Rational design of nanogels for overcoming the biological barriers in various administration routes

: Nanogels have been identified as outstanding nanocarrier candidates for drug delivery due to the desirable physiochemical properties and versatile applicability for diverse therapeutic molecules and imaging probes. One of the main challenges that hinder the clinical translation of nanogels is the low efficiency of drug transmitting to the target sites because of the impedance of complex biological barriers during the in vivo journey. The purpose of this review is to summarize the recent advances on the rational design and structure modulation of nanogels to overcome the barriers and challenges on the way to the site of action following various dosing modes. In particular, the functional moieties or domains were incorporated in the nanogels, allowing them to spontaneously regulate their structure and physiochemical properties to cross one or some of the multifaceted barriers. Importantly, the perspectives are presented in case of opportunities and challenges for the precise and efficacious therapeutic of nanogel formulations.