Formulation of Microneedles Coated with Influenza Virus-like Particle Vaccine

Abstract

Abstract. Mortality due to seasonal and pandemic influenza could be reduced by increasing the speed of influenza vaccine production and distribution. We propose that vaccination can be expedited by (1) immunizing with influenza virus-like particle (VLP) vaccines, which are simpler and faster to manufacture than conventional egg-based inactivated virus vaccines, and (2) administering vaccines using microneedle patches, which should simplify vaccine distribution due to their small package size and possible self-administration. In this study, we coated microneedle patches with influenza VLP vaccine, which was released into skin by dissolution within minutes. Optimizing the coating formulation required balancing factors affecting the coating dose and vaccine antigen stability. Vaccine stability, as measured by an in vitro hemagglutination assay, was increased by formulation with increased concentration of trehalose or other stabilizing carbohydrate compounds and decreased concentration of carboxymethylcellulose (CMC) or other viscosity-enhancing compounds. Coating dose was increased by formulation with increased VLP concentration, increased CMC concentration, and decreased trehalose concentration, as well as increased number of dip coating cycles. Finally, vaccination of mice using microneedles stabilized by trehalose generated strong antibody responses and provided full protection against high-dose lethal challenge infection. In summary, this study provides detailed analysis to guide formulation of microneedle patches coated with influenza VLP vaccine and demonstrates effective vaccination in vivo using this system.

Inkjet printing of transdermal microneedles for the delivery of anticancer agents

“…Each MN array consisted of single rows of five microneedles (50 in total) with 700 m length, 200m width from the base and 50m thickness. Previous studies (Kim et al, 2010) have shown that coating of MNs requires proper design of coating formulations in order to achieve uniform coatings and avoid the creation of bulky layers. As shown in Table 2 the coating solutions composed of three anticancer agents, 5FU, CRC and CPT, with different water solubilities and the graft water soluble polymer Soluplus.…”

Long-Term Protective Immunity from an Influenza Virus-Like Particle Vaccine Administered with a Microneedle Patch

“…Microneedle preparations and coatings were performed as described previously (27,30). Briefly, rows of solid metal microneedles were fabricated by cutting needle structures from stainless sheets (SS304, 75-m thickness; McMaster-Carr, Atlanta, GA) using an infrared laser (Resonetics Maestro, Nashua, NH), and the microneedles measured 700 m in length and 160 m in width.…”

Potential of microneedle-assisted micro-particle delivery by gene guns: a review

“…The most common materials used for fabricating MN are metal, silicon and polymer (Zhao et al, 2006;Memon et al, 2011;Kim et al, 2012). The primary metals used for MNs are stainless steel (Martanto et al, 2004;Bal et al, 2008;Quan et al, 2010;Kim et al, 2012) and titanium (Parker et al, 2007;Fernandez et al, 2009;Kim et al, 2010). Metal MNs have the advantages of low cost, tougher hardness, ease of penetration into the tissue and they are not easily broken in the tissue.…”