Tesiak

USE OF MICROPARTICULAR SYSTEMS AS ADJUVANTS OF SYNTHETIC ANTIMALARIC ANTIGENS.

Doktoregaia:
Elena Mata Gomez de Segura
Urtea:
2013
Unibertsitatea:
Faculty of Pharmacy. University of the Basque Country
Zuzendaria(k):
ROSA HERNANDEZ Y MANUELA IGARTUA
Deskribapena:

This work includes the application of microparticular systems as a vehicle/adjuvant of synthetic antimalarial antigens to enhance and modulate their immunogenicity. In the first place, different anti-malarial synthetic peptides were microencapsulated and the developed formulations were characterized; in addition, the immune response induced by these antigens formulated in microparticles of PLGA were evaluated and compared to their transport with another particulate adjuvant, Montanide. The effect of modifying these micropaticular systems, such as incorporating alginate into the polymer matrix or including RGD sequences on the surface, on their immunopotentiating and immuno-modulatory capacity was also evaluated, and the results showed that both microparticles of PLFA and Montanide administered via sc have a similar ability to stimulate IgG antibody responses and their subclasses. However, although the functionality of these antibodies is superior in the case of microparticles and although the Montanide enhances Th2 (Total and non-specific IgE) response, the latter in turn induces a superior cellular response. On the other hand, the immunization id with PLGA microparticles improves the immune response achieved by sc. And it surpasses Montanide in terms of both antibody secretion, including cytophilic antibodies, and cellular response. In addition, the incorporation of alginate in the polymer matrix of PLGA microparticles induces potentiation and immunomodulation of the immune response typoi Th1. Finally, the inclusion of RGD sequences on the surface of microparticles results in efficient vectorization towards antigen-presenting cells, improves their uptake and promotes the induction of cellular responses.

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