Poly[di(carboxylatophenoxy)phosphazene] is a potent adjuvant for intradermal immunization

Andrianov, Alexander K.; DeCollibus, Daniel P.; Gillis, Helice A.; Kha, Henry H.; Marin, Alexander; Prausnitz, Mark R.; Babiuk, Lorne A.; Townsend, H. G. G.; Mutwiri, George

doi:10.1073/pnas.0908842106

Cited by 141 publications

(116 citation statements)

References 45 publications

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“…Microneedles have been fabricated by adapting manufacturing tools from the microelectronics industry to produce micron-scale needles that painlessly pierce the outer barrier layer of the skin to administer vaccine in a simple manner using a patch-like format. Microneedle patches are small and simple enough to use that they could be distributed through pharmacies or the mail and might be self-administered by patients (10) Solid microneedle patches have been coated with vaccines, including the model antigen ovalbumin (11), hepatitis B surface antigen (12), and inactivated influenza virus (13)(14)(15). In addition, hollow microneedles have previously been used to inject influenza vaccine into the skin of human subjects (16) and solid microneedles have been used to scrape the skin for delivery of DNA and other vaccines (17), although these methods do not lend themselves as easily to rapid distribution or self-administration.…”

Section: Introductionmentioning

confidence: 99%

Formulation of Microneedles Coated with Influenza Virus-like Particle Vaccine

et al. 2010

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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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Section: Introductionmentioning

confidence: 99%

Formulation of Microneedles Coated with Influenza Virus-like Particle Vaccine

et al. 2010

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“…It is a water-soluble molecule, which can be easily formulated with proteins and has the capacity to dissolve in a highly hydrated environment. Owing to this dual functionality of PCPP (as an adjuvant and film-forming nature), it is one of the most promising materials available for use in vaccine delivery [82].…”

Section: Polyphosphazenesmentioning

confidence: 99%

Applications of polymeric adjuvants in studying autoimmune responses and vaccination against infectious diseases

Shakya

Nandakumar

2013

J. R. Soc. Interface.

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Polymers as an adjuvant are capable of enhancing the vaccine potential against various infectious diseases and also are being used to study the actual autoimmune responses using self-antigen(s) without involving any major immune deviation. Several natural polysaccharides and their derivatives originating from microbes and plants have been tested for their adjuvant potential. Similarly, numerous synthetic polymers including polyelectrolytes, polyesters, polyanhydrides, non-ionic block copolymers and external stimuli responsive polymers have demonstrated adjuvant capacity using different antigens. Adjuvant potential of these polymers mainly depends on their solubility, molecular weight, degree of branching and the conformation of polymeric backbone. These polymers have the ability not only to activate humoral but also cellular immune responses in the host. The depot effect, which involves slow release of antigen over a long duration of time, using different forms (particulate, solution and gel) of polymers, and enhances the co-stimulatory signals for optimal immune activation, is the underlying principle of their adjuvant properties. Possibly, polymers may also interact and activate various toll-like receptors and inflammasomes, thus involving several innate immune system players in the ensuing immune response. Biocompatibility, biodegradability, easy production and purification, and non-toxic properties of most of the polymers make them attractive candidates for substituting conventional adjuvants that have undesirable effects in the host.

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“…[2,7] Microneedles have been designed to be coated with the drug or to encapsulate the drug for release into the skin by dissolution. [8][9][10][11] Hollow microneedles have been coupled with a syringe for active drug infusion. [12][13][14] L-Ascorbic acid (vitamin C), a representative water-soluble vitamin, has a variety of biological, pharmaceutical and dermatological functions; it promotes collagen biosynthesis, provides photoprotection, causes melanin reduction, scavenges free radicals, and enhances the immunity (antiviral effect).…”

Section: Introductionmentioning

confidence: 99%

Enhancement of skin permeation of vitamin C using vibrating microneedles

Lee

Baek

Kwag

et al. 2017

Transl Clin Pharmacol

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This study was performed to evaluate the use of vibrating microneedles for the transdermal delivery of vitamin C. The microneedles were designed to vibrate at three levels of intensity. In vitro permeation by vitamin C was evaluated according to the specific conditions such as vibration intensity (levels 1, 2 and 3), application time (1, 3, 5, 7 and 10 min), and application power (500, 700 and 1,000 g). The highest permeation of vitamin C was observed at level 3 of vibration intensity, 5 min of application, and 1,000 g of application power. Vitamin C gel showed no cytotoxic effect against Pam212 cells or skin irritation effects. A pharmacokinetic study of the gel in rats was conducted under optimized conditions. The AUC 0 -∞ and C max increased 1.35-fold and 1.44-fold, respectively, compared with those after vitamin C gel without application with vibrating microneedles. The present study suggests that vibrating microneedles can be used to facilitate the skin permeability of vitamin C under optimal conditions.

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Poly[di(carboxylatophenoxy)phosphazene] is a potent adjuvant for intradermal immunization

Cited by 141 publications

References 45 publications

Formulation of Microneedles Coated with Influenza Virus-like Particle Vaccine

Formulation of Microneedles Coated with Influenza Virus-like Particle Vaccine

Applications of polymeric adjuvants in studying autoimmune responses and vaccination against infectious diseases

Enhancement of skin permeation of vitamin C using vibrating microneedles

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