Polyvinylpyrrolidone-Capped Copper Oxide Nanoparticles-Anchored Pramipexole Attenuates the Rotenone-Induced Phenotypes in a Drosophila Parkinson’s Disease Model

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.

On the additive artificial intelligence-based discovery of nanoparticle neurodegenerative disease drug delivery systems

“…On the one hand, we obtained the IFPTML-LDA by calculating the PTOs ΔD k (c j ) as the difference between the average value ⟨D k (c j )⟩ and the partition c n within of their own set. As result, the best IFPTML-LDA model found is as follows (Equation 5): (5) On the other hand, we tested the possibility to improve the results of statistical parameters for the IFPTML-LDA algorithm. To this end, we calculated the PTOs ΔD k (c j ) by performing all possible combinations among the average values ⟨D k (c j )⟩ of both vectors D nk and D dk with each partition.…”

“…These diseases encompass a diverse range of conditions characterized by the gradual deterioration of bodily structures and functions [ 2 – 3 ]. Although the exact causes leading to these diseases remain unidentified, there is evidence that oxidative damage plays a crucial role in the progressive neuronal cell death, particularly through the generation of reactive oxygen and nitrogen species [ 4 – 5 ]. In this regard, Alzheimer’s and Parkinson’s diseases are the most severe and untreatable conditions.…”

“…For simplicity, we are going to call them nanoparticle neuronal diseases drug delivery systems (N2D3Ss). N2D3Ss have the ability to protect NDDs from chemical and enzymatic degradation, direct the active compound towards the target site with a substantial reduction of toxicity for the adjacent tissues, and help the NDDs to pass physiological barriers, increasing bioavailability without resorting to high dosages [5,11]. Therefore, researchers are studying and developing new treatment approaches that use N2D3Ss for diagnosis and treatment [12][13][14][15].…”