Next-generation long-acting injectables: Technological innovations and patient-centric design in complex drug delivery systems

Long-acting injectables (LAIs) have transformed drug delivery by enabling sustained and controlled release of therapeutics, which can improve treatment efficacy, patient adherence, and dosing convenience. However, traditional depot systems such as polymeric microspheres and oil-based formulations still face several limitations like burst release, complicated manufacturing procedures, and stability concerns, particularly when delivering peptides and biologics. Existing reviews often focus on individual material classes or isolated formulation approaches, leaving a fragmented understanding of the broader field. This review aims to bridge that gap by bringing together recent advances in formulation design with developments in predictive modelling, advanced analytical characterization, and translational considerations for complex LAI systems. We highlight recent innovations in molecular and polymer engineering, in situ depot systems, and real-time depot monitoring, emphasizing how these advances can overcome conventional challenges and support clinical translation. By linking formulation science with translational perspectives, this review offers an integrated overview and outlines future directions for the development of safer and more effective long-acting therapeutic platforms.