RECENT ADVANCEMENTS IN PRODRUG DESIGN: STRATEGIES, CHALLANGES AND FUTURE PERSPECTIVES

Palak Kumari*

ABSTRACT

Prodrug design has emerged as a critical strategy in modern drug development, addressing challenges such as poor solubility, low bioavailability, rapid metabolism, and systemic toxicity. By incorporating chemical modifications, prodrugs undergo biotransformation to release the active drug at the intended site of action, improving therapeutic efficacy and patient compliance. Recent advancements in prodrug design have introduced enzyme-activated, site-specific, nanotechnology-based, and stimuli-responsive prodrugs, significantly enhancing drug delivery mechanisms. This review explores the latest strategies in prodrug development, highlighting key approaches such as enzyme-activated prodrugs, tumor-targeted prodrugs, and nanocarrier-based delivery systems. The integration of artificial intelligence (AI), computational modeling, and pharmacogenomics is paving the way for personalized prodrug therapies, optimizing activation mechanisms and minimizing adverse effects. Furthermore, emerging trends such as CRISPR-based gene-directed prodrug activation, AI-driven drug discovery, and stimuli-responsive nanoprodrugs are expected to revolutionize the field. Despite the challenges, the future of prodrug research holds immense potential, with interdisciplinary collaboration driving innovations toward safer and more effective therapies. The continued evolution of smart prodrugs and regulatory advancements will be instrumental in accelerating the clinical translation of next-generation prodrugs, ultimately improving patient outcomes across various therapeutic domains.

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