Formulation of Microneedles Coated with Influenza Virus-like Particle Vaccine

Article (PDF Available)inAAPS PharmSciTech 11(3):1193-201 · September 2010with33 Reads
DOI: 10.1208/s12249-010-9471-3 · Source: PubMed
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
    • "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). "
    [Show abstract] [Hide abstract] 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.
    Article · May 2015
    • "Each MN array consisted of single rows of five microneedles (50 in total) with 700 mm length, 200 mm width from the base and 50 mm 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 shownTable 2 the coating solutions composed of three anticancer agents, 5FU, CRC and CPT, with different water solubilities and the graft water soluble polymer Soluplus. "
    [Show abstract] [Hide abstract] ABSTRACT: A novel inkjet printing technology is introduced as a process to coat metal microneedle arrays with three anticancer agents 5-fluororacil, curcumin and cisplatin for transdermal delivery. The hydrophilic graft copolymer Soluplus® was used as a drug carrier and the coating formulations consisted of drug-polymer solutions at various ratios. A piezoelectric dispenser jetted microdroplets on the microneedle surface to develop uniform, accurate and reproducible coating layers without any material losses. Inkjet printing was found to depend on the nozzle size, the applied voltage (mV) and the duration of the pulse (μs). The drug release rates were determined in vitro using Franz type diffusion cells with dermatomed porcine skin. The drug release rates depended on the drug-polymer ratio, the drug lipophilicity and the skin thickness. All drugs presented increased release profiles (750 μm skin thickness), which were retarded for 900 μm skin thickness. Soluplus assisted the drug release especially for the water insoluble curcumin and cisplatin due to its solubilizing capacity. Inkjet printing was proved an effective technology for coating of metal microneedles which can then be used for further transdermal drug delivery applications. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jan 2015
    • "A study involving the administration of Gardasil, a commercially approved prophylactic human cervical cancer vaccine composed of the L1 VLP capsid of human papillomavirus , was reported to induce higher virus neutralizing antibody titers in C57BL/6 mice when delivered via Nanopatch, a densely-packed microprojection array, than by intramuscular immunization [26]. 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 trehaloseinclusive formulations [28] . "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Jan 2014
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