Digital Intervention For The Management Of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive, multifactorial, chronic, neurodegenerative disease with high prevalence and limited therapeutic options, making it a global health crisis. Being the most common cause of dementia, AD erodes the cognitive, functional, and social abilities of the individual and causes escalating medical and psychosocial needs. As yet, this disorder has no cure and current treatment options are palliative in nature. There is an urgent need for novel therapy to address this pressing challenge. Digital therapeutics (Dtx) is one such novel therapy that is gaining popularity globally. Dtx provides evidence based therapeutic interventions driven by internet and software, employing tools such as mobile devices, computers, videogames, apps, sensors, virtual reality aiding in the prevention, management, and treatment of ailments like neurological abnormalities and chronic diseases. Dtx acts as a supportive tool for the optimization of patient care, individualized treatment and improved health outcomes. Dtx uses visual, sound and other non-invasive approaches for instance-consistent therapy, reminiscence therapy, computerised cognitive training, semantic and phonological assistance devices, wearables and computer-assisted rehabilitation environment to find applications in Alzheimer's disease for improving memory, cognition, functional abilities and managing motor symptom. A few of the Dtx-based tools employed in AD include "Memory Matters", "AlzSense", "Alzheimer Assistant", "smart robotic dog", "Immersive virtual reality (iVR)" and the most current gamma stimulation. The purpose of this review is to summarize the current trends in digital health in AD and explore the benefits, challenges, and impediments of using Dtx as an adjunctive therapy for the management of AD.

Design and Development of Novel Transdermal Nanoemulgel for Alzheimer's Disease: Pharmacokinetic, Pharmacodynamic and Biochemical Investigations.

BACKGROUND: Alzheimer's disease is a chronic progressive neurodegenerative disorder associated with depletion of acetylcholine. Oral treatment with tacrine hydrochloride; a reversible inhibitor of acetylcholinesterase, finds limited use in Alzheimer's disease due to frequent dosing, hepatotoxicity and extensive pre-systemic metabolism. OBJECTIVES: The objective of the study was to evaluate pharmacokinetic, pharmacodynamic, safety and stability profile of transdermal w/o nanoemulsion gel of tacrine hydrochloride and determine its relative bioavailability from transdermal nanogel in contrast to marketed capsule and conventional hydrogel. METHODS: The optimized nanoemulsion gel NEGT4 (droplet size 156.4 ±0.48 nm, with poly dispersity index 0.36 ±0.4, permeation flux 6.172±2.94 µg/cm2/h across rat skin) was prepared by spontaneous emulsification followed by sonication. NEGT4 contained 7 mg of drug in 10% w/w distilled water, 30% w/w surfactant (Labrafil M) and cosurfactant (Transcutol P) mixture in ratio 1:4 and 60 % Capryol 90 as oily phase thickened with 98.9 mg ethyl cellulose (20 cps). In vivo studies were carried out on male Wistar rats following standard guidelines. Scopolamine was used to induce amnesia in rats which is a characteristic of Alzheimer's disease. Various formulations were compared by performing pharmacokinetic, histopathological, behavioural and biochemical studies on rats. Stability studies on nanoemulsion gels were carried out in accordance with The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. RESULTS: Pharmacokinetic studies exhibited significantly greater extent of absorption from NEGT4 in comparison to capsule and hydrogel with a 2.18 and 5.26-fold increase respectively. Significant improvement in neurobehavioral parameters was observed with NEGT4 in scopolamine-induced amnesic rats. Biochemical assessment showed superior anti-amnesic activity of NEGT4 through augmentation of antioxidant enzymes, decreased lipid peroxidation and acetylcholinesterase activity. Low value of serum aminotransferase in rats treated with NEGT4 indicated the absence of hepatotoxicity. NEGT4 was found to be non-irritant and possessed a shelf life of 4.11 years. CONCLUSION: Developed nanoemulsion gel of tacrine hydrochloride was found to be safe, stable, and efficacious and has immense potential to be used in the therapy of Alzheimer's disease.

Appraisal of Transdermal Water-in-Oil Nanoemulgel of Selegiline HCl for the Effective Management of Parkinson's Disease: Pharmacodynamic, Pharmacokinetic, and Biochemical Investigations.

In the present study, the potential of transdermal nanoemulsion gel of selegiline hydrochloride for the treatment of Parkinson's disease was investigated. Water-in-oil nanoemulsions were developed by comparing low- and high-energy methods and were subjected to thermodynamic stability tests, in vitro permeation, and characterization studies. In vitro studies indicated that components of nanoemulsion acted as permeation enhancers with highest flux of 3.531 ± 1.94 µg/cm2/h from nanoemulsion SB6 containing 0.5 mg selegiline hydrochloride, 3% distilled water, 21% S mix (Span 85, Tween 80, PEG 400), and 76% isopropyl myristate by weight. SB6 with the least droplet size of 183.4 ± 0.35 nm, polydispersity index of 0.42 ± 0.06 with pH of 5.9 ± 0.32 and viscosity of 22.42 ± 0.14 cps was converted to nanoemulsion gel NEGS4 (viscosity = 22,200 ± 400 cps) by addition of Viscup160® for ease of application and evaluated for permeation, safety, and pharmacokinetic profile in Wistar rats. It provided enhancement ratio 3.69 times greater than conventional gel. NEGS4 showed 6.56 and 5.53 times increase in bioavailability in comparison to tablet and conventional gel, respectively, along with sustained effect. Therefore, the developed water-in-oil nanoemulsion gel promises to be an effective vehicle for transdermal delivery of selegiline hydrochloride.