Neuroprotective Role of Phytoconstituents-based Nanoemulsion for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder (ND), affecting more than 44 million individuals globally as of 2023. It is characterized by cognitive dysfunction and an inability to perform daily activities. The progression of AD is associated with the accumulation of amyloid beta (Aß), the formation of neurofibrillary tangles (NFT), increased oxidative stress, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum stress. Presently, various phytomedicines and their bioactive compounds have been identified for their neuroprotective effects in reducing oxidative stress, alleviating neuroinflammation, and mitigating the accumulation of Aß and acetylcholinesterase enzymes in the hippocampus and cerebral cortex regions of the brain. However, despite demonstrating promising anti-Alzheimer's effects, the clinical utilization of phytoconstituents remains limited in scope. The key factor contributing to this limitation is the challenges inherent in traditional drug delivery systems, which impede their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted drug solubility and stability, brief duration of action, and a lack of control over drug release. Consequently, these constraints result in diminished bioavailability and insufficient permeability across the blood-brain barrier (BBB). In response to these challenges, novel drug delivery systems (NDDS) founded on nanoformulations have emerged as a hopeful strategy to augment the bioavailability and BBB permeability of bioactive compounds with poor solubility. Among these systems, nanoemulsion (NE) have been extensively investigated for their potential in targeting AD. NE offers several advantages, such as ease of preparation, high drug loading, and high stability. Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced permeability of the drug in systemic circulation and the brain. Various studies have reported the testing of NE-based phytoconstituents and their bioactives in different animal species, including transgenic, Wistar, and Sprague-Dawley (SD) rats, as well as mice. However, transgenic mice are commonly employed in AD research to analyze the effects of Aß. In this review, various aspects such as the neuroprotective role of various phytoconstituents, the challenges associated with conventional drug delivery, and the need for NDDS, particularly NE, are discussed. Various studies involving phytoconstituent-based NE for the treatment of AD are also discussed.

Application of quality by design in optimization of nanoformulations: Principle, perspectives and practices.

Nanoparticulate drug delivery systems (NDDS) based nanoformulations have emerged as promising drug delivery systems. Various NDDS-based formulations have been reported such as polymeric nanoparticles (NPs), nanoliposomes, solid lipid NPs, nanocapsules, liposomes, self-nano emulsifying drug delivery systems, pro liposomes, nanospheres, microemulsion, nanoemulsion, gold NPs, silver NPs and nanostructured lipid carrier. They have shown numerous advantages such as enhanced bioavailability, aqueous solubility, permeability, controlled release profile, and blood-brain barrier (BBB) permeability. This advantage of NDDS can help to deliver pure drugs to the target site. However, the formulation of nanoparticles is a complex process that requires optimization to ensure product quality and efficacy. Quality by Design (QbD) is a systemic approach that has been implemented in the pharmaceutical industry to improve the quality and reliability of drug products. QbD involves the optimization of different parameters like zeta potential (ZP), particle size (PS), entrapment efficiency (EE), polydispersity index (PDI), and drug release using statistical experimental design. The present article discussed the detailed role of QbD in optimizing nanoformulations and their advantages, advancement, and applications from the industrial perspective. Various case studies of QbD in the optimization of nanoformulations are also discussed.

Opening avenues for treatment of neurodegenerative disease using post-biotics: Breakthroughs and bottlenecks in clinical translation.

Recent studies have indicated the significant involvement of the gut microbiome in both human physiology and pathology. Additionally, therapeutic interventions based on microbiome approaches have been employed to enhance overall health and address various diseases including aging and neurodegenerative disease (ND). Researchers have explored potential links between these areas, investigating the potential pathogenic or therapeutic effects of intestinal microbiota in diseases. This article provides a summary of established interactions between the gut microbiome and ND. Post-biotic is believed to mediate its neuroprotection by elevating the level of dopamine and reducing the level of α-synuclein in substantia nigra, protecting the loss of dopaminergic neurons, reducing the aggregation of NFT, reducing the deposition of amyloid ß peptide plagues and ameliorating motor deficits. Moreover, mediates its neuroprotective activity by inhibiting the inflammatory response (decreasing the expression of TNFα, iNOS expression, free radical formation, overexpression of HIF-1α), apoptosis (i.e. active caspase-3, TNF-α, maintains the level of Bax/Bcl-2 ratio) and promoting BDNF secretion. It is also reported to have good antioxidant activity. This review offers an overview of the latest findings from both preclinical and clinical trials concerning the use of post-biotics in ND.