Self-Destructing Drug Delivery Systems: Design, Mechanisms and Clinical Translation
DOI:
https://doi.org/10.22159/ijap.2026v18i5.58412Keywords:
Self-destructing drug delivery systems, Stimuli-responsive nanocarriers, Biodegradable polymers, Enzyme-sensitive systems, Controlled drug release, Smart drug deliveryAbstract
To critically evaluate the design principles, mechanisms, and clinical translation potential of self-destructing drug delivery systems (SDDDS) as advanced platforms for overcoming the limitations of conventional drug delivery, including prolonged carrier retention, off-target toxicity, and poor control over drug release. A comprehensive and systematic review of recent literature (primarily 2020–2025) was conducted, focusing on the structural design, material selection, and stimuli-responsive self-destruction mechanisms of SDDDS. Preclinical and early clinical studies were analyzed to assess pharmacokinetics, biodegradation behaviour, and safety profiles. Additionally, key translational challenges, including physiological variability, large-scale manufacturing constraints, and regulatory considerations, were critically examined. Self-destructing drug delivery systems demonstrated significant advantages over conventional carriers by enabling controlled, stimuli-triggered drug release followed by programmed structural disintegration and rapid clearance. These systems effectively reduced long-term carrier accumulation and associated toxicity while improving therapeutic precision. Stimuli-responsive mechanisms such as pH-, redox-, enzyme-, and light-triggered degradation were identified as critical contributors to system performance. Emerging platforms, including stimuli-responsive liposomes and redox-cleavable polymeric nanoparticles, showed promising preclinical outcomes and early clinical translation potential, particularly in oncology applications. SDDDS represent a transformative advancement in smart drug delivery, integrating controlled drug release with post-therapeutic self-elimination to enhance safety and efficacy. Despite promising progress, challenges related to stability, scalability, and regulatory approval remain. Continued advancements in material engineering, personalized medicine approaches, and multifunctional system design are expected to accelerate clinical translation and establish SDDDS as a key component of next-generation therapeutics.
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