Variant-specific Surface Proteins from Giardia lamblia as a new tool for oral drug delivery

SERRADELL MARIANELA C; MARTINO ROMAN A; RUPIL LUCIA; GARGANTINI PABLO RUBÉN; SAURA ALICIA; LUJAN HUGO D

Rosario

Congreso; L Reunión anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2014

Oral administration is an ideal mean for providing therapeutic agents due to its painless administration, patient compliance and low cost. However, it is also the most difficult approach because of the gastrointestinal tract properties, such as extremely low pH in the stomach and enzymatic degradation in the upper intestine. Here we show that Variant-specific Surface Proteins (VSPs) of the intestinal parasite Giardia lamblia can be used as carrier for oral delivery of drugs. VSPs cover and protect the parasite from the harsh conditions of the upper small intestine. The extracellular region (ExR) of VSPs is rich in cysteine, mostly as CXXC motifs. Recombinant VSP ExRs produced in insect cells, similarly to native VSPs, are resistant to acidic pH and proteolytic degradation and adhere for hours to the intestinal mucosa. We initially used insulin and glucagon in combination with VSP ExRs as prototype drugs. Results in mice showed that VSP´s ExRs protect these bioactive peptides from degradation and promote their systemic biological action, namely the regulation of blood glucose levels. VSP ExRs were also able to protect other peptides, such as growth hormone, IL-10 and IFN, both in vitro and in vivo, significantly assisting their oral absorption. Results demonstrate that combination of the ExR of VSPs with bioactive peptides is a promising approach for oral administration of drugs.