Huntington's Disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansion in the HTT gene, producing toxic mutant huntingtin (mHTT) protein. This leads to progressive motor dysfunction, cognitive decline, and psychiatric disturbances. Despite advances in understanding mHTT toxicity, potentially disease-modifying therapies remain scarce, underscoring the need for novel approaches targeting core pathophysiological mechanisms. Klotho, a multifunctional anti-aging protein, regulates several pathways relevant to neuronal survival and may have relevance to HD pathophysiology. Klotho is a co-receptor with a membrane and is a soluble co-receptor that regulates synaptic and metabolic homeostasis. Although direct experimental evidence in HD remains limited, emerging findings from aging and neurodegeneration research suggest that Klotho-mediated pathways may influence mechanisms relevant to HD pathogenesis. It suppresses fibroblast growth factor receptor (FGFR) signaling and major pathways such as PI3K/Akt-FOXO, Wnt/ -catenin and insulin/IGF-1 pathways, which oppose the hallmarks of HD, namely excitotoxicity, calcium dysregulation, impaired neuroprotection, and peripheral neuroinflammation. There is growing evidence of the involvement of Klotho in mitochondrial health and biogenesis, mitophagy coordination, and oxidative stress resistance - direct mitigating cellular toxicity caused by mHTT. These mechanistic overlaps suggest that Klotho signaling may represent a potential area for investigation in HD. It deals with oxidative stress, excitotoxicity, inflammation, and metabolic dysregulation, and compares it to other diseases of the neurodegenerative type in which Klotho deficits contribute to pathology. Such a structure encourages Klotho-based interventions as a new, mechanism-based approach to HD. Further experimental studies are required to determine whether modulation of Klotho signaling could influence disease progression in HD.
Nanoemulsions (NEs) are kinetically stable, thermodynamically unstable colloidal systems composed of nanoscale oil and aqueous domains stabilized primarily by surfactants and, where required, co-surfactants. Their small droplet size, large interfacial area, and tunable physicochemical properties provide opportunities to improve the solubilization, dispersion, permeation, stability, and bioavailability of poorly water-soluble and labile therapeutic agents. This review provides a comprehensive overview of the principles governing NE formulation and their evolving role in pharmaceutical and biomedical applications. Particular emphasis is placed on the selection and functional contribution of formulation components, high- and low-energy preparation approaches, scale-up and manufacturing considerations, critical quality attributes, physicochemical characterization, stability, and nano-bio interactions. The review further summarizes the application of NEs in oral, topical, ocular, pulmonary, parenteral, vaccine, immunological, and disease-specific drug delivery, together with emerging applications in theranostics and imaging. The available evidence indicates that NEs can enhance drug solubilization and delivery performance and can be engineered to incorporate therapeutic and imaging functionalities; however, the extent of targeting and clinical benefit remains dependent on formulation composition, biological barriers, disease heterogeneity, and the stage of translational development. Emerging artificial intelligence (AI) and machine-learning approaches show potential for formulation optimization, prediction of physicochemical and biological behaviour, and interpretation of complex imaging data, but their application to NE systems remains an evolving area constrained by data standardization, model transparency, reproducibility, and regulatory considerations. Major challenges to clinical translation include physical and chemical instability, limitations of passive and active targeting, manufacturing complexity, batch-to-batch reproducibility, scale-up, safety assessment, and regulatory requirements. Overall, NEs represent versatile platforms for pharmaceutical delivery and multifunctional biomedical applications, while further systematic validation, scalable manufacturing, standardized characterization, and clinically relevant evidence are required to translate promising laboratory findings into robust and clinically useful products.
Gastroesophageal reflux disease (GERD) is the most common disorder with a significantly high global prevalence. Prokinetic drugs are commonly recommended for the treatment of gastric reflux, in addition to antacids and antisecretory agents. Itopride hydrochloride, a prokinetic agent, acts as a D2 receptor antagonist and an acetylcholinesterase inhibitor, improving GERD symptoms. The objective of this study was to develop a floating-type gastroretentive drug delivery system, which was further evaluated by in vitro and in vivo studies. Itopride hydrochloride-loaded gastroretentive pellets were prepared using pelletization followed by spheronization. The preparation of itopride-loaded gastroretentive pellets was optimized using a central composite experimental design (32), varying the concentrations of ethylcellulose and Eudragit S100 as independent variables, while floating time and percentage of drug release were considered dependent variables.The optimized batch was characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FTIR). It was then evaluated for mucoadhesion, in vivo gastric retention, and bioavailability in rabbits. The in vitro drug release from the optimized pellet formulation exhibited approximately 97.84% release over 10 h and maintained buoyancy for up to 9 h. In vivo gastric residence time was observed to be 6 h, with a bioavailability of 52.87 ± 0.15 µg/mL/h. Based on in vitro and in vivo findings, the developed gastroretentive mucoadhesive pellet formulation presents a promising drug delivery system for the treatment of GERD, potentially enhancing drug efficacy through prolonged gastric retention.