VSPs of G. lamblia as carriers in chronic oral administration of peptide drugs

MARTINO RA; OMS SR; RIOS DN; SERRADELL MC; LUJAN HD

Córdoba

Congreso; 52 th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2016

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Despite the relevance of proteins and peptides as therapeutic agents, very few are available for oral administration. Acid hydrolysis in the stomach due to low pH, luminal degradation in the intestine by different proteases and variability in absorption are the major factors that prevent bioactive peptide administration by the oral route. We here show that different Variant-specific Surface Proteins (VSPs) of the intestinal parasite Giardia lamblia can be used as carrier for oral peptide delivery. The extracellular domains of different VSPs (ΔVSPs), which contain multiple CXXC motifs, were produced in an insect cell expression system. Like native Giardia VSPs, recombinant ΔVSPs are resistant to acidic pH and proteolytic degradation and adhere to the intestinal mucosa. Chronic administration of IFNα and glucagon, as prototype drugs, in combination with ΔVSPs derived from different Giardia assemblages showed that ΔVSPs protect these bioactive peptides from degradation and promote their systemic biological action. These results demonstrate that VSPs are attractive candidates for oral administration of peptides for the treatment of chronic diseases.