Background: Metal-organic frameworks (MOFs), composed of metal ions or clusters and organic ligands, have emerged as a new class of porous materials. However, the water instability of many MOFs impeded their further applications.

Objective: This study aimed to develop a facile method to incorporate γ-cyclodextrin based MOFs (CD-MOFs) into hydrophobic ethylcellulose (EC), and the obtained composite microparticles was expected to enhance their hydrolytic stability.

Materials and Methods: CD-MOFs@EC composite microparticles were prepared by the novel ultrafine particle processing system, which was invented by our group for effective MOFs-coating. CD-MOFs and CD-MOFs@EC composite microparticles were placed into a dryer at 25 °C and 90% ± 5% relative humidity (RH) for one month. The morphology and crystal structure of the samples at predetermined time points were characterized. Furthermore, the model drug, ketoprofen, was loaded into the composite microparticles, and the drug release profiles of the composite microparticles were investrigated.

Results: The composite microparticles appeared as spherical-like shape with sags because of the different solidification rates between the inside and the surface of the micro-droplets during the preparation process. The composite microparticles have well retained their morphology and crystal structure when exposed to an extreme humid environment, whereas the CD-MOFs underwent serious corrosion and aggregation with damaged crystal structure. The composite microparticles exhibited sustained and tunable pH dependent drug release profiles in simulated physiological condition, which demonstrated the composite microparticles might be promising as drug carries.

Conclusion: Based on these results, this study opens up a new avenue for stabilizing water-sensitive MOFs.