Synthesis of Novel Plant-Derived Encapsulated Radiolabeled Compounds for the Diagnosis of Parkinson's Disease and the Evaluation of Biological Effects with In Vitro/In Vivo Methods

Abstract

Abstract Parkinson's disease (PD) is a prevalent neurodegenerative disorder with a substantial impact on a significant number of individuals worldwide. Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in specific brain regions, namely the Substantia Nigra pars compacta (SNc) and striatum. The diagnosis of PD is utilized neuroimaging techniques, such as Single-photon emission computed tomography (SPECT), Positron emission tomography (PET), and Magnetic resonance imaging (MRI), which aid in the identification and evaluation of pathological changes associated with the disease. In this study, the focus was on developing technetium-99m ([99mTc]Tc) radiolabeled drug delivery systems using plant-derived compounds for the diagnosis of PD. Madecassoside (MA), a plant-derived compound, was conjugated with Levodopa (L-DOPA) to form MA-L-DOPA, which was then encapsulated using PLGA to create MA-PLGA and MA-L-DOPA-PLGA nanocapsules. Extensive structural analysis was performed using various methods such as Fourier Transform Infrared Spectroscopy (FTIR), Nuclear magnetic resonance spectroscopy (NMR), Liquid chromatography-mass spectrometry (LC-MS), thin layer chromatography (TLC), High-performance liquid chromatography (HPLC), Dynamic light scattering (DLS), and Scanning Electron Microscopy (SEM) to characterize the synthesized products. Radiochemical yields of 99mTc]Tc-MA, [99mTc]Tc-L-DOPA, [99mTc]Tc-MA-L-DOPA, [99mTc]Tc-MA-PLGA and [99mTc]Tc-MA-L-DOPA-PLGA were determined using thin layer radiochromatography (TLRC) and High-performance liquid radiochromatography (HPLRC) methods. In vitro cell culture studies were conducted on Human neuroblastoma (SY-SH5Y) and rat pheochromocytoma (PC-12) cell lines to assess the incorporation of radiolabeled compounds and the cytotoxicity of inactive compounds. Additionally, biodistribution studies were carried out on healthy male Sprague-Dawley rats and a Parkinson's disease experimental model to evaluate the compounds' bioactivity using [99mTc]Tc radiolabeled compounds. Overall, the results indicate that radiolabeled plant-derived encapsulated drug delivery systems with [99mTc]Tc hold potential as diagnostic agents for PD symptoms. This study contributes to the advancement of drug delivery agents in the field of brain research.