ReviewsPharmaceutical Aspects of Intranasal Delivery of Vaccines Using Particulate Systems
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INTRODUCTION
The continuous emergence of new pathogens and evolution of resistance of micro-organisms towards conventional drugs make it mandatory to continue to develop efficient vaccination strategies capable of producing acquired immune response, which is both antigen specific and possesses memory. The two important aspects of any successful vaccination strategy are to increase the potential to generate a potent defence against diseases that evade the immune system, and to develop long-lasting effective
OPPORTUNITIES AND CHALLENGES IN MUCOSAL VACCINE DELIVERY
Most significant viral and bacterial infections are acquired through the mucosal membranes of the respiratory, intestinal, lachrymal, or urogenital tract.10 Immunization via mucosal routes has been reported to induce both mucosal and systemic immune responses at least in some monogastric species including human,6 hence the potential usefulness of this strategy in the prevention of initial colonization of the mucosa by pathogenic microbes. The antibody-mediated protection at the mucosal surfaces
PHYSIOLOGY OF NASAL TISSUES
NALT, the prime inductive site for nasal mucosal immunity, is arranged on both sides of the nasopharyngeal duct in rodents.21, 22 The collection of oropharyngeal tissue and NALT equivalent tissues is called Waldeyer's ring in humans. The paired tubal tonsils, the paired palatine tonsils, a lingual tonsil, and nasopharyngeal tonsil or adenoids constitute the Waldeyer's ring.23, 24 They are the principal components of the mucosa-associated lymphoid tissue (MALT) of the human pharynx. Antigen
INTRANASAL VACCINE DELIVERY
The intranasal route of administration has an advantage over the oral route in that much lower doses of antigen are required because there is no significant dilution of the vaccine formulations by nasal fluids and no exposure to low pH or a broad range of secreted degradative enzymes.36 In addition, potent responses in the respiratory and genital tracts could be induced by intranasal immunization, as a consequence of the common mucosal immune system.37 The lower antigen dose requirement and
PARTICULATE SYSTEMS FOR INTRANASAL VACCINE DELIVERY
The nasal mucosa is an attractive option for vaccine delivery because of the absence of acidity, lack of abundant secreted enzymes and small mucosal surface area that result in a low dose requirement of antigen.39 The formulation of antigens in various particulate delivery systems for intranasal administration may be advantageous in the following ways: (i) protection of the antigen from mucosal enzymes; (ii) facilitating the preferential uptake of encapsulated antigen by specialized NALT M
PHARMACEUTICAL FACTORS AFFECTING NASAL PARTICULATE VACCINE DELIVERY
Performance of a nasal vaccine can be greatly influenced by the nature of the delivery system deployed and hence their importance is evident in the development of nasal vaccines. The major formulation factors related to nasal delivery of particulate vaccines are reviewed below.
DELIVERY DEVICES FOR INTRANASAL VACCINE ADMINISTRATION
Efficient delivery devices for intranasal administration of vaccines are crucial for the successful development and application of nasal vaccines. Intranasal delivery of vaccines pose two serious challenges: first is accurate and repeated dispensing of very small quantities of formulated vaccine and second is deposition of the formulated vaccine to all areas of the nasal mucosa (especially lymphoid tissues) while limiting the deposition of particles in the lung. Other aspects related to nasal
INDUSTRIAL AND REGULATORY ASPECTS
A small number of nasal vaccine delivery systems are under evaluation at various phases of clinical trials including a cochleate containing intranasal formulation for hepatitis B, a liposomal based intranasal influenza vaccine and a proteosome based formulation incorporating heat-labile E. coli enterotoxin (LTK63) as adjuvant for influenza.210 However, some vaccine products based on particulate delivery systems are licensed globally for the parenteral route of administration, for example,
CONCLUSIONS
The intranasal route of immunization has demonstrated several important advantages over the other routes, including noninvasiveness and the potential for the induction of enhanced immunity in the genitourinary, respiratory and gastrointestinal tracts. The pharmaceutical aspects of nasal immunization are critical for the successful development of nasal vaccines. Particulate delivery systems in combination with novel nasal spray devices can place intranasal immunization as the preferred route of
REFERENCES (249)
- et al.
The rational design of vaccines
Drug Discov Today
(2005) - et al.
Progress towards an AIDS mucosal vaccine: An overview
Tuberculosis
(2007) - et al.
Towards the rational design of Th1 adjuvants
Vaccine
(2001) - et al.
Enhanced mucosal and systemic immune response with intranasal immunization of mice with HIV peptides entrapped in PLG microparticles in combination with Ulex Europaeus-I lectin as M cell target
Vaccine
(2005) - et al.
Targeting dendritic cells with biomaterials: Developing the next generation of vaccines
Trends Immunol
(2006) - et al.
Current options for vaccine delivery systems by mucosal routes
J Control Release
(1997) - et al.
Selective transport of IgA. Cellular and molecular aspects
Gastroenterol Clin North Am
(1991) - et al.
Let's go mucosal: Communication on slippery ground
Trends Immunol
(2004) Induction of secretory immunity and memory at mucosal surfaces
Vaccine
(2007)- et al.
Regional specialization in the mucosal immune system: Primed cells do not always home along the same track
Immunol Today
(1999)