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      Evaluation of Different Surface Coating Agents for Selenium Nanoparticles: Enhanced Anti-Inflammatory Activity and Drug Loading Capacity


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          Inflammation is the keystone in the disease’s pathological process in response to any damaging stimuli. Therefore, any agent that inhibits the inflammatory response is under focus, either a drug or a bioactive compound. Selenium nanoparticles have drawn attention in various biomedical applications, including the anti-inflammatory activity.


          In the current study, we aimed to evaluate the capacity of different surface coating materials (soybean lecithin, PEG 6000, and β-cyclodextrin) to enhance the anti-inflammatory activity of the synthesized selenium nanoparticles (SeNPs). The capability of the coated SeNPs to adsorb indomethacin (IND) on their surfaces compared to the uncoated SeNPs was also evaluated.


          SeNPs were synthesized, coated with different materials, and characterized in vitro using X-ray diffraction, UV-Vis spectrophotometer, FTIR, SEM, TEM, and particle size and zeta potential measurements. The in vivo anti-inflammatory activity of the uncoated/coated SeNPs loaded into hydrogel was evaluated using a carrageenan-induced paw edema rat model. The effect of SeNPs surface coatings was further evaluated for IND loading capacity.


          Our findings proved the superior anti-inflammatory activity of all coated SeNPs compared to the uncoated SeNPs, especially with β-cyclodextrin surface coating. Regarding the IND loading capacity of the prepared uncoated/coated SeNPs, the amount of drug loaded was 0.12, 1.12, 0.3, and 0.14 µg IND/µg SeNPs for the uncoated, lecithin-, PEG- and β-CD-coated SeNPs, respectively.


          Surface functionalization of SeNPs can provide a synergistic therapeutic activity. Our results are promising for further investigation of the in vivo anti-inflammatory synergistic activity of the IND-loaded surface-coated SeNPs.

          Graphical Abstract

          Most cited references73

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          Inflammation and atherosclerosis.

          Atherosclerosis, formerly considered a bland lipid storage disease, actually involves an ongoing inflammatory response. Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and, ultimately, the thrombotic complications of atherosclerosis. These new findings provide important links between risk factors and the mechanisms of atherogenesis. Clinical studies have shown that this emerging biology of inflammation in atherosclerosis applies directly to human patients. Elevation in markers of inflammation predicts outcomes of patients with acute coronary syndromes, independently of myocardial damage. In addition, low-grade chronic inflammation, as indicated by levels of the inflammatory marker C-reactive protein, prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors. Moreover, certain treatments that reduce coronary risk also limit inflammation. In the case of lipid lowering with statins, this anti-inflammatory effect does not appear to correlate with reduction in low-density lipoprotein levels. These new insights into inflammation in atherosclerosis not only increase our understanding of this disease, but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance.
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            Selenium in food and the human body: a review.

            Selenium levels in soil generally reflect its presence in food and the Se levels in human populations. Se food content is influenced by geographical location, seasonal changes, protein content and food processing. Periodic monitoring of Se levels in soil and food is necessary. Diet is the major Se source and approximately 80% of dietary Se is absorbed depending on the type of food consumed. Se bioavailability varies according to the Se source and nutritional status of the subject, being significantly higher for organic forms of Se. Se supplements can be beneficial for subjects living in regions with very low environmental levels of Se. Several strategies have been followed: (1) employment of Se-enriched fertilizers; (2) supplementation of farm animals with Se; (3) consumption of multimicronutrient supplements with Se. Nevertheless, detailed investigations of possible interactions between Se supplements and other food components and their influence on Se bioavailability are needed. Suppliers also need to provide more information on the specific type of Se used in supplements. In addition, research is lacking on the mechanisms through which Se is involved in hepatocyte damage during hepatopathies. Although Se potential as an antioxidant for the prevention of cardiovascular diseases (CVD) is promising, additional long-term intervention trials are necessary. As a result, indiscriminate Se supplements cannot be reliably recommended for the prevention of CVD in human beings. Some interesting findings reported an association of Se intake with a reduced prevalence and risk for prostate and colon cancer. However, random trials for other cancer types are inconclusive. As a final conclusion, the general population should be warned against the employment of Se supplements for prevention of hepatopathies, cardiovascular or cancer diseases, because benefits of Se supplementation are still uncertain, and their indiscriminate use could generate an increased risk of Se toxicity.
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              Selective cellular uptake and induction of apoptosis of cancer-targeted selenium nanoparticles.

              Selenium nanoparticles (SeNPs) have garnered a great deal of attention as potential cancer therapeutic payloads. However, the in vivo targeting drug delivery has been challenging. Herein, we describe the synthesis of tansferrin (Tf)-conjugated SeNPs and its use as a cancer-targeted drug delivery system to achieve enhanced cellular uptake and anticancer efficacy. Tf as targeting ligand significantly enhances the cellular uptake of doxorubicin (DOX)-loaded SeNPs through clathrin-mediated and caveolae/lipid raft-mediated endocytosis in cancer cells overexpressing transferrin receptor, and increases their selectivity between cancer and normal cells. DOX-loaded and Tf-conjugated SeNPs (Tf-SeNPs) exhibits unprecedented enhanced cytotoxicity toward cancer cells through induction of apoptosis with the involvement of intrinsic and extrinsic pathways. Internalized Tf-SeNPs triggers intracellular ROS overproduction, thus activates p53 and MAPKs pathways to promote cell apoptosis. In the nude mice xenograft experiment, Tf-SeNPs significantly inhibits the tumor growth via induction of p53-mediated apoptosis. This cancer-targeted design of SeNPs opens a new path for synergistic treating of cancer with higher efficacy and decreased side effects.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                13 June 2022
                : 16
                : 1811-1825
                [1 ]Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University , Sohag, 82524, Egypt
                [2 ]Department of Pharmaceutics, Faculty of Pharmacy, Assiut University , Assiut, 71526, Egypt
                [3 ]Department of Pharmaceutics, Faculty of Pharmacy, South Valley University , Qena, 83523, Egypt
                Author notes
                Correspondence: Aml I Mekkawy, Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University , Sohag, 82524, Egypt, Email aml.mekkawy@pharm.sohag.edu.eg
                Author information
                © 2022 Mekkawy et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                : 14 February 2022
                : 28 May 2022
                Page count
                Figures: 10, Tables: 2, References: 73, Pages: 15
                Original Research

                Pharmacology & Pharmaceutical medicine
                selenium nanoparticles,soybean lecithin,polyethylene glycol,β-cyclodextrin,indomethacin,synergistic activity,carrageenan


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