The history of gated drug delivery systems starts in the mid-1960s when the concept of zero order controlled drug delivery was first thought of. Researchers raced to be able to find a drug delivery platform that would be able to have perfectly sustained drug release. These efforts were initially on the macroscopic level with some of the first controlled drug delivery (CDD) devices being an ophthalmic insert, an intrauterine device, and a skin patch. In the 1970s the drug delivery field shifted from macroscopic systems and started to delve into microscopic systems. Ideas such as steroid loaded poly (lactic-co-glycolic acid), PLGA, microparticles came into existence. The next major jump came in the 1980s in the form of nanotherapeutics. There were some major technological advances that allowed this next generation of drug delivery systems to come along. Those ideas were PEGylation, active targeting, and the enhanced permeation and retention effect (EPR).
Some of the issues that had been seen with earlier renditions of nanoparticle drug delivery was that there were off target effects from drug being delivered to normal tissue, the delivery system wasnt highly controllable, and there wasnt optimal accumulation of drug in the targeted area. This is when the development of "smart drug delivery" originated. Encapsulated within the idea of smart drug delivery is the use of gated delivery systems. Researchers discovered that certain materials could be loaded and capped to prevent premature drug release. The caps could subsequently be removed using different external stimuli. This created a class of drug delivery systems that were able to solve a number of problems exhibited by normal nanoparticle drug delivery systems. These smart drug delivery systems are able to deliver the drug with minimal leakage, can be actively or passively targeted to different areas within the body, and will only release drug in the presence of certain triggers, creating a sustained local response and accumulation of drug at the disease area.