Crossing biological barriers with nanogels to improve drug delivery performance

The current limitations in the use of nanocarriers to treat constantly evolving diseases call for the design of novel and smarter drug delivery systems (DDS). Nanogels (NGs) are three-dimensional crosslinked polymers with dimensions on the nanoscale and with a great potential for use in the biomedical field. Particular interest focuses on their application as DDS to minimize severe toxic effects and increase the therapeutic index of drugs. They have recently gained attention, since they can include responsive modalities within their structure, which enable them to excerpt a therapeutic function on demand. Their bigger sizes and controlled architecture and functionality, when compared to non-crosslinked polymers, make them particularly interesting to explore novel modalities to cross biological barriers. The present review summarizes the most significant developments of NGs as smart carriers, with focus on smart modalities to cross biological barriers such as cellular membrane, tumor stroma, mucose, skin, and blood brain barrier. We discuss the properties of each barrier and highlight the importance that the NG design has on their capability to overcome them and deliver the cargo at the site of action.