Vaccines delivery

Chitosan has proven to be an excellent vehicle for vaccine delivery through intranasal route. The mucoadhesiveness of chitosan helps in retaining the vaccine inside the nasal passage and the tight endothelial cell junctions get opened up for paracellular transport of vaccine [147,148]. 

Chitosan has been fabricated for delivery of tumor vaccines in the form of micro-and nanoparticulate delivery systems, which favor the uptake of antigens by the mucosal lymphoid tissues, stimulating a strong immune response against the antigens. 

Chitosan microparticles have also been fabricated for oral vaccination, even though it is difficult to avoid the degradation of vaccine in the gut region. The in-vivo uptake of vaccine by murine Peyer s patches was remarkably good, proving it to be an efficient tool in vaccine delivery system [150]. 

---

Since these vaecines are imable to evoke a natural infection profile with respeet to the release of antigen they must be administered on a number of occasions. Immunity is not complete until the course of immunization is complete and, with the exeeption of toxin-dominated diseases (diphtheria, tetanus) where the immimogen is a toxoid, will never match the performance of live vaccine delivery. Specificity of the immrme resporrse generated in the patient is initially low. This is particularly the case when the vaeeine is composed of a relatively crude cocktail of killed cells where the immime response is direeted only partly towards antigenic components of the cells that are assoeiated with the infeetion process. This increases the possibility of adverse reaetions in the patient. 

Despite the evidence for the cytotoxicity of CNTs, there are an increasing number of published studies that support the potential development of CNT-based biomaterials for tissue regeneration (e.g., neuronal substrates [143] and orthopedic materials [154—156]), cancer treatment [157], and drug/vaccine delivery systems [158, 159]. Most of these applications will involve the implantation and/or administration of such materials into patients as for any therapeutic or diagnostic agent used, the toxic potential of the CNTs must be evaluated in relation to their potential benefits [160]. For this reason, detailed investigations of the interactions between CNTs/CNT-based implants and various cell types have been carried out [154, 155, 161]. A comprehensive description of such results, however, is beyond the scope of this chapter. Extensive reviews on the biocompatibility of implantable CNT composite materials [21, 143, 162] and of CNT drug-delivery systems [162] are available. 

Akagi et al. demonstrated the use of nanoparticles composed of amphiphilic poly (amino acid) derivatives as vaccine delivery and adjuvants [62, 102-104]. To evaluate the uptake of OVA encapsulated within y-PGA-Phe nanoparticles (OVA-NPs) by DCs, murine bone marrow-derived DCs were incubated with 250 nm-sized OVA-NPs for 30 min at 37 °C. The cells were then analyzed by flow cytometry (FCM) and confocal laser scanning microscopy (CLSM). OVA-NPs were efficiently taken up into DCs, whereas the uptake of OVA alone was barely detectable at the same concentration of OVA (Fig. 13). OVA-NPs were more efficiently taken up than OVA alone by DCs, and the uptake of OVA-NPs was inhibited at 4 °C. These results suggest that OVA-NPs were phagocytosed mainly via endocytosis by the DCs. In the case of OVA alone, an approximately 30-fold... 

O Hagan DT, Rappuoli R (2004) Novel approaches to vaccine delivery. Pharm Res 21 1519-1530... 

Peek LJ, Middaugh CR, Berkland C (2008) Nanotechnology in vaccine delivery. Adv Drug Deliv Rev 60 915-928... 

Jilek S, Merkle HP, Walter E (2005) DNA-loaded biodegradable microparticles as vaccine delivery systems and their interaction with dendritic cells. Adv Drug Deliv Rev 57 377-390... 

Wendorf J, Chesko J, Kazzaz J et al (2008) A comparison of anionic nanoparticles and microparticles as vaccine delivery systems. Hum Vaccin 4 44-49... 

Chong CS, Cao M, Wong WW et al (2005) Enhancement of T helper type 1 immune responses against hepatitis B virus core antigen by PLGA nanoparticle vaccine delivery. J Control Release 102 85-99... 

Eldridge, J.H. et al., Biodegradable Microspheres as a Vaccine Delivery System, Molecular Immunology. 28, 287, 1991. 

Amselem, S., C.R. Alving, A.J. Domb, Polymeric Biodegradable Lipospheres as Vaccine Delivery Systems, Polymers for Advanced Technologies, 3, 351, 1992. 

This chapter will describe the potential of carbon nanotubes in biomedicine. It will illustrate the methodologies to render nanotubes biocompatible, the studies on their cell uptake, their application in vaccine delivery, their interaction with nucleic acids and their impact on health. 

J. Singh, S. Pandit, V. W. Bramwell, and H. O. Alpar. Diphtheria toxoid loaded poly-(e-caprolactone) nanoparticles as mucosal vaccine delivery systems. Methods 38 96-105 (2006). 

Finally, besides conventional liposomes that are made from natural (e.g., egg yolk and soybean) or synthetic phospholipids, novel liposomes called archaeosomes that are prepared from the polar ether lipids extracted from various archaeobacteria proved also interesting for the design of vaccines as peptide antigen carriers (71) and as powerful self-adjuvanting vaccine delivery vesicles that promote both humoral and cell-mediated immunity (72). Related to this, one can mention that pseudopeptides, which are less prone to proteolysis when conjugated to liposomes, were also competent in triggering a humoral immune response (73). 

ITABLE 11.3. Novel adjuvant systems and vaccine delivery technologies... 

Although Vaccinia was eliminated from the international scene as recently as two decades ago, terrorism fears have generated renewed interest in the large-scale protection of an unprotected population against the disease, which has occasionally reappeared as a result of laboratory accidents and, in some cases, of deliberate dissemination of the virus. This is one example of the primary need for protection against the disease and for suitable vaccine delivery systems. 

---