Summary of the technology
Synthesis of Cyclic Peptidomimetics and their Prodrugs for oral delivery
Project ID : 6-2017-4503
Description of the technology
Platform technology, Intestinal permeability, Lipophilic Prodrug Charge Masking, peptides, oral bioavailability
Current development stage
TRL4 - POC & Safety of candidate drug formulation is demonstrated in defined animal model
- 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.
- 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 studiedand tested for RGD containing peptide