A zirconium-based metal-organic framework with encapsulated anionic drug for uncommonly controlled oral drug delivery

摘要

Oral drug delivery has been recognized as the most common and patient acceptant drug administration. In general, an ideal drug carrier for oral drug delivery should own high drug loading capacity, good biocompatibility, and especially the feature of avoiding drug delivery in stomach (acidic conditions) and promoting the drug release in intestine (neutral conditions). Generally, most of MOFs for drug carriers exhibit the normal pH response in which the drugs are more easily released in acidic condition because of the degradation of the framework or/and the weak host-guest interactions, so they are not suitable for oral drug delivery. Herein, we design and synthesize a new nitrogen heterocycle organic ligand H(2)QDDA ((2E,2'E)-3,3'-(quinoline-5,8-diyl) diacrylic acid) and use it to construct its first Zr-based MOF (termed as ZJU-802). The anionic drug encapsulated ZJU-802 exhibit an uncommonly reverse pH response due to the incorporation of N sites in which the anionic drugs can be easily released at pH 7.4 while have a negligible release at pH 2.0 due to the enhanced host-guest interactions between the framework and anionic drugs. This reversed drug release is quite suitable for oral drug delivery. Further, high anionic drug loading capacities ( 40%), low cytotoxicity and good biocompatibility of ZJU-802 were fully demonstrated by H-1 NMR, MIT assay and confocal microscopy imaging.