Innovative delivery technologies for the needle-free delivery of vaccines by the intranasal route offer advantages to traditional
parenteral needle-based delivery systems developed and produced by the vaccine industry. Dry powder intranasal vaccine technologies
have recently been developed. In addition, a rapid manufacturing technology platform is described that offers distinct advantages
for delivery of liquid vaccines, with future development for a breakthrough in situ aseptic reconstitution technology for freeze-dried or spray-dried vaccine powders. This latter advance offers the potential
for eliminating or markedly reducing the need for cold-chain management of vaccines during transport and storage. These new
technologies have wide-ranging applications and advantages for the reliable and effective administration of vaccine products.
Successful large-scale immunization of populations around the globe with vaccines calls for a convenient mode of drug delivery
with accurate dosing, preferably with limited need for specialized training of health workers. As interest grows in immunizing
large segments of the global population with vaccines for widespread diseases such as pandemic influenza, malaria, tuberculosis,
and rotavirus infections, comes the pressing need for innovative technologies that can facilitate a more responsive and cost-effective
process, and also can circumvent the drawbacks of conventional modes of syringe-based vaccine delivery.
(MYSTIC PHARMACEUTICALS, INC.)
Vaccines for potential bio-threat agents such as anthrax, plague, or Ebola virus infections also necessitate technologies
compatible with ease of delivery, stockpiling ability, a rapid manufacturing paradigm, rapid deployment, and under certain
high risk conditions, the capability to self-administer. In particular, needle-free methods of vaccine administration are
appealing alternatives to injected vaccines in these scenarios.
Needle-based vaccine injections require highly trained health workers and an optimally performing system for effective mass
vaccination campaigns. The universal fear of needle sticks is an indicator of the need of convenient and viable alternative
modes of delivery. Cold-chain management of vaccines is also often necessary, and lyophilized vaccines necessitate reconstitution
in diluents at the time of use under sterile conditions, often in adverse field situations. Oral vaccines or transcutaneous
vaccine patches have been used but also have drawbacks such as inconsistent absorption, gastrointestinal degradation, or high
Intranasal delivery of drugs and biologics is a rapidly growing means of medicinal prophylaxis and therapy, and offers compelling
advantages as a needle-free approach for testing and demonstrating the efficacy of existing and new drugs and vaccines.1 The nasal mucosa provides a convenient surface for vaccine deposition and for induction of systemic and local mucosal immunity.
Recent advances in the development of delivery platforms are in response to the demand for innovative approaches to intranasal
vaccine delivery that are safer, can be rapidly manufactured cost effectively, and assure compatibility with a wide range
of vaccines and biopharmaceuticals. A key benefit of an intranasal vaccine is its potential to induce both mucosal and humoral
A distinct advantage of intranasal drug delivery is that drug uptake into the blood circulatory system by absorption through
the nasal mucosa can be quite rapid.2,3 Moreover, clinical studies have demonstrated that a rapid local immune response can be achieved within 24–48 hours using
intranasal delivery, providing rapid protection against airborne pathogens that enter the body through the respiratory tract.
Clinical evidence has also demonstrated that complete systemic immunity can be achieved in significantly less time (days versus
weeks) through the intranasal route.
An optimal intranasal drug delivery platform must be designed to provide accurate and precise delivery through optimized device
design, such that the amount of drug or vaccine for each dose must be consistent. Advantages of intranasal vaccine delivery
versus administration by oral or injection routes include a more rapid circulatory uptake at a lower dose than by parenteral
or oral drug delivery, lower cost, avoidance of needles, avoidance of losses caused by intestinal passage for oral drugs and
first pass liver metabolism, and greater user compliance. These and other differences can translate to a capability for lower
effective doses, more rapid physiological response, and fewer complications caused by a vaccine's adverse effects.
Intranasal delivery of an inactivated influenza vaccine has been reported to have an elevated risk for Bell's palsy.4 However, Centers for Disease Control and Prevention studies of 10 years of clinical data concluded that elevated Bell's
palsy risk was also observed for parenteral injection delivery of inactivated flu vaccines, demonstrating that intranasal
delivery of vaccines was not associated with any Bell's palsy risk.5