Protozoan variant-specific surface proteins (VSP) as carriers for oral drug delivery

摘要

The invention provides compositions for oral delivery and methods of treatment using VSP carriers, such as Giardia sp. variable surface proteins (VSP), to deliver therapeutic agents. VSP drug carriers can be combined with bioactive peptides, e.g., insulin, glucagon, or hGH, and be administered orally or mucosally. VSP carriers are resistant to acidic pHs and to proteolytic degradation and protect therapeutic agents from degradation in the gastrointestinal tract.

主权项

1. A therapeutic composition comprising a VSP (Variant-specific Surface Protein) carrier and a bioactive peptide, wherein
(i) the VSP carrier can bind to the bioactive peptide; (ii) the VSP carrier is not covalently bound to the bioactive peptide via a peptidic bond; (iii) the bioactive peptide is therapeutically effective after binding to the VSP carrier; (iv) the binding of the VSP carrier to the bioactive peptide increases the resistance of the bioactive peptide to pH-mediated and/or enzymatic degradation compared to the resistance of the same bioactive peptide not bound to said VSP carrier; (v) the bioactive peptide is selected from the group consisting of insulin, human growth hormone, and glucagon; (vi) the bioactive peptide is not a vaccine immunogen, and (vii) the VSP carrier has at least 70% amino acid sequence identity with the sequence of the extracellular domain of a VSP from Giardia selected from VSP1267 (SEQ ID NO: 490), VSP9B10 (SEQ ID NO: 572), and VSPH7 (SEQ ID NO:504).