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

Abstract

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.