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Mustafa K Shehata,1 Assem A Ismail,1 Maher A Kamel2 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, EgyptCorrespondence: Mustafa K Shehata, Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Khartoum Square, Azzarita, Alexandria, 21521, Egypt, Tel +20 1114740302, Fax +002/23/4871668, Email mostfak290@gmail.com; mostafa.shokdef@alexu.edu.egIntroduction: Donepezil (DPL), a specific acetylcholinesterase inhibitor, is used as a first-line treatment to improve cognitive deficits in Alzheimer’s disease (AD) and it might have a disease modifying effect. Astaxanthin (AST) is a natural potent antioxidant with neuroprotective, anti-amyloidogenic, anti-apoptotic, and anti-inflammatory effects. This study aimed to prepare nanostructured lipid carriers (NLCs) co-loaded with donepezil and astaxanthin (DPL/AST–NLCs) and evaluate their in vivo efficacy in an AD-like rat model 30 days after daily intranasal administration.Methods: DPL/AST–NLCs were prepared using a hot high-shear homogenization technique, in vitro examined for their physicochemical parameters and in vivo evaluated. AD induction in rats was performed by aluminum chloride. The cortex and hippocampus were isolated from the brain of rats for biochemical testing and histopathological examination.Results: DPL/AST–NLCs showed z-average diameter 149.9 ± 3.21 nm, polydispersity index 0.224 ± 0.017, zeta potential – 33.7 ± 4.71 mV, entrapment efficiency 81.25 ± 1.98% (donepezil) and 93.85 ± 1.75% (astaxanthin), in vitro sustained release of both donepezil and astaxanthin for 24 h, spherical morphology by transmission electron microscopy, and they were stable at 4– 8 ± 2°C for six months. Differential scanning calorimetry revealed that donepezil and astaxanthin were molecularly dispersed in the NLC matrix in an amorphous state. The DPL/AST–NLC-treate

[Aim]: To explore the antidiabetic effect of superparamagnetic iron oxide nanoparticles (SPIONs)-PEG-550 and its related metabolic pathways in muscles and kidney., [Materials & methods]: Diabetes was induced in 5-day neonatal rats; after confirming diabetes, treatment with SPIONs-PEG-550 started at different doses for 4 weeks. Routine analysis of glucose, insulin, adipocytokines, urea and creatinine was performed. The expression of several genes involved in metabolic pathways and the corresponding protein levels were examined., [Results & conclusion]: SPIONs-PEG-550 normalized the disturbed glucose homeostasis, reversed insulin resistance, adjusted the serum level of adipocytokines, and improved several disturbed downstream effectors of the insulin signaling and WNT pathway in both tissues. Histological examination of the muscle and pancreas has shown almost normal functional characteristics without remarkable adverse effects on the kidney.

Mustafa K Shehata,1 Assem A Ismail,1 Maher A Kamel2 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, EgyptCorrespondence: Mustafa K Shehata, Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Khartoum Square, Azzarita, Alexandria, 21521, Egypt, Tel +20 1114740302, Fax +20 3 4871668, Email mostfak290@gmail.com; mostafa.shokdef@alexu.edu.egBackground: Astaxanthin (AST) is a second-generation antioxidant with anti-inflammatory and neuroprotective properties and could be a promising candidate for Alzheimer’s disease (AD) therapy, but is shows poor oral bioavailability due to its high lipophilicity.Purpose: This study aimed to prepare and evaluate AST–loaded nanostructured lipid carriers (NLCs), for enhanced nose-to-brain drug delivery to improve its therapeutic efficacy in rat model of AD.Methods: AST–NLCs were prepared using hot high-pressure homogenization technique, and processing parameters such as total lipid-to-drug ratio, solid lipid-to-liquid lipid ratio, and concentration of surfactant were optimized.Results: The optimized AST–NLCs had a mean particle size of 142.8 ± 5.02 nm, polydispersity index of 0.247 ± 0.016, zeta potential of – 32.2 ± 7.88 mV, entrapment efficiency of 94.1 ± 2.46%, drug loading of 23.5 ± 1.48%, and spherical morphology as revealed by transmission electron microscopy. Differential scanning calorimetry showed that AST was molecularly dispersed in the NLC matrix in an amorphous state, whereas Fourier transform infrared spectroscopy indicated that there is no interaction between AST and lipids. AST displayed a biphasic release pattern from NLCs; an initial burst release followed by sustained release for 24 h. AST-NLCs were stable at 4– 8 ± 2°C for six months. Intranasal treatment of AD-like rats with the optimized AST–NLCs significantly decreased oxidative stress, am

[Background]: Obesity is a pandemic disease that is rapidly growing into a serious health problem and has economic impact on healthcare systems. This bleak image has elicited creative responses, and nanotechnology is a promising approach in obesity treatment. This study aimed to investigate the anti-obesity effect of superparamagnetic iron oxide nanoparticles (SPIONs) on a high-fat-diet rat model of obesity and compared their effect to a traditional anti-obesity drug (orlistat)., [Methods]: The obese rats were treated daily with orlistat and/or SPIONs once per week for 8 weeks. At the end of the experiment, blood samples were collected for biochemical assays. Then, the animals were sacrificed to obtain white adipose tissues (WAT) and brown adipose tissues (BAT) for assessment of the expression of thermogenic genes and mitochondrial DNA copy number (mtDNA-CN)., [Results]: For the first time, we reported promising ameliorating effects of SPIONs treatments against weight gain, hyperglycemia, adiponectin, leptin, and dyslipidemia in obese rats. At the molecular level, surprisingly, SPIONs treatments markedly corrected the disturbed expression and protein content of inflammatory markers and parameters controlling mitochondrial biogenesis and functions in BAT and WAT., [Conclusions]: SPIONs have a powerful anti-obesity effect by acting as an inducer of WAT browning and activator of BAT functions.