Bimetallic zeolitic imidazolate framework as an active excipient of curcumin under physiological condition

Metal-organic frameworks (MOFs) hold great promises in biotechnological application. MOFs have been shown as efficient carriers of therapeutic drugs. Yet MOFs have not been used for simultaneous drug delivery and efficacy enhancement. In this study, a mixed metal MOF copper (Cu2+)-doped zeolitic imidazolate framework-8 (Cu/ZIF-8) was applied for the first time for simultaneous increment of drug stability (through metalation with zinc (Zn2+)) and functionality (via complexation with Cu2+). Copper was introduced in the tetrahedral sites of ZIF-8 in reactions conducted with 25% and 10% Cu2+ by weight of Zn2+ and the reaction time, temperature and metal to ligand ratios were optimized to ensure minimum distortions of ZIF-8 crystallinity. Further experiments were conducted with ZIF-8 prepared by 25% of Cu2+. The as synthesized (Cu Zn (2-methyl imidazolate)(2)) crystals were loaded with curcumin following a facile route at room temperature. Spectroscopic study of Cur@Cu/ZIF-8 revealed the nature of interaction to be metal chelation with or without adsorption while picosecond-resolved spectroscopic measurement depicted greater charge separation in Cur@Cu/ZIF-8 than Cu/ZIF-8. Cu/ZIF-8 exhibits reasonably high drug loading capacity (22%) with exceptionally high efficiency (83%). Attachment with Cu/ZIF-8 increased the aqueous stability of curcumin by several orders of magnitude. Reactive oxygen species (ROS) generation was amplified due to combined interactions of Zn2+ and Cu2+ representing d(10) and d(9) electronic configurations respectively and enhanced bond breaking tendency of peripheral-O-Hbond of curcumin molecule. Note worthily, Cur@Cu/ZIF-8 also exhibits greater anti-bacterial and anti-biofilm effects than free curcumin, a combination that is best suited for biomedical application.