Spray drying-assisted construction of hierarchically porous ZIF-8 for controlled release of doxorubicin.

The intrinsic properties and structure of carrier materials, as well as the drug-loading method, are crucial to the fabrication of high-performance controlled drug release systems. Metal-organic frameworks (MOFs) have attracted great attention in drug delivery due to their rich variety and very precisely designable structures, but their inherent small pores limit their application towards large-size drug molecules. Herein, we report a facile and efficient approach for the construction of hierarchically porous ZIF-8 (HP-ZIF-8) by spray drying. The homogeneously distributed mesopores, which result from the interspaces in the closely arranged nanosized ZIF-8 (N-ZIF-8), can be tuned by adjusting the primary particle size. More importantly, a drug (doxorubicin (DOX), for example) can be simultaneously encapsulated during the fabrication process of HP-ZIF-8, achieving a high loading rate of 79% and an encapsulation efficiency of 79%. Furthermore, we demonstrate that the obtained DOX@HP-ZIF-8 is a pH-responsive system and the release can also be controlled by the mesopore size. Although HP-ZIF-8 shows obvious advantages in drug loading and release performance compared with N-ZIF-8 loaded with DOX by the same solvent adsorption approach, DOX@HP-ZIF-8 displays significantly increased loading capacity (more than 3 times) and the slowest release rate due to its drug-loading method. Their therapeutic efficacy on HeLa cells has also been proved. These findings have important implications for the construction of HP-MOFs as drug carriers and will also present a new platform for controlled drug release and biomedical applications.