Evolution of Nanocarrier Drug-Delivery Systems and Recent Advancements in Covalent Organic Framework-Drug Systems

Nanotechnology has been actively employed in the development of drug-delivery systems overcoming the limitations of conventional carriers. In nanomedicine, the ultimate goal is to design and develop a system for the prevention, diagnosis, control, and treatment of debilitating diseases. Nanoparticles can be designed and programmed to have unique physical properties, in order to protect the loaded drug against degradation and/or denaturation by natural processes inside the body, while selectively delivering it to target areas having the desired cells. This effectively minimizes the active pharmaceutical ingredient's (API's) systemic exposure and, consequently, the occurrence of adverse side effects. The enhanced control on the distribution and release of the entrapped drug molecules, through active targeting and controlled-release technology, allows for their increased and accurate cellular uptake. In this review, we summarize the development of nanobased drug-delivery systems, with a focus on smart systems and the necessary characteristics required for the optimal drug nanocarrier. The recently developed class of crystalline porous polymers, covalent organic frameworks (COFs), possesses a unique combination of characteristics including permanent yet tunable discrete pores having high surface areas and large volumes, making them intrinsically designed to accommodate APIs as guest molecules in their highly ordered pores. The extensive synthetic and molecular design flexibility of COFs allows the structural control and tuning of their morphology, regularity, atomic connectivity, and porosity, for this specific application. Through an overview of the recent advancements in the novel application of metal- organic frameworks (MOFs) and COFs as drug nanocarriers, we demonstrate this promising alternative route to effectively increase the drug solubility and enhance the limited loading capacity and release control of nanoparticle systems. Since the first reported COF nanocarriers in 2011 as passive targeting drug-delivery systems, this application of COFs has been slowly gaining traction, with increasingly complex COF nanocarrier drug-delivery systems reported in the past year.