The aim of this overview is to review the evolution of the studies carried out, during more than 25 years,
on nanohydrogels obtained by self-assembling of pullulan (PUL) using several hydrophobization strategies.
After the first publications, mainly devoted to the preparation and characterization of PUL
nanogels, a remarkable number of studies demonstrated how wide can be the field of applications within
the main topic of biopharmaceutics. Numerous hydrophilic and lipophilic drugs were entrapped in the
nanogel networks, consequently PUL nanogels have been proposed as delivery systems for single drugs
and for combination therapies which allowed improvements of pharmacological activities and patient
compliance. Furthermore, the large amount of water content allowed loading also proteins which could
maintain their native structure and properties. Stimuli-sensitive and stealth PUL nanogel formulations
allowed improving the performances of antitumor drugs. These nanohydrogels have also been studied
for imaging techniques and for vaccines to be administered by injection and by mucosal application. The
studies on PUL nanogels are still in progress and the perspectives for future researches are also
addressed