Platform Technology for Efficient Oral Administration of Peptides for Therapeutic Purposes

Gilon Chaim, HUJI, Faculty of Science, The Institute of Chemistry
Hoffman Amnon, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research


  • Peptides are key players in a variety of physiological and pathological processes and play very important roles in modulating various cell functions.
  • One of the most important challenges developing peptide drugs is the lack of appropriate physicochemical properties that enables the absorption through biological membranes.
  • Currently, most peptide drugs are administered parentally due to their poor intestinal permeability attributed to their  hydrophilicity mainly due to charged groups.

Our Innovation

  • A novel method called Lipophilic Prodrug Charge Masking (LPCM) that enhance the intestinal permeability and the oral bioavailability of charged peptides
  • Significantly increased permeability rate of most peptides compared to the respective unmasked peptides.
  • Brings into the systemic blood circulation the parent drug.
  • Converts active peptides to orally therapeutic treatment


  • The major challenges in peptide membrane permeability via passive diffusion include the peptide’s high polarity, charge and hydrogen bond potential.
  • In the LPCM method, synthetic methods for the conversion of peptides, peptidomimetic and peptide drugs into their lipophilic prodrug were demonstrated.
  • Charged masked peptide prodrugs were synthesized and masked with urethane/ ester type lipophilic pro-moiety.  The prodrug enhanced intestinal permeability allowed its absorption to the blood stream where esterases removed the pro-moiety to regenerate the original peptides.
  • The LPCM method shifts the mechanism of intestinal permeability of the charged peptides from para-cellular to trans-cellular pathway of their lipophilic prodrug 


Fig. 1: Principle of the LPCM method



  • New oral peptides/peptidomimetics medications
  • Chronic treatment with good patient compliance
  • Currently being studied  and tested for RGD containing peptide


Patent Status

Published US 2022/0016218 A1; US 2020/0283483 A1

Contact for more information:

Keren-Or Amar
VP, Business Development, Healthcare
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