New and Enzymatic Targeted Magnetic Macromolecular Nanodrug System Which Delivers Methadone and Rifampin Simultaneously.

An indicator for cytochrome P450 (CYP-450) enzymes includes CYP-450 which has the most fundamental role in methadone metabolism in the liver. The aim of this study is to design and interface a macromolecular nanodrug system to deliver rifampin (RIF) and methadone (MTD) simultaneously to the liver based on magnetic nanoparticles (MNPs). RIF increases the metabolism of MTD in the liver. In this study, MTD was linked to a magnetic nanocapsule including RIF by a heterocyclic linker. This heterocyclic linker was prepared in five steps. Fourier transform infrared spectroscopy and NMR indicated the synthesis of the heterocyclic linker, scanning electron microscopy and confocal fluorescence microscopy exhibited the morphology of NPs and loading MTD. Atomic force microscopy was applied to indicate the three-dimensional topology of NPs and the conglomeration on them. Magnetization properties of loaded and unloaded NPs were characterized by vibrating-sample magnetometer. These patterns indicated superparamagnetic properties of MNPs therefore these NPs do not retain any magnetism after removal of a magnetic field. In vitro release studies of RIF and MTD by UV-vis measurements in several buffer solutions demonstrated that behavior of drug release is related to pH. The histopathology study was performed on the liver of rats injected with MTD, morphine (MOR), and the prepared drug. Cytotoxicity of the prepared sample on MCF-7 cell line assay was assessed via 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide solution. The histopathology study indicated that the cotreatment of the synthesized drug attenuated hepatic lesions. Delivery of RIF and MTD simultaneously to the liver by MNPs (1) increases MTD metabolism because of increasing CYP-450 enzymes induced by RIF and (2) decreases hepatic lesions via injection of the synthesized drug with cotreatment by MOR.