Surface molecules of Giardia lamblia protects bioactive peptides for oral administration

ROMAN A. MARTINO, MARIANELA C. SERRADELL, MA. CECILIA GAGGIOTTI, HUGO D. LUJÁN

Mendoza

Encuentro; XLVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Giardia is an intestinal pathogen that undergoes antigenic variation, a mechanism by which trophozoites continuously switch its major surface molecules. These surface antigens belong to a family of cysteine-rich Variant-specific Surface Proteins (VSPs), which are integral membrane proteins that cover the entire surface of trophozoites for protection within the upper small intestine. VSPs present unique characteristics that make them ideal candidates to transport drugs through the gastro intestinal track: they are resistant to acidic pH and proteolytic degradation and adhere to the intestinal mucosa. As a proof-of-principle, we initially used insulin as a prototype drug to be delivered by the oral route. We tested if the combination of insulin with a VSP can protect this molecule from degradation and promote its systemic biological action. We also tested bioactive peptides in their capacity to remain active after being mixed with a VSP and treated with different proteolytic enzymes or confronted to acidic pH both in vitro and in vivo. For the generation of the extracellular portion of the VSPs, we selected the Baculovirus Expression System using a proprietary purification approach. Our results showed that Giardia VSPs protect bioactive peptides when administered by the oral route. The structural characteristics of the VSPs that confer these properties are under analysis.