Hydrogel-Based Smart Drug Delivery Systems: Injectable and Implantable Platforms

Abstract

Hydrogel-based smart drug delivery systems have emerged as one of the most transformative platforms in modern pharmaceutics, offering unique advantages in terms of biocompatibility, tunable physicochemical properties, and the ability to respond to environmental or physiological stimuli. Injectable and implantable hydrogels have particularly gained attention for their capacity to provide localized, controlled, and sustained release of therapeutic agents, reducing systemic toxicity and improving patient compliance. Hydrogels mimic the extracellular matrix, providing a hydrated three-dimensional environment suitable for drug encapsulation, protection, and on-demand release. Stimuli-responsive hydrogels that react to pH, temperature, redox state, enzymes, and external triggers such as light, ultrasound, or magnetic fields further expand their applications in cancer therapy, regenerative medicine, diabetes management, and infectious disease control. Injectable hydrogels enable minimally invasive administration, in situ gelation, and conformability to irregular tissue defects, while implantable hydrogels offer durable depots for long-term delivery, particularly for hormones, analgesics, anticancer agents, and vaccines. Recent advances in hybrid hydrogels incorporating nanomaterials, bioactive molecules, and 3D printing have broadened their therapeutic potential. However, challenges related to long-term biostability, sterilization, large-scale manufacturing, and regulatory approval remain. This review critically examines the design principles, stimuli-responsiveness, therapeutic applications, and translational challenges of injectable and implantable hydrogel-based smart drug delivery systems, highlighting current clinical progress and future perspectives.