a comprehensive review of drug targeting strategies in advanced delivery systems

Despite notable progress in drug delivery research, many therapeutic agents still fail to achieve precise target localization, leading to limited bioavailability, systemic toxicity, and reduced clinical efficacy. this review introduces a comparative mechanistic framework that categorizes drug targeting strategies based on their biological foundation (passive and active mechanisms) and functional sophistication (physical, inverse, dual, and double targeting). moreover, it provides a critical evaluation of how each approach addresses major barriers in drug delivery, such as biological heterogeneity, off-target drug accumulation, and molecular instability, through distinct physicochemical and molecular design principles. the review also highlights emerging trends that integrate nanotechnology with biological targeting, including stimuli-responsive nanocarriers, multi-ligand conjugates, and receptor–microenvironment dual targeting. by synthesizing these advancements, it establishes a hierarchical conceptual model linking targeting mechanisms, carrier design, and translational feasibility, thereby offering a structured framework for innovation. ultimately, this review provides an integrated perspective that consolidates existing drug targeting paradigms and defines a mechanistic roadmap for designing next-generation delivery systems, offering researchers and clinicians a foundation for developing more precise, adaptive, and patient-tailored therapies.