Nasal delivery of vaccines

The nasal delivery of vaccines is a very attractive route of administration in terms of efficacy and consumer friendliness. A population-wide immunization against influenza has yet to be achieved. The pain of injections discourages many people from receiving a flu shot. The nasal route offers the advantage of a mucosal response followed by a seric response, and has proved to be a very efficient mode of administration. ... 

A.J. Almeida, H.O. Alpar, Nasal delivery of vaccines. Journal of Drug Targeting 3 (1996) 455 67. 

Aerosol and nasal delivery of vaccines and antiviral drugs against seasonal and pandemic influenza. Expert Review of Respiratory Medicine, 4,... 

Almeida AJ, Alpar HO. 1996. Nasal delivery of vaccines. / Drug Target 3 455-467. 

SaatciF, Bozkir A. 2003. Nasal delivery of vaccines. Ankara University, J Faculty Pharm 32(3) 175-192. 

Since the uptake of particles in nasal epithelial tissue is known to be mostly mediated by M cells, nasal administration has been investigated as a noninva-sive delivery of vaccines [37], However, since the uptake of naked DNA by endocytocis is limited, use of either nanoparticles as mucosal delivery systems [37] or hypotonic shock [38] is reported for the efficient transfection of gene and vaccine into the nasal epithelium. It was also reported that polypeptides and polypeptide-coated nanospheres (diameter about 500 nm) are transported through endocytic process in rat M cells [39],... 

Coucke, D. Schotsaert, M. Libert, C. Pringels, E. Vervaet, C. Foreman, R Saelens, X. Remon, J.R Spray-dried powders of starch and crosslinked poly(acrylic acid) as carriers for nasal delivery of inactivated influenza vaccine. Vaccine 2009, 27 (8), 1279-1286. 

Iqbal, M., Lin, W., Jabbal-Gill, I., Davis, S.S., Steward, M.W., and lUum, L. 2003. Nasal delivery of chitosan-DNA plasmid expressing epitopes of respiratory syncytial virus (RSV) induces protective CTL responses in BALB/c mice. Vaccine. 21 1478-1485. 

Khatri, K., Goyal, A.K., Gupta, P.N., Mishra, N., Mehta, A., and Vyas, S.P. 2008b. Surface modified liposomes for nasal delivery of DNA vaccine. Vaccine. 26 2225-2233. 

The most potent mucosal adjuvants have been shown to be the toxins derived from Vibrio cholerae or Escherichia coli, which should not be surprising since these organisms invade the body through the GI tract. Obviously too toxic for human use because they are the source of cholera or diarrhoea, heat labile enterotoxins have been tested in mice and shown to be potent adjuvants for orally or nasally administered influenza vaccine. The potency of heat-labile enterotoxin mutants may also be enhanced by formulation into bioadhesive particulate delivery systems, and this is an area under current exploration. 

The nasal route is generating increasing interest as a route for the administration of local treatments and a cost-effective and patient-friendly alternative to injection for systemic delivery [49]. The special advantages of nasal delivery make it attractive for (i) crisis treatment where rapid onset of action is desirable (e.g., pain, migraine, panic attacks), (ii) systemic delivery of compounds that at present can only be delivered by injection (peptides/pro-proteins/vaccination), and (iii) direct targeting of the CNS (polar drugs for the treatment of CNS disorders). 

A number of adjuvants are awaiting approval for human use. The main impediment to the successful development of vaccine adjuvants is that their mechanism of action is not clearly understood. Table 5 offers a fist of available nasal drug delivery systems and the various adjuvants that have been used in the development of nasal vaccines. 

McNeela, E. A., O Connor, D., Gill, J. I., Ilium, L., Davis, S. S., Pizza, M., Peppoloni, S., Rappuoli, R., and Mills, G. H. K. ( 2000), A mucosal vaccine against diphtheria Formulation of cross reacting material (CRM197) of diphtheria toxin with chitosan enhances local and systemic antibodies and Th2 responses following nasal delivery, Vaccine., 19, 1188-1198. 

The use of dry powder formulations in nasal vaccine delivery has been extensively reviewed elsewhere [15-18], The association of vaccines to some of the par-... 

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