Paper Title
Optimization and Cytotoxicity Studies of Dye-Loaded Zeolitic Imidazole Framework-8 (ZIF-8) for Drug Delivery Applications

Abstract
Zeolitic imidazolate frameworks-8 (ZIF-8) nanoparticles have been used as a drug carrier for drug delivery applications. However, the property of drugs play an important parameter in order to incorporate into the ZIF-8 nanoparticles.Herein,fluorescein sodium (Flu), toluidine blue O (TBO), and nilered (NiR), were used as mock drug compounds (water-soluble or -insoluble compounds)to be encapsulatedintoZIF-8.The ZIF-8 nanoparticles showed the encapsulation efficiency of Flu, TBO, and NiR at39.4%, 55.6%, and 37.5%, respectively. The highestencapsulation efficiency was caused by the strong interaction between the dyes (TBO and Flu) and the nanoparticles.The particles size of ZIF-8 anddye-loaded ZIF-8 were approximately165 and 110 nm.The zeta potentials of Flu, TBO, and NiR-loaded ZIF-8 were -15.57, -3.37, and -31.63 mV, respectively.A completed release of Flufrom Flu-loaded ZIF-8was recorded in an acidic condition within 1 hour due to the degradation of the ZIF-8 nanoparticles structure. However, TBO could not release from the carrier because of the strong interaction between the dye molecules and ZIF-8 nanoparticles.Due to the water-insoluble property of NiR, the release of NiRcould not be detected in an in vitro experiment. Moreover,L929 cell viability usingMTT assay was related to theresult from determination of the released LDH. The IC50values of those dyes-loaded ZIF-8 nanoparticles were approximately 21-26 µg/mlwhich were corresponding to the level of released LDH (~50%) at the same concentration range.Theseresults are providing the prospect and the potential of the use of ZIF-8 nanoparticles for future development byincorporating hydrophilic or hydrophobic compounds. Keywords - Cytotoxicity, Drug delivery system, Dyes, Nanoparticles, ZIF-8.