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.