Smart biomaterials for precision drug delivery: emerging strategies for site-specific targeting and controlled therapeutic release

Conventional drug delivery is constrained by several factors such as rapid distribution and elimination in the body, a narrow range of effective doses, and the inability of the system to adjust according to the situation of the disease. Smart biomaterials such as natural biomaterials (polysaccharides, proteins, and peptides), synthetic biomaterials (PLGA, PLA, dendrimers, and hydrogels), and hybrid lipid–polymer or organic–inorganic systems can provide a solution to these challenges by being the first active, responsive, stimuli, and controlled release carriers for targeted delivery. This review outlines the progress and development of smart biomaterials and their use in drug delivery. We will analyze the use of passive (enhanced permeability and retention (EPR)-driven) and active (ligand receptor) targeting, address the barriers to drug delivery in the body, and examine the impact of physical properties such as size, shape, and surface chemistry on delivery systems. For this review, we will also examine the available major classes of drug delivery nanocarriers and responsive systems that are triggered by pH, redox, enzymes, temperature, light, ultrasound, and magnetism. We will also consider new technologies such as intelligent systems, digital twins, organ-on-a-chip, microfluid robotics, and nanorobots, which are revolutionizing the drug delivery design process from non-systematic to systematic and aligned. With a focus on drug delivery designs that are aimed for use in practice, we will examine available drug delivery systems and discuss the toxicity of nanosystems, variability with respect to biology, the framework of design standards, and other relevant systems. We will deliver our opinion that the available drug delivery systems, when integrated with the use of biomarkers, will provide the most benefit.