Prodrug Approach as a Strategy to Enhance Drug Permeability.

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Drug Delivery

Background:

• Drug absorption and permeability are critical physicochemical parameters for optimal drug uptake and achieving therapeutic plasma levels.
• Prodrugs are inactive compounds that release active drugs via bio-reversible processes, offering a versatile strategy to improve drug properties.
• Approximately 13% of FDA-approved drugs between 2012-2022 were prodrugs, highlighting their significance in pharmaceutical development.

Purpose of the Study:

• To review the application of prodrug strategies for enhancing drug permeability.
• To explore the use of prodrugs in optimizing the permeability of PROteolysis TArgeting Chimeras (PROTACs).
• To highlight novel prodrug technologies for improving permeability and developing safer, more effective drugs.

Main Methods:

• Review of existing literature on prodrug design and applications.
• Analysis of market-approved drugs utilizing prodrug strategies for permeability enhancement.
• Examination of conjugation technologies for optimizing PROTACs permeability via prodrug approaches.

Main Results:

• Prodrug strategies significantly improve physicochemical properties, biopharmaceutical, and pharmacokinetic parameters of drugs.
• Prodrugs have been successfully implemented in various marketed drugs to enhance absorption and permeability.
• Emerging prodrug technologies show promise for further optimizing permeability and drug efficacy.

Conclusions:

• Prodrug design is a highly effective and versatile approach for optimizing drug uptake and therapeutic outcomes.
• The prodrug strategy is crucial for advancing drug development, including novel modalities like PROTACs.
• Continued innovation in prodrug technologies will lead to the development of more effective and safer therapeutic agents.