Multiple emulsions vaccines

Other drug-delivery systems may include double emulsions, usually W/O/W, for transporting hydrophilic dmgs such as vaccines, vitamins, enzymes, hormones [441], The multiple emulsion also allows for slow release of the delivered drug and the time-release mechanism can be varied by adjusting the emulsion stability. Conversely, in detoxification (overdose) treatments, the active substance migrates from the outside to the inner phase. 

Chitosan microspheres act as promising carriers for oral pDNA vaccine in comparison with fish vaccinated with naked pDNA A relative percent survival (RPS) rate of 46% was recorded. Sea bass (Lales calcarifer) orally vaccinated with chitosan-DNA (pVAOMP38) complex showed moderate protection against experimental V. anguillarum infection Squalane oil-containing W/O/W multiple emulsion formulations can significantly enhance the local and systemic immune responses, especially after oral administration... 

Multiple emulsions have been utilized as adjuvants for the delivery of vaccines (Herbert, 1965 Aitken, 1973 Blackall et al, 1992). The incorporation of ovalbumin or other foreign protein has been found to result in higher and more sustained antibody titers compared to those obtained with administration of vaccines in saline solutions. 

Multiple emulsions are complex systems wherein droplets of (he dispersed phase contain additional but smaller droplets, identical to or different from the continuous phase. Even so there are many interesting fields of potential research and applications, such as vaccine formulations, enzyme immobilization, and drug overdose treatment (122). Ttie disadvantages of current multiple emulsions are obvious. Internal droplet growth and release as well as degradation to heterogeneous O/W or W/O formulations results in shear sensitivity and bad long-term multiplicities. Besides, those systems are problematic to produce al industrial scale. 

Water-in-oil solubilized adjuvant formulations of vaccines containing Clostridium welchii type D toxoid as antigen were prepared first in 1968 and tested in laboratory animals by Coles et al [238]. The adjuvant action of oil-in-water emulsions, multiple emulsions and water in gelled oil emulsions is well known but these varied systems have the disadvantages of high viscosity which makes injection physically difficult. Lin [236] quotes an HLB of 9.7 as the optimum value for water solubilization in mineral oil. Coles et al [238] found a value of 10. While the addition of a small quantity of the lipophilic surfactant Arlacel 80 (sorbitan mono-oleate) to a system of Tween 81 (polyoxyethylene (5)-sorbiton mono-oleate) alio wed increasing amounts of water to be solubilized, when toxoid solution was substituted for water the Arlacel decreased the amount which could... 

Taylor et al, [253] extended the use of W/O/W vaccines to man and compared antibody levels and short-term reactions after administration of influenza vaccine in aqueous, W/O and W/O/W formulations. The W/O/W preparation was at least as effective as the W/O preparation. Short-term reactions to the multiple emulsion were more frequent than those associated with the aqueous and W/O preparations but these were found to be mild and the authors did not consider them to constitute a serious drawback to a more extensive use of the vaccine. 

Many compounds with adjuvant activity are presently known (shown in Table 12.2) but only a few are applied routinely in human and veterinary vaccines. The application of the novel adjuvants are limited for several reasons, such as disappointing efficacy in the target animal species, insufficient safety, problems with large-scale preparations, and limited stability of the final formulations. Many studies have reported on O/W and W/O emulsions used as adjuvants and delivery systems for immunization (Hilgers et al., 1994a, b, 1999). The adjuvanticity of the W/O/W makes this type of multiple emulsion a suitable delivery system for immunization with prolonged release, and its interesting preparation is presented below. 

Multiple emulsions have been widely studied as means of delivering drugs via oral, topical, and parenteral routes. The applications include protein delivery (Cournarie et al., 2004), delivery of antibiotics to the vagina (Tedajo et al., 2005), sustained delivery (Vaziri and Warburton, 1994), and vaccine delivery (Bozkir and Hayta, 2004). The immunological response to a vaccine also depends on the route of administration. Most current vaccines are administered intramuscularly, which induces immunization as a systemic immunity. However, the live polio vaccine and the live typhoid vaccine are administered orally. Local immunization (oral, intranasal, or intravagina) may be preferred, since mucosal surfaces are the common entrance to many pathogens. Moreover local immunization induces both mucosal and systemic immunity. Ease of administration and avoidance of systemic side effects are additional advantages of local immunization (Walker, 1994 Shalaby, 1995). Nevertheless, successful local immunization has only been achieved with a limited number of oral vaccines. Also there are very few studies on multiple emulsions used in the immunization process, especially on parenteral and oral administration. 

Comparisons of antigen carrier systems have been the subject of many studies. The reported antigenic activity depends on the properties of the carrier systems such as their adjuvant effect and/or particle size, and viscosity. For a comparison to be valid, the systems being compared must show similar properties otherwise, the studies are misleading. Based on their properties, already it is evident that emulsion and liposome formulations offer more advantageous results. In our studies we found that multiple emulsions induce more antigenic activity than any cationic particle formulation with the classic subunit vaccine, and they enhance the immunization s efficacy (Bozkir et al, 2004). 

Hearn TL, Olsen M, Hunter RL. 1996. Multiple emulsions oral vaccine vehicles for inducing immnnity or tolerance. An NY Acad Sci 778 388-389. 

Finally, A. Bozkir and O. M. Saka review the use of multiple emulsions as carriers for delivery systems for antigens and vaccines. 

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