Browsing by Author "Amer, Reham"

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    Efficient lung-targeted delivery of risedronate sodium/vitamin D3 conjugated PAMAM-G5 dendrimers for managing osteoporosis: Pharmacodynamics, molecular pathways and metabolomics considerations
    (Elsevier Inc., 2022-09) Elsayyad, Nihal Mohamed Elmahdy; Gomaa, Iman; Salem, Mohamed A; Amer, Reham; El-Laithy, Hanan M
    Aims: This study aims at formulating combined delivery of Risedronate sodium (RIS) and Vitamin D3 (VITD3) for augmented therapeutic outcome against osteoporosis (OP) using deep lung targeted PAMAM-G5-NH2 dendrimers to minimize RIS gastrointestinal side effects and enhance both drugs bioavailability through absorption from the alveoli directly to the blood. Methods: RIS-PAMAM-G5-NH2, VITD3-PAMAM-G5-NH2, and RIS/VITD3-PAMAM-G5-NH2 were prepared and evaluated in vitro for particle size (PS), zeta potential (ZP), %loading efficiency (%LE), morphology and FTIR. The efficacy of the RIS/VITD3-PAMAM-G5-NH2 compared to oral RIS was evaluated in OP-induced rats by comparing serum calcium, phosphorus, and computed bone mineral density (BMD) pre- and post-treatment. Additionally, a comprehensive metabolomics and molecular pathways approach was applied to find serum potential biomarkers for diagnosis and to evaluate the efficacy of inhaled RIS/VITD3-PAMAM-G5-NH2. Key findings: RIS/VITD3-PAMAM-G5-NH2 was successfully prepared with a %LE of 92.4±6.7% (RIS) and 83.2±4.4% (VIT-D3) and a PS of 252.8±34.1 adequate deep lung delivery. RIS/VITD3- PAMAM-G5-NH2 inhalation therapy was able to restore serum calcium, phosphorus, and BMD close to normal levels after 21 days of treatment in OP-induced rats. The WNT-signalling pathway and changes in the metabolite levels recovered to approximately normal levels upon treatment. Moreover, histone acetylation of the WNT-1 gene and miR-148a-3p interference proved to play a role in the regulation of the WNT-signalling pathway during OP progression and treatment. Significance: Pulmonary delivery of RIS/VITD3-PAMAM-G5-NH2 offers superior treatment for OP treatment compared to the oral route. Molecular and Metabolic pathways offer a key indicator of OP diagnosis and progression.
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    Ezetimibe-Loaded Nanostructured Lipid Carrier for Oral Delivery: Response Surface Methodology; In Vitro Characterization and Assessing the Antihyperlipidemic Effect in Rats
    (American Chemical Society, 2024-02) Elkhayat, Dalia; Abdelmalak, Nevine S; Amer, Reham; Awad, Heba H
    Among the independent risk factors for the occurrence of cardiovascular diseases like atherosclerosis is hyperlipidemia. To decrease cardiovascular events and patient mortality, antihyperlipidemia therapy is crucial. Our study aimed to enhance the solubility of the poorly soluble lipid-lowering agent ezetimibe (EZ), a member of class II as per the Biopharmaceutics Classification System (BCS). The drug was formulated as a nanostructured lipid carrier (NLC) employing the ultrasonication technique. A response surface D-optimal design was employed to study the effect of changing the liquid lipid type and the percentage of liquid lipid with respect to total lipid amount on the particle size, zeta potential, percentage entrapment efficiency, and percentage of drug released after 24 h. Nine NLC formulations were prepared and pharmaceutically evaluated, and the optimized NLC formulation was selected, further characterized, and evaluated as well. Optimized EZ-NLC was assessed in the high-fat diet model to induce hyperlipidemia in rats in comparison with the EZ suspension. The results of the optimized formulation showed that the prepared NLCs were spherical with no aggregation having a particle size of 204.3 ± 19.17 nm, zeta potential equal to −32 ± 7.59 mV, and entrapment efficiency of 81.5 ± 3.58% and 72.15 ± 4.58% drug released after 24 h. EZ-NLC significantly decreased the elevated serum lipid parameters, including total cholesterol, triglycerides, and LDL-C, but significantly normalized serum HDL-C levels of rats kept on a high-fat diet. The results demonstrated the improved efficacy of EZ-NLC in ameliorating the elevated serum lipid parameters compared to EZ.