ABSTRACT
Parkinson's disease (PD) is a progressive, age-related neurodegenerative disease. The disease is characterized by the loss of dopaminergic neurons in the substantia nigra, pars compacta of the midbrain. Pramipexole (PPX) is a novel drug used for the treatment of PD. It has a high affinity for the dopamine (DA) D2 receptor subfamily and acts as a targeted mitochondrial antioxidant. It is less effective in the treatment of PD due to its short half-life, highly inconvenient dosing schedule, and long-term side effects. In recent years, PPX-loaded nanoformulations have been actively reported to overcome these limitations. In the current study, we focused on increasing the effectiveness of PPX by minimizing the dosing frequency and improving the treatment strategy for PD. Herein, we report the synthesis of biodegradable polyvinylpyrrolidone (PVP)-capped copper oxide nanoparticles (PVP-CuO NPs), followed by PPX anchoring on the surface of the PVP-CuO NPs (PPX-PVP-CuO NC), in a simple and inexpensive method. The newly formulated PPX-PVP-CuO NC complex was analyzed for its chemical and physical properties. The PPX-PVP-CuO NC was tested to protect against rotenone (RT)-induced toxicity in the Drosophila PD model. The in vivo studies using the RT-induced Drosophila PD model showed significant changes in negative geotaxis behavior and the level of DA and acetylcholinesterase. In addition, oxidative stress markers such as glutathione-S-transferase, total glutathione, thiobarbituric acid reactive species, and protein carbonyl content showed significant amelioration. The positive changes of PPX-PVP-CuO NC treatment in behavior, neurotransmitter level, and antioxidant level suggest its potential role in mitigating the PD phenotype. The formulation can be used for treatment or pharmacological intervention against PD.
ABSTRACT
Brain glioma is the most lethal type of cancer, with extremely poor prognosis and high relapse. Unfortunately, the treatment of brain glioma is often limited because of the low permeability of anticancer drugs across the blood-brain barrier (BBB). To circumvent this, magnetic mesoporous nanoparticles were synthesized and loaded with doxorubicin as an anticancer agent. These nanoparticles were fabricated with Pluronic F-127 and subsequently conjugated with transferrin (Tf) to achieve the sustained release of the drug at the targeted site. The physicochemical properties of the conjugated nanoparticles were analyzed using different techniques. The magnetic saturation of the nanoparticles determined by a vibration sample magnetometer was found to be 26.10 emu/g. The cytotoxicity study was performed using the MTT assay at 48 and 96 h against the U87 cell line. The Tf-conjugated nanoparticles (DOX-MNP-MSN-PF-127-Tf) exhibited a significant IC50 value (0.570 µg/mL) as compared to the blank nanoparticles (121.98 µg/mL). To understand the transport mechanism of drugs across the BBB, an in vitro BBB model using human brain microvascular endothelial cells was developed. Among the nanoparticles, the Tf-conjugated nanoparticles demonstrated an excellent permeability across the BBB. This effect was predominant in the presence of an external magnetic field, suggesting that magnetic particles present in the matrix facilitated the uptake of drugs in U87 cells. Finally, it is concluded that nanoparticles conjugated with Tf effectively crossed the BBB. Thus, the developed nanocarriers can be considered as potential candidates to treat brain tumor.
