Dry Powder Intranasal Vaccine Delivery
Advances in dry powder formulation and nanotechnology-based processes have made it possible for new intranasal delivery systems
for vaccines to be developed. Dry powder formulations can afford better stability characteristics for a vaccine and potentially
reduce the requirements for cold-chain management or the addition of preservatives. In some instances, a dry powder intranasal
form of a vaccine may prove to be superior to its injected counterpart. A dry powder anthrax vaccine has been developed that
afforded better protection against anthrax spore challenge than an intramuscular injection.6
The GelVac technology developed by DelSite Biotechnologies (Irving, TX) consists of dry powder formulations of a vaccine with
a natural plant-derived acidic polysaccharide material which is administered into the nasal cavity. On contact with the nasal
mucosa, the formulation generates a muco-adhesive gel, entrapping the vaccine antigen, and providing a mechanism for the prolonged
exposure of the antigen to the nasal mucosal tissue to enhance the immune response. This method of vaccine delivery is potentially
adaptable to inactivated antigens, live attenuated viruses, and DNA vaccines.
The Becton Dickinson (BD, Franklin Lakes, NJ) T107 Dry Powder Inhaler, developed primarily for inhalation, may also be adapted
to intranasal vaccine delivery. In this innovation, air from a syringe barrel ruptures the membrane of a capsule containing
the vaccine, which can be propelled into the nasal passages. This method of delivery is being adopted for influenza and anthrax
vaccines. The related BD Accuspray syringe-based system is being evaluated for use with the NASVAC HBsAg +HBcAg hepatitis
Optinose, Ltd. (Wiltshire, UK), developed an exhalation-actuated device that delivers intranasal drugs to the nasal cavity
without lung deposition of the aerosol known as the Optimist for bidirectional intranasal drug and vaccine delivery. A process
for the production of stable, respirable powder vaccines has been developed by Aktiv-Dry LLC, (Boulder, CO) based on innovations
from the laboratory of Bob Sievers at the University of Colorado. This technology is based on carbon dioxide assisted nebulization
with a bubble dryer that rapidly and efficiently converts a liquid vaccine product into a dry powder formulation. This has
been used in the production of a novel stabilized measles virus inhalation vaccine; the methodology could be readily adaptable
for intranasal vaccine delivery as well.
VersiDoser Intranasal Delivery Platform
An intranasal delivery system has been developed by Mystic Pharmaceuticals for human applications (Figure 1) that is novel,
simple, disposable, and capable of precise aseptic delivery of formulations in the form of an optimized plume for maximum
deposition to, and rapid systemic uptake by, the nasal mucosa.
Figure 1. VersiDoser intranasal delivery devices developed by Mystic Pharmaceuticals. Left: actuation of the device; Right:
multilayer laminate unit dose blister containing both the vaccine formulation and Vjet nozzle.
The technology platform for intranasal delivery developed by Mystic Pharmaceuticals is called the VersiDoser (Figure 1).7 The capability to self-administer reduces the need for extensive field training by healthcare operators, and eliminates
the "sharps" needle disposal problem and biohazards associated with used contaminated syringes. The VersiDoser delivery platform
includes an aseptic unit-dose packaging production capability for fill, fit, and finish production of up to 300,000 doses
per day, per line. Such a rapid production capability can significantly reduce the need to establish and maintain large cold-chain
managed stockpiles of prefilled syringes while enabling a rapid response capability to produce vaccine when combined with
rapid vaccine or drug production capabilities.
To ensure the sterility of a vaccine formulation (without a requirement for an added preservative), Mystic has developed a
unit-dose blister that contains a single dose of the vaccine formulation (Figure 2).
Figure 2. Mystic Pharmaceuticals' Versidoser unit-dose blister with Vjet nozzle
The VersiDoser delivery platform uses a proprietary aseptic form-fill-seal (FFS) unit-dose manufacturing process and technology
to produce and fill blisters with a liquid vaccine or drug formulation. The blisters are USP Class VI or ISO10993 compliant
multilayer laminates comprising foil and plastic resin layers. The laminate is matched with a specific vaccine formulation
to assure chemical compatibility and product stability. In each blister is a VJet nozzle to ensure the intranasal delivery
of optimum aerosol plume geometry for the formulation.
The Vjet is a precision-matched specially engineered piercer nozzle that is optimized to the physical properties and dose
volumes of the vaccine or drug formulation being delivered and is injection molded from USP Class VI resins. Computational
fluid dynamics modeling is combined with analytical testing to provide a customized solution for each product formulation.
The VersiDoser unit-dose blisters can deliver dose volumes ranging from 15 to 500 μL.
The FFS drug filling, packaging, and sealing operations are conducted in an automated production system enclosed in a barrier
isolator to ensure aseptic technique and minimize defect opportunities. The production system can be configured for the manufacture
and packaging of live or killed virus vaccines, bacterial vaccines, or recombinant protein or DNA vaccines. After they are
filled with the vaccine formulation, the blisters are packaged into drug delivery devices such as those shown in Figure 1.
The illustrated disposable delivery system is compact, and cost effective for use in global-scale quantities. For bioterrorism
or pandemic preparedness, numerous units could be stockpiled for distribution to the target location where they can be distributed
for self-administration. After use, the delivery device locks to avoid reuse and can be discarded.
The VersiDoser intranasal delivery platform includes disposable delivery systems for mono-dose, bi-dose, dual-dose, and reloadable
vaccine delivery. The dual-dose system can deliver a vaccine or drug formulation into both nostrils simultaneously, which
would be applicable for a therapeutic requiring high dose volume in health emergencies or rescue situations. Alternative delivery
systems under development include a reloadable vaccine dispenser for mass vaccination campaigns requiring administration of
thousands of individual doses (Figure 3).
Figure 3. Multiple dose intranasal delivery system with reloadable vaccine blister tips