Ionic liquid combined with bile acid pathway for oral delivery of rhGH

Abstract

Abstract Oral absorption and room temperature storage remain two major challenges limiting the bioavailability of recombinant human growth hormone (rhGH) due to the need to overcome the unfavorable gastrointestinal environment and resist temperature effects on rhGH structure, Therefore, we designed a multifunctional nanoplatform to address both problems simultaneously. The carrier consists of PLGA, ionic liquid (IL) and deoxycholic acid (DCA). In this nanosystem, IL acts as a green non-toxic solvent and helps the nanoparticles to open tight junctions between cells, and acts as a room temperature protectant to improve the room temperature stability of rhGH. Endogenous DCA as a ligand increases intestinal absorption of nanoparticles through receptor-mediated endocytosis. The nanoparticles have the following advantages: 1) Protects rhGH in the gastrointestinal tract from being degraded by gastric acid and proteases. 2) The absorption of rhGH in intestinal tract was increased and its bioavailability was enhanced. 3) The storage time of rhGH at room temperature was prolonged. These materials are cheap, readily available and easily synthesized and these studies provide a basis for the clinical application of rhGH.