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.

本研究的目的是开发一种水凝胶递送系统，用于提高疏水性药物的溶解度和缓释。模型药物二氟尼柳在水中的溶解度差，这限制了它的应用和给药。在这项研究中，聚酰胺胺 (PAMAM) 树枝状大分子用于显着提高二氟尼柳的水溶性。同时，用交联剂功能化的 PAMAM 树枝状大分子进一步与硫醇化聚乙二醇 (PEG) 原位交联，形成水凝胶，封装高有效载荷的二氟尼柳以实现缓释。将二氟尼柳包封的水凝胶浸入水中或铺在小鼠皮肤上，通过紫外-可见光谱定量测量从凝胶中释放的二氟尼柳量。结果表明，与报道的溶解度相比，在实验条件下，在 PAMAM 树枝状大分子存在下，二氟尼柳在水中的溶解度提高了 129-193 倍，并且二氟尼柳的释放量高达其负载量的 87%，并达到其72 小时后的最大量。该研究表明，PAMAM 树枝状大分子-PEG 水凝胶系统可作为一种有前途的疏水性药物递送系统。