Bioadhesive nanoparticles for oral antigen delivery

• Autores: Salman Hesham
• Directores de la Tesis: Juan Manuel Irache Garreta (dir. tes.), Carlos Gamazo (codir. tes.)
• Lectura: En la Universidad de Navarra ( España ) en 2006
• Idioma: español
• Tribunal Calificador de la Tesis: Ignacio Moriyón Uría (presid.), María José Blanco Prieto (secret.), Emma E. McGinty (voc.), Luis Miguel Ortega Mora (voc.), Chris de Smidt (voc.)
• Materias:
  • Ciencias de la vida
    • Inmunología
      • Vacunas
  • Ciencias médicas
    • Farmacodinámica
      • Absorción de medicamentos
    • Farmacología
      • Composición de medicamentos
      • Evaluación de medicamentos
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• Resumen

  • TITUL0: BIOADHESIVE NANOPARTICLES FOR ORAL ANTIGEN DELIVERY #RESUMEN: Oral route of administration is the most convenient one for vaccination and immunotherapy. However, many peptides, proteins or DNA vaccines are of low oral stability and bioavailability. Thus, nanoparticles have the advantageous ability to protect the encapsulated antigens from the gut degradation. Unfortunately, conventional nanoparticles do not have the ability to target specific tissues of the gastrointestinal tract (e.g., enterocytes or Peyer's patches), limiting their success as oral antigen delivery systems. in order to overeóme this drawback, this thesis deals with the design of specific bioadhesive nanoparticles by the association of Gantrez AN nanoparticles and specific cytoadhesive ligands (Flagellin from Salmonella Enteritidis, mannosamine, vitamin B12-NH2 derivative, and thiamine). The adjuvant capacity of these systems after oral antigen delivery was investigated using ovalbumin. The results of oral administration indicated that these modified nanoparticles displayed a stronger bioadhesive capacity and high affinity to Peyer's patches within the gut of laboratory animal. The oral immunization with ovalbumin loaded in these nanoparticles induced higher and more balanced [Thl (igG2a) and Th2 (igGl)] systemic immune responses than that noted for control unmodified nanoparticles. In addition, the new formulations enhanced the mucosal immune response (intestinal igA). In summary, this work demonstrates the advantages of ligand-nanoparticle conjugates in oral antigen delivery, which would encourage their application in oral vaccination and immunotherapy strategies