Efficient encapsulation and sustained release of small hydrophilic molecules from traditional hydrogels have been challenging due to the large pore sizes of three dimensional networks and high water content. Furthermore, the encapsulated molecules are intended to be released from the hydrogel prior to use, resulting in a short shelf life of the formulation. On the other hand, hydrogels have been widely used in biomedical engineering applications due to their excellent biocompatibility, controllable biodegradability, tunable mechanical strength and porous structure, and ability to localize in desired locations compared with other types of biomaterials. Given these advantages, if hydrogels can effectively encapsulate small hydrophilic molecules and achieve sustained release, such hydrogels will have broad clinical implications in disease treatment. This research aims to develop a hydrogel that can obtain encapsulation and sustained release of small hydrophilic molecules.
We present hydration-induced injectable void-containing hydrogels based on hyperbranched polyglycerol-poly(propylene oxide)-hyperbranched polyglycerol (HPG-PPG-HPG) as an efficient delivery system for small hydrophilic molecules. Simply add HPG-PPG-HPG to an aqueous solution of a hydrophilic drug (tetrodotoxin (TTX)) and leave the mixture at 4°C overnight, HPG-PPG-HPG hydrated and formed a hydrogel and encapsulated TTX in hydrogel. We characterized the rheology properties of the hydrogels, measured the in vitro TTX release kinetics from the hydrogels, and evaluated the safety and pain relief efficacy of the hydrogel/TTX formulation in a rat sciatic nerve model.
The HPG-PPG-HPG hydrogel contains micron-sized voids, providing spaces to encapsulate hydrophilic drug inside (100% drug encapsulation efficiency). The voids are surrounded by a densely packed polymer matrix, which restricts drug transport to achieve sustained drug release over 24 hours in vitro. Hydrogels are injectable due to shear thinning properties. Furthermore, hydrogel/drug formulations can be stored in syringes for months with unchanged properties. In rats, HPG-PPG-HPG hydrogels increased the tolerated dose of TTX to 8 µg without any TTX-related systemic toxicity. A single injection of the HPG-PPG-HPG/TTX formulation produced sciatic nerve block lasting for 7 hours with minimal local toxicity.
