Formulation of Microneedles Coated with Influenza Virus-like Particle Vaccine

School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Dr, Atlanta, Georgia 30332, USA.
AAPS PharmSciTech (Impact Factor: 1.64). 09/2010; 11(3):1193-201. DOI: 10.1208/s12249-010-9471-3
Source: PubMed

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.

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Available from: Yeu-Chun Kim, Sep 27, 2015
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    • "A vaccine patch with MNs was prepared by fabricating arrays of solid MNs and coating vaccine antigen on the surface of MNs as described previously [20] [21]. Briefly, rows of solid metal microneedles were made by wet-etching photolithographically defined needle structures from stainless steel sheets (Tech Etch, Plymouth, MA). "
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    ABSTRACT: A broadly cross-protective influenza vaccine that can be administrated by a painless self-immunization method would be a value as a potential universal mass vaccination strategy. This study developed a minimally-invasive microneedle (MN) patch for skin vaccination with virus-like particles containing influenza virus heterologous M2 extracellular (M2e) domains (M2e5x VLPs) as a universal vaccine candidate without adjuvants. The stability of M2e5x VLP-coated microneedles was maintained for 8weeks at room temperature without losing M2e antigenicity and immunogenicity. MN skin immunization induced strong humoral and mucosal M2e antibody responses and conferred cross-protection against heterosubtypic H1N1, H3N2, and H5N1 influenza virus challenges. In addition, M2e5x VLP MN skin vaccination induced T-helper type 1 responses such as IgG2a isotype antibodies and IFN-γ producing cells at higher levels than those by conventional intramuscular injection. These potential immunological and logistic advantages for skin delivery of M2e5x VLP MN vaccines could offer a promising approach to develop an easy-to-administer universal influenza vaccine. Copyright © 2015. Published by Elsevier B.V.
    Journal of Controlled Release 05/2015; 210. DOI:10.1016/j.jconrel.2015.05.278 · 7.71 Impact Factor
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    • "Furthermore, the optimization parameters of VLP have been investigated with a vaccine formulation composed of the M1 matrix protein and the HA subunit of H1N1 A/PR/8/34 influenza virus strain [27]. A stability test comparing the antigenicity of influenza VLP vaccines including or devoid of trehalose was conducted, which showed that vaccine solutions without the stabilizer were not as effective as trehalose-inclusive formulations [28]. "
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    ABSTRACT: In today's medical industry, the range of vaccines that exist for administration in humans represents an eclectic variety of forms and immunologic mechanisms. Namely, these are the live attenuated viruses, inactivated viruses, subunit proteins, and virus-like particles for treating virus-caused diseases, as well as the bacterial-based polysaccharide, protein, and conjugated vaccines. Currently, a new approach to vaccination is being investigated with the concept of DNA vaccines. As an alternative delivery route to enhance the vaccination efficacy, microneedles have been devised to target the rich network of immunologic antigen-presenting cells in the dermis and epidermis layers under the skin. Numerous studies have outlined the parameters of microneedle delivery of a wide range of vaccines, revealing comparable or higher immunogenicity to conventional intramuscular routes, overall level of stability, and dose-sparing advantages. Furthermore, recent mechanism studies have begun to successfully elucidate the biological mechanisms behind microneedle vaccination. This paper describes the current status of microneedle vaccine research.
    01/2014; 3(1):42-49. DOI:10.7774/cevr.2014.3.1.42
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    • "They could be preferred for slow release of active pharmaceutical ingredients (APIs), and heat resistive APIs [14], [35], [36]. Poly lactic-co-glycolic acid (PLGA) [37], polycarbonate [38], poly lactic acid (PLA) [30], poly glycolic acid (PGA) [37], and polystyrene [39] were produced as biodegradable MNs. "
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    ABSTRACT: Microfabrication of dissolvable, swellable, and biodegradable polymeric microneedle arrays (MNs) were extensively investigated based in a nano sensitive fabrication style known as micromilling that is then combined with conventional micromolding technique. The aim of this study was to describe the polymer selection, and optimize formulation compounding parameters for various polymeric MNs. Inverse replication of micromilled master MNs reproduced with polydimethylsiloxane (PDMS), where solid out of plane polymeric MNs were subsequently assembled, and physicochemically characterized. Dissolvable, swellable, and biodegradable MNs were constructed to depth of less than 1 mm with an aspect ratio of 3.6, and 1/2 mm of both inter needle tip and base spacing. Micromolding step also enabled to replicate the MNs very precisely and accurate. Polymeric microneedles (MN) precision was ranging from ±0.18 to ±1.82% for microneedle height, ±0.45 to ±1.42% for base diameter, and ±0.22 to ±0.95% for interbase spacing. Although dissolvable sodium alginate MN showed less physical robustness than biodegradable polylactic-co-glycolic acid MN, their thermogravimetric analysis is of promise for constructing these polymeric types of matrix devices.
    PLoS ONE 10/2013; 8(10):e77289. DOI:10.1371/journal.pone.0077289 · 3.23 Impact Factor
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