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

MARTINO ROMAN; SERRADELL MARIANELA C; RIOS DIEGO N.; OMS SERGIO; LUJAN HUGO DANIEL

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; 2016

SAIB

Despite the relevance ofproteins and peptides as therapeutic agents, very few are available for oraladministration. Acid hydrolysis in the stomach due to low pH, luminaldegradation in the intestine by different proteases and variability inabsorption are the major factors that prevent bioactive peptide administrationby the oral route. We here show that different Variant-specific SurfaceProteins (VSPs) of the intestinal parasite Giardia lamblia can be usedas carrier for oral peptide delivery. The extracellular domains of differentVSPs (ÄVSPs), whichcontain multiple CXXC motifs, were produced in an insect cell expressionsystem. Like native Giardia VSPs, recombinant ÄVSPs are resistant toacidic pH and proteolytic degradation and adhere to the intestinal mucosa.Chronic administration of IFNá and glucagon, as prototype drugs, in combinationwith ÄVSPs derivedfrom different Giardia assemblages showed that ÄVSPs protect thesebioactive peptides from degradation and promote their systemic biological action.These results demonstrate that VSPs are attractive candidates for oraladministration of peptides for the treatment of chronic diseases.