic microneedle arrays is presented using thermoplastic drawing of metallic glasses. Microneedles with tunable lengths and tips are produced by controlling the rheology and fracture of metallic glass. The same drawing process can generate solid and hollow microneedles simply by varying the thickness of metallic glass. The mechanism of thickness dependent transition from solid to hollow profiles is described by the viscous buckling of metallic liquid. In vitro skin insertion tests demonstrate that both solid and hollow metallic glass microneedles can pierce porcine skin and deliver model drugs.
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