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BACKGROUND: Cardiac arrhythmia, is a medical condition that reduces the heart's efficiency in pumping blood, and can be fatal, requires long-term management with conventional drugs, despite their limited efficacy. Diltiazem hydrochloride, chosen as a model drug, has a short biological half-life and extensive metabolism. Administering drug through skin is challenging, particularly due to the penetration via stratum corneum. However, solid lipid nanoparticles as a particulate carrier system can enhance its permeation and bioavailability. OBJECTIVE: The study aimed to develop a matrix type transdermal patch with diltiazem hydrochloride encapsulated in solid lipid nanoparticles Methods: The study used the solvent diffusion technique to prepare SLNs by mixing the drug and solid lipid in an organic phase at 80°C, then slowly adding it to an aqueous phase with continuous stirring for 45 minutes. The resulting nanodispersion was freeze-dried and analyzed for morphological studies, encapsulation efficiency & drug content. A patch was formulated using solvent evaporation technique, incorporating HPMC E50 (2% w/v), propylene glycol, and ethanolic oleic acid (1.5% v/v). SLNs loaded with diltiazem hydrochloride taken equivalent to diltiazem hydrochloride dose in the transdermal patch. The patch was then evaluated for In vitro and skin permeation studies. RESULTS: The result showed a positive correlation between lipid concentration and particle size. Probe sonication and homogenization increased particle size, while stirring speed reduced it. SEM and TEM images confirmed spherical particles with a size of 488.1±4.01nm and an entrapment efficiency of 55.03±1.99%. Drug release studies demonstrated 70.7% drug release from lipid matrix over 24 hrs. The formulated patch with uniform SLN distribution, had a drug content 89.37 ± 0.04% with a surface pH of 6.1 ± 0.53, close to skin pH. The uniformity of content in 3x3 patch estimated to be 14.587 ± 1.404 mg, close to the theoretical content 16.318 ± 1.08 mg, confirmed homogenous distribution of diltiazem hydrochloride SLNs throughout the patch diameter. Cumulative amount released from patch formulation at pH 5.6 and pH 7.4 was 518.1414µg/cm2 and 404.4466 µg/cm2. Synergistic flux enhancement was observed with oleic acid propylene glycol blend. Ex vivo study of the patch showed steady-state flux of 6.9 µg/cm2/hr, permeability coefficient 0.00362 cm/hr, diffusion coefficient 0.000103 cm/hr, cumulative drug permeation (Dmax) 814.885 µg after 24 hrs, and followed a Higuchi-matrix release model. CONCLUSION: The developed patch possessed improved bioavailability with reduced dosing and enhanced patient compliance.
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INTRODUCTION: The retina and brain exhibit similar pathologies in patients diagnosed with neurodegenerative diseases. The ability to access the retina through imaging techniques opens the possibility for non-invasive evaluation of Alzheimer's disease (AD) pathology. While retinal amyloid deposits are detected in individuals clinically diagnosed with AD, studies including preclinical individuals are lacking, limiting assessment of the feasibility of retinal imaging as a biomarker for early-stage AD risk detection. METHODS: In this small cross-sectional study we compare retinal and cerebral amyloid in clinically normal individuals who screened positive for high amyloid levels through positron emission tomography (PET) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial as well as a companion cohort of individuals who exhibited low levels of amyloid PET in the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study. We quantified the number of curcumin-positive fluorescent retinal spots from a small subset of participants from both studies to determine retinal amyloid deposition at baseline. RESULTS: The four participants from the A4 trial showed a greater number of retinal spots compared to the four participants from the LEARN study. We observed a positive correlation between retinal spots and brain amyloid, as measured by the standardized uptake value ratio (SUVr). DISCUSSION: The results of this small pilot study support the use of retinal fundus imaging for detecting amyloid deposition that is correlated with brain amyloid PET SUVr. A larger sample size will be necessary to fully ascertain the relationship between amyloid PET and retinal amyloid both cross-sectionally and longitudinally.
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The current study aimed to establish the mechanisms of antidiabetic activity of methanolic extract of Punica granatum leaves (MEPGL) in nicotinamide/streptozotocin-induced type 2 diabetes in rats. Phytochemical screening, HPLC analysis, and acute toxicity study of MEPGL were carried out. Various concentrations of MEPGL (100, 200, 400, and 600 mg/kg) were administered orally to diabetic rats for 45 days on a daily basis. The antidiabetic effect of MEPGL was examined by measuring blood glucose, plasma insulin, and glycated hemoglobin (HbA1c) levels, as well as with an oral glucose tolerance test. The antioxidant effect of MEPGL was determined by analyzing hepatic and renal antioxidant markers, namely superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and lipid peroxidation. The other biochemical markers alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), urea, and creatinine, as well as total cholesterol, triglycerides, and high-density lipoprotein (HDL) were also studied. Type 2 diabetes significantly altered these parameters, while oral administration of the MEPGL significantly ameliorated them. Moreover, the pancreatic histopathological changes were attenuated with MEPGL treatment. In a nutshell, oral MEPGL administration in diabetic rats showed antidiabetic activity due to its antioxidant activity, most probably due to the gallic acid, ellagic acid, and apigenin found in MEPGL.