Among the drug delivery methods, oral administration is a simple and painless method. However, oral delivery of protein drugs has defects in their application. Low absorption rate in the gastrointestinal tract (GIT) caused by the physical barriers of intestinal epithelia is the most difficult challenge to overcome. Transcytotic ligand TP1 was found in our laboratory through peroral phage display technique, which was characterized as having a transcytotic property to traverse intestinal epithelia by targeting goblet cells. We demonstrated that TP1 enhanced the efficiency of protein drug delivery via oral route as a form of ;;Conjugated drug’. We generated a model drug which was composed with TP1 and human growth hormone (hGH) by genetic recombination. The conjugated drug was produced from Pichia pastoris as a mass-production system and purified by hydrophobic interaction chromatography (HIC). The function of this recombinant protein drug were validated by in vitro and in vivo assays. This recombinant drug showed transcytotic property to intestinal epithelia as well as revealed its own activity as growth hormone. And it increased growth performance in tested animals compared to non-treated group. We also found that only TP1 introduced in C-terminus of hGH could maintain its transcytotic property as an oral drug. The present study opens up the possibility for the establishment of an effective oral drug delivery system using transcytotic peptide, TP1, could be applied in the pharmaceutics and animal industry fields to improve availability of protein drugs via oral route.
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Production of recombinant human growth hormone with a transcytotic peptide in Pichia pastoris and its functional validation via oral administration
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