Abstract
Due to the poor physicochemical properties of drugs and multi-stage biological barriers in vivo, drugs at action site cannot reach up to sufficient concentration to acquire expected therapeutic outcomes, which may conversely lead to side effects to normal tissues and organs. In recent years, nanoscale drug delivery systems (NDDS) have developed rapidly to effectively deliver drugs to target site. In addition to avoiding drug degradation and preserving drug physicochemical properties, NDDS with controllable drug behaviors on tissues, cells, and organelles can be applied to break through multi-stage barriers and manipulate drug metabolism. But poor knowledge of various biological barriers still hinders the development of NDDS. Hence, this review is to dissect the vital influence of biological barriers in pharmaceutical research and introduce strategies for manipulating drug behaviors by crossing multi-stage biological barriers. Moreover, setbacks faced in the development of nanotechnology-based formulations are analyzed, which brings systematic thinking in the field of drug delivery. By addressing these barriers and understanding the principles behind, the current review provides a new insight into the rational design of NDDS and promotes the development of nanomedicine.
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