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In 1989, Lupron Depot TM , a controlled-release formulation for prostate cancer, became one of the first commercial products to use PLGA microspheres 113,114

As the primary factors for the reduced anticancer effect 1) the reduced delivery and uptake of the anticancer agent, 2) the need for the conversion of molecular oxygen (O 2 ) into reactive oxygen species (ROS), 3) the preferred therapeutic effect against highly proliferating cells, which is reduced under hypoxic conditions, or 4) adaptation of the cancer cells by promoting cell survival and upregulating certain resistance pathways, has been suggested 1,2,3,4,5