Polyamidoamine dendrimer-polyethylene glycol hydrogel for solubility enhancement and sustained release of diflunisal

The purpose of this research is to develop a hydrogel delivery system for solubility enhancement and sustained release of hydrophobic drugs. The model drug, diflunisal, has documented poor solubility in water which limits its application and administration. In this research, polyamidoamine (PAMAM) dendrimer is employed to dramatically increase the water solubility of diflunisal. In the meantime, PAMAM dendrimer functionalized with crosslinkers is further in situ crosslinked with thiolated polyethylene glycol (PEG) to form a hydrogel, encapsulating a high payload of diflunisal for sustained release. The diflunisal encapsulated hydrogel is immersed in water or laid on top of mouse skin, and the amount of diflunisal released from the gel is quantitatively measured by UV-Vis spectroscopy. Results show that the solubility of diflunisal in water is improved by 129–193 folds in the presence of PAMAM dendrimer at the experimental conditions compared to the reported solubility, and the amount of diflunisal is released by up to 87% of its load and reaches its maximum amounts after 72 h. This research demonstrates that the PAMAM dendrimer-PEG hydrogel system may serve as a promising delivery system for hydrophobic drugs.