Sustained-release drugs refer to the formulations that release drugs continuously at a predetermined rate. With the growth of medical demand, new formulations of sustained release have developed one after another. However, there are still problems such as ineffective sustained release, easy volatilization of dispersed phase, low reproducibility and low encapsulation rate. There is an increasing need to develop a new sustained-release formulation method with good biocompatibility, controllable sustained release and multiple drug universality. 

This work shows a controllable formulation method of nano-composite hydrogels for drug co-delivery and sustained release. Our formulation achieves more than 90% drug release, and the total release time could be tuned from 4h to 72h. The structure of the drug-loaded hydrogel is constructed from the nanoscale to the microscale. Nanoparticles are used as versatile carriers in drug delivery, and their small size and modifiable physicochemical properties support the design of targeting capabilities, therapeutic cargo and surface functionalization. We fabricated anti-inflammatory drug and local anesthetics nanoparticles with the uniform size distribution. Compared with organic drug molecules, they present unique advantages, including high loading capacity, good water solubility, co-delivery, extended stability and crosslink ability. To further enhance therapeutic efficacy and sustained release, we combine drug-loaded nanoparticles with biocompatible hydrogels by chemical bonds to formulate delivery systems. The PEGDA bio-scaffold ensures that the nano-sized drug particles remain at the target site and also function as a controlled-release reservoir for the therapeutic drug for a prolonged period. The mechanical properties and shape of the scaffold can be designed to match different application scenarios.