Recent Advances in Prodrug Design: Chemical Strategies and Pharmaceutical Applications

As a crucial molecular modification strategy, prodrugs enable the release of active pharmaceutical ingredients through enzymatic or chemical reactions within the body, thereby playing a pivotal role in enhancing drug solubility, stability, bioavailability, and safety. With advances in medicinal chemistry, nanotechnology, and biomedicine, prodrug research has expanded beyond mere physicochemical optimization to encompass targeted therapy and personalized medicine. This paper systematically reviews the fundamental principles, classification, primary applications, development challenges, and future directions of prodrugs. It highlights emerging trends such as drug-auxiliary prodrugs, microenvironment-responsive prodrugs, AI-assisted design, and enzyme-mediated prodrug therapies.