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Structure modification: a successful tool for prodrug design

    Yuexuan Cheng‡

    College of Pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Chunhong Zhong‡

    College of Pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Shujing Yan

    College of Pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China

    ,
    Chunli Chen

    College of Pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China

    Engineering Research Center of Xinjiang & Central Asian Medicine Resources, Ministry of Education, Urumqi, Xinjiang, 830011, China

    &
    Xiaoli Gao

    *Author for correspondence: +86 136 099 05058;

    E-mail Address: xli_g@sina.com

    College of Pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China

    Engineering Research Center of Xinjiang & Central Asian Medicine Resources, Ministry of Education, Urumqi, Xinjiang, 830011, China

    Published Online:https://doi.org/10.4155/fmc-2022-0309

    Prodrug strategy is critical for innovative drug development. Structural modification is the most straightforward and effective method to develop prodrugs. Improving drug defects and optimizing the physical and chemical properties of a drug, such as lipophilicity and water solubility, changing the way of administration can be achieved through specific structural modification. Designing prodrugs by linking microenvironment-responsive groups to the prototype drugs is of great help in enhancing drug targeting. In the meantime, making connections between prodrugs and suitable drug delivery systems could realize drug loading increases, greater stability, bioavailability and drug release control. In this paper, lipidic, water-soluble, pH-responsive, redox-sensitive and enzyme-activatable prodrugs are reviewed on the basis of structural modification.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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