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Chamcheu JC, Siddiqui IA, Adhami VM, et al. Int J Nanomedicine. 2018;13:4189–4206. An error during the preparation of Figures 1 and 5 for publishing led to the inadvertent creation of duplicate regions in images from these figures on pages 4194 and 4199, respectively. The journal wishes to apologise for this error. The correct versions of Figures 1 and 5 are as follows: Figure 1 Size characterization and encapsulation and loading efficiencies of chitosan-based nanoEGCG. (A) Size measurement and distribution of nanoEGCGusing dynamic light scattering. (B) Zeta potential measurement of nanoEGCG. (C) Representative transmission electron microscopy photomicrographs showing the relative homogeneous size and morphology of (i) diluted nanoEGCGand (ii) undiluted nanoEGCG, and (iii) CHI-Void-NPs. Scale bar=200 nm; the insets represent higher magnification. (D) Encapsulation and loading efficiency of EGCG on to chitosan nanoparticles as monitored with UV-vis spectra for free EGCG (not encapsulated) and total EGCG (encapsulated + free). (E) UV-vis spectra used to construct the standard curve, with EGCGconcentrations of 25, 12.5, 6.25, 3.12, and 1.6 μg/mL.Abbreviations: EGCG, (–)-epigallocatechin-3-gallate; nanoEGCG, CHI-EGCG-NPs, chitosan-based polymeric nanoparticle formulation of EGCG; CHI-Void-NPs, chitosan-based void (without EGCG) nanoparticles; UV-vis, ultraviolet–visible. Figure 5 Effect of topically applied free EGCG and nanoEGCG on infiltrating immune cells and expression of differentiation markers in IMQ-treated mouse skin lesions: Mice were treated in 4 groups as described in the legends to Figure 4 and Figure S5. (A–D, F–I, K–N, P–S) Photomicrographs showing immunohistological features of: (A–D) mast cells (toluidine blue staining); (F–I) epidermis/dermis (NE, brown staining), and microabscesses (arrow); (K–N) macrophages (F4/80, red staining); and (P–S) double immunofluorescence staining for loricrin (green) and T-lymphocytes (CD4+, red staining). Nuclei were counterstained blue with DAPI. Magnification for all panels ×200. (E, J, O, T, U) Quantitative analyses of changes in immune cells: (E) mast cells; (J) NE+ cells; (O) F4/80+ cells; and (U) loricrin in the 4 treatment groups. Each data point represents the mean±SD of 4 random fields/mouse from 5 mice/group. *p, 0.05, **p, 0.01, ***p, 0.001, and ****p, 0.0001 for the indicated 2-way comparisons.Abbreviations: EGCG, (–)-epigallocatechin-3-gallate; nanoEGCG, chitosan-based polymeric nanoparticle formulation of EGCG; IMQ, imiquimod; NE, neutrophil elastase; LPV, low-power view.

Mohamad EA, Aly AA, Khalaf AA, et al. Drug Des Devel Ther. 2021;15:3151–3162. The Editor and Publisher of Drug Design, Development and Therapy wish to retract the published article. Concerns were raised regarding the integrity of the HPLC chromatograms presented in Figure 1, where the values of the peaks did not appear to correspond with the values shown along the x-axis. The authors did respond to our queries and explained that their laboratory does not have access to an HPLC device and the HPLC experiments were performed by a third-party. They further explained that errors had been made during calculations of the retention times, but they were unable to explain how this occurred. In addition, discrepancies remained in the retention times of the corrected HPLC chromatograms the authors provided, and there was a lack of adequate data associated with these experiments. The Editor determined that the explanation for the calculation errors and availability of original data were both insufficient and had concerns over the reliability of the reported findings. The Editor requested for the article to be retracted and the authors were notified of this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Ebtesam A Mohamad,1 Aya A Aly,2 Aya A Khalaf,2 Mona I Ahmed,2 Reham M Kamel,2 Sherouk M Abdelnaby,2 Yasmine H Abdelzaher,2 Marize G Sedrak,2 Shaker A Mousa3 1Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt; 2Biotechnology/Biomolecular Chemistry Program, Faculty of Science, Cairo University, Giza, Egypt; 3The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USACorrespondence: Shaker A MousaThe Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, 12144, USATel +1-518-694-7397Fax +1-518-694-7567Email shaker.mousa@acphs.eduIntroduction: Skin aging is a normal process that might be accelerated or delayed by altering the balance between antioxidants and free radicals due to increase in the exposure to reactive oxygen species (ROS) into skin cells via UV radiation. Antioxidants can neutralize the harmful effects of ROS, and secondary plant metabolites might help protect against UV radiation.Methods: In this study, punicalagin was extracted from pomegranate, and concentrations of total polyphenolics and flavonoids were determined, and antioxidant activities were measured. Punicalagin was loaded onto niosomes, and its morphology and release were studied. An in vitro study was performed on human fibroblast cell line HFB4 cells with aging induced by H2O2 and UV radiation. Cell cycle arrest was studied, and different genes (MMP3, Col1A1, Timp3, and TERT) involved in the skin aging process were selected to measure punicalagin’s effect.Results: Punicalagin succeeded in reducing the growth arrest of HFB4 cells, activated production of the Col1A1 and Timp3 genes, maintained collagen level, and lowered MMP3. Punicalagin increased human TERT concentration in skin cells.Discussion: Punicalagin is promising as a natural antioxidant to protect human skin from aging.Keywords: skin aging, punicalagin, niosomes, UV radiation, collagen

Naif A Al-Gabri,1,2 Sultan AM Saghir,3 Sallah A Al-Hashedi,4 Ali H El-Far,5 Asmaa F Khafaga,6 Ayman A Swelum,7 Abdullah S Al-wajeeh,8 Shaker A Mousa,9 Mohamed E Abd El-Hack,10 Mohammed AE Naiel,11 Khaled A El-Tarabily12,13 1Department of Pathology, Faculty of Veterinary Medicine, Thamar University, Dhamar, Yemen; 2Laboratory of Regional Djibouti Livestock Quarantine, Abu Yasar international Est. 1999, Arta, Djibouti; 3Department of Medical Analysis, Princess Aisha Bint Al-Hussein College of Nursing and Medical Sciences, AlHussein Bin Talal University, Ma’an, 71111, Jordan; 4Central Labs, King Faisal University, Al-Ahsa, Saudi Arabia; 5Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, Egypt; 6Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, Edfina, 22758, Egypt; 7Department of Theriogenology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44511, Egypt; 8Anti-Doping Lab Qatar, Doha, Qatar; 9Department of Pharmaceutical Sciences, the Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, 12144, USA; 10Poultry Department, Faculty of Agriculture, Zagazig University, Zagazig, 44519, Egypt; 11Animal Production Department, Faculty of Agriculture, Zagazig University, Zagazig, 44519, Egypt; 12Department of Biology, College of Science, United Arab Emirates University, Al-Ain, 15551, United Arab Emirates; 13Biosecurity and One Health Research Centre, Harry Butler Institute, Murdoch University, Murdoch, Western Australia, 6150, AustraliaCorrespondence: Khaled A El-Tarabily Email ktarabily@uaeu.ac.aeAbstract: As a crucial organ, the lung is exposed to various harmful agents that may induce inflammation and oxidative stress, which may cause chronic or acute lung injury. Nigella sativa, also known as black seed, has been widely used to treat various diseases and is one of the most extensively researched medicinal plants. Thymoquinone (TQ) is the main component of black seed volatile oil and has been proven to have antioxidant, anti-inflammatory, and antineoplastic properties. The potential therapeutic properties of TQ against various pulmonary disorders have been studied in both in vitro and in vivo studies. Furthermore, the application of nanotechnology may increase drug solubility, cellular absorption, drug release (sustained or control), and drug delivery to lung tissue target sites. As a result, fabricating TQ as nanoparticles (NPs) is a potential therapeutic approach against a variety of lung diseases. In this current review, we summarize recent findings on the efficacy of TQ and its nanotypes in lung disorders caused by immunocompromised conditions such as cancer, diabetes, gastric ulcers, and other neurodegenerative diseases. It is concluded that TQ nanoparticles with anti-inflammatory, antioxidant, antiasthma, and antitumor activity may be safely applied to treat lung disorders. However, more research is required before TQ nanoparticles can be used as pharmaceutical preparations in human studies.Keywords: anticancer activity, antimicrobial activity, bioavailability, drug delivery, molecular potential, lung disease, nanoparticle, thymoquinone

Salaheldin TA, Loutfy SA, Ramadan MA, Youssef T, Mousa SA. Int J Nanomedicine. 2019;14:4397–4412. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the alleged duplication of TEM images in Figure 7A and 7C. In addition, it also appears that parts of the gel electrophoresis image shown in Figure S2 was published previously in Figure 6 from an article in the Asian Pacific Journal of Cancer Prevention (Loutfy et al, 2017 ‘Synthesis, Characterization and Cytotoxic Evaluation of Graphene Oxide Nanosheets: In Vitro Liver Cancer Model’ 10.22034/APJCP.2017.18.4.955). Both gel electrophoresis images describe lanes representing different experimental conditions. The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged duplication, nor were they able to provide adequate original data that could verify the reported findings. The Editor requested to retract the article and the authors were notified of this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Samah A Loutfy,1,2 Mostafa H Elberry,1 Khaled Yehia Farroh,3 Hossam Taha Mohamed,4,5 Aya A Mohamed,4 ElChaimaa B Mohamed,1 Ahmed Hassan Ibrahim Faraag,6 Shaker A Mousa7 1Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 2Nanotechnology Research Center, British University, Cairo, Egypt; 3Nanotechnology and Advanced Materials Central Lab, Agricultural Research Center, Giza, Egypt; 4Faculty of Biotechnology, October University for Modern Sciences and Arts, 6th October, Giza, Egypt; 5Department of Zoology, Faculty of Science,Cairo University, Giza, Egypt; 6Botany and Microbiology Department, Bioinformatics Center, Faculty of Science, Helwan University, Cairo, Egypt; 7The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USACorrespondence: Samah A LoutfyVirology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr El Eini, Fom El-Khalig, Cairo 11796, EgyptTel +20 1222840964Email Samah.loutfy@gmail.comPurpose: Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7.Methods: Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot.Results: The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of -124.91, -159.02, and -129.16, for curcumin respectively, and -68.51, -54.52, and -157.63 for CuCs nanocomposite, respectively. CuCs nanocomposite was prepared at sizes 29– 39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8 μg/mL for curcumin and 25 μg/mL for the nanocomposite on Huh7 but was 25.8 μg/mL and 34 μg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes’ expression revealed the caspase-dependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibition of viral entry and replication, which was confirmed with HCV core protein expression.Conclusion: CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent.Keywords: caspase-dependent pathway, chitosan curcumin nanocomposite, hepatitis C virus genotype 4a, Huh7, docking

Deena S Mousa,1 Ali H El-Far,2 Amna A Saddiq,3 Thangirala Sudha,4 Shaker A Mousa4 1Yale University, New Haven, CT, USA; 2Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt; 3Faculty of Science, Department of Biology, University of Jeddah, Jeddah 21589, Saudi Arabia; 4Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USACorrespondence: Shaker A MousaProfessor of Pharmacology, Albany College of Pharmacy and Health Sciences, Chairman and Executive Vice President, The Pharmaceutical Research Institute, One Discovery Drive, Rensselaer, New York 12144, USAEmail shaker.mousa@acphs.eduPurpose: This study was designed to determine the potential effect of nanoencapsulated bioactive compounds from different natural sources on human pancreatic cancer.Background: Pancreatic cancer carries the highest fatality rate among all human cancers because of its high metastatic potential and late presentation at the time of diagnosis. Hence there is a need for improved methods to prevent and treat it. Natural products, such as 3, 3′-diindolylmethane (DIM) and ellagic acid (EA) demonstrated anticancer efficacy against various cancer types. However, DIM is insoluble. Hence, using nanotechnology to encapsulate these compounds in combination with EA might improve their physical and chemical properties and their delivery to the cancer cells.Methods: Human pancreatic cancer cells, namely SUIT2-luciferase transfected, were used to examine the effects of DIM or EA and their nanoformulation in poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) [PLGA-PEG] nanoparticles (NPs) on SUIT2-luciferase cell viability/proliferation over 24 hrs. Additionally, effects on tumor weight and angiogenesis were determined using the chick chorioallantoic membrane (CAM) tumor implant model.Results: Both DIM and EA PLGA-PEG NPs resulted in rapid suppression of pancreatic cancer cell viability/proliferation within 24 hrs (P < 0.01), while the non-encapsulated DIM and EA did not show any significant effect on SUIT2 cancer cell viability or cell proliferation (MTT assay). In the CAM pancreatic cancer cell (SUIT2) implant model, results showed a greater suppression of tumor weight (P < 0.01), tumor cell viability, and tumor angiogenesis (P < 0.01) for DIM NPs and EA NPs and their combinations versus DIM or EA alone.Conclusion: Nanoformulation of DIM and EA resulted in a more effective suppression of pancreatic cancer cell viability, pancreatic tumor weight, implanted cancer cell viability, and tumor angiogenesis as compared with these bioactive compounds alone.Keywords: pancreatic cancer, 3, 3′-diindolylmethane, ellagic acid, PLGA-PEG nanoparticles, anti-angiogenesis, chick chorioallantoic membrane model

Mousa DS, El-Far AH, Saddiq AA, Sudha T, Mousa SA. Int J Nanomedicine. 2020;15:2259‒2268. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the alleged duplication of images in Figure 5 with those in figures from two other publications which have common authors. Specifically, Figure 5, Matrigel/SUIT2+EA (1 µg), appears to have been duplicated with the same image in Figure 2A, FGF2 and Figure 4A, GC-1 from Mousa et al (2005), Journal of Cardiovascular Pharmacology (doi: 10.1097/01.fjc.0000175438.94906.a0). Figure 5, Matrigel/SUIT2+EA NPs (1 µg)+DIM NPs (1 µg), appears to have been duplicated with Figure 5, FGF+Difluoroallicin (12;4 µg) from Block et al (2017), Molecules (https://doi.org/10.3390/molecules22122081) and Figure 2A, PBS Control from Mousa et al (2005), Journal of Cardiovascular Pharmacology (doi: 10.1097/01.fjc.0000175438.94906.a0). The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged duplication that would support the integrity of their research. The decision was made to retract the article and the authors do not agree with this. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Loutfy SA, Elberry MH, Farroh KY, et al. Int J Nanomedicine. 2020;15:2699–2715. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the alleged duplication of images in Figure 8. The authors responded to our queries and explained the western blot experiments were performed by a commercial laboratory; however, they were unable to provide all the original data. The data that was provided showed inconstancies between what was considered original western blot data and what was shown in Figure 8. This raised concerns over the reliability and validity of the findings and the Editor requested for the article to be retracted and the authors do not agree with this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Abou-El-Naga AM, Mutawa G, El-Sherbiny IM, Mousa SA. Int J Nanomedicine. 2018;13:8153-8164. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the alleged manipulation of gel electrophoresis images in Figure 6A which appeared to show the bands had been spliced together. The authors responded to our queries and confirmed the original gel images had been spliced for clarity. However, the authors were unable to provide the original data for the gel electrophoresis experiments and could not verify the original results or findings. The decision was made to retract the article and the authors agreed with this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Samar A Shahein1,* Ahmed M Aboul-Enein,1 Iman M Higazy,2 Faten Abou-Elella,1 Witold Lojkowski,3 Esam R Ahmed,4 Shaker A Mousa,5 Khaled AbouAitah3,6,*1Biochemistry Department, Faculty of Agriculture, Cairo University, Giza, Egypt; 2Department of Pharmaceutical Technology, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Giza, Egypt; 3Laboratory of Nanostructures, Institute of High Pressure Physics, Polish Academy of Sciences, Warsaw, Poland; 4Confirmatory Diagnostic Unit, Egyptian Organization for Vaccine, Sera and Biological Products (VACSERA), Giza, Egypt; 5The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, New York, NY, USA; 6Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Giza, Egypt*These authors contributed equally to this workBackground and purpose: Glioma is one of the most aggressive primary brain tumors and is incurable. Surgical resection, radiation, and chemotherapies have been the standard treatments for brain tumors, however, they damage healthy tissue. Therefore, there is a need for safe anticancer drug delivery systems. This is particularly true for natural prodrugs such as thymoquinone (TQ), which has a high therapeutic potential for cancers but has poor water solubility and insufficient targeting capacity. We have tailored novel core-shell nanoformulations for TQ delivery against glioma cells using mesoporous silica nanoparticles (MSNs) as a carrier.Methods: The core-shell nanoformulations were prepared with a core of MSNs loaded with TQ (MSNTQ), and the shell consisted of whey protein and gum Arabic (MSNTQ-WA), or chitosan and stearic acid (MSNTQ-CS). Nanoformulations were characterized, studied for release kinetics and evaluated for anticancer activity on brain cancer cells (SW1088 and A172) and cortical neuronal cells-2 (HCN2) as normal cells. Furthermore, they were evaluated for caspase-3, cytochrome c, cell cycle arrest, and apoptosis to understand the possible anticancer mechanism.Results: TQ release was pH-dependent and different for core and core-shell nanoformulations. A high TQ release from MSNTQ was detected at neutral pH 7.4, while a high TQ release from MSNTQ-WA and MSNTQ-CS was obtained at acidic pH 5.5 and 6.8, respectively; thus, TQ release in acidic tumor environment was enhanced. The release kinetics fitted with the Korsmeyer–Peppas kinetic model corresponding to diffusion-controlled release. Comparative in vitro tests with cancer and normal cells indicated a high anticancer efficiency for MSNTQ-WA compared to free TQ, and low cytotoxicity in the case of normal cells. The core-shell nanoformulations significantly improved caspase-3 activation, cytochrome c triggers, cell cycle arrest at G2/M, and apoptosis induction compared to TQ.Conclusion: Use of MSNs loaded with TQ permit improved cancer targeting and opens the door to translating TQ into clinical application. Particularly good results were obtained for MSNTQ-WA.Keywords: brain cancer targeting, drug delivery system, thymoquinone core-shell nanoformulation, mesoporous silica nanoparticles, pH-dependent release kinetics

Taher A Salaheldin,1,2 Samah A Loutfy,3 Marwa A Ramadan,4 Tareq Youssef,4 Shaker A Mousa11Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA; 2Nanotechnology and Advanced Materials Central Lab, Agricultural Research Center, Giza, Egypt; 3Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 4Department of Photochemistry Photobiology, National Institute for Laser Enhanced Science (NILES) Cairo University, Cairo, EgyptBackground: Graphene magnetite nanocomposites (G/Fe3O4) exhibit light photothermal conversion upon enhancement by 808 nm IR laser excitation. We evaluated the cytotoxic and photothermal effects of G/Fe3O4 on a HepG2 human liver cancer cell model.Methods: Graphene nanosheets (rGO), magnetite nanoparticles (Fe3O4), and G/Fe3O4 were prepared by chemical methods and characterized using transmission electron microscopy, Raman spectroscopy, zeta analysis, and vibrating sample magnemeter. Dark and light cytotoxicity were screened with colorimetric Sulforhodamine B cell viability assay after 24 and 48 hours. DNA fragmentation and some apoptotic genes on a transcriptional RNA level expression were performed. All prepared nanomaterials were evaluated for their photothermal effect at concentrations of 10 and 50 μg/mL. The power density incident on the cells by 300 mW 808 IR diode laser was 0.597 W/cm2,.Results: Treatment of HepG2 with 400 μg/mL of rGO, Fe3O4, and G/Fe3O4 showed alteration in cell morphology after 24 hours of cell treatment and revealed toxic effects on cellular DNA. Evaluation of the cytotoxic effects showed messenger RNA (mRNA) in β-actin and Bax apoptotic genes, but no expression of mRNA of caspase-3 after 24 hours of cell exposure, suggesting the involvement of an intrinsic apoptotic caspase-independent pathway. A photothermal effect was observed for G/Fe3O4 after irradiation of the HepG2 cells. A marked decrease was found in cell viability when treated with 10 and 50 μg/mL G/Fe3O4 from 40% to 5% after 48 hours of cell treatment.Conclusion: Results indicate that G/Fe3O4 nanocomposite was effective at transformation of light into heat and is a promising candidate for cancer therapy.Keywords: graphene magnetite nanocomposite, HepG2 human liver cancer, cytotoxicity, photothermal effect, PCR

Amoura M Abou-El-Naga,1 Ghada Mutawa,2 Ibrahim M El-Sherbiny,3 Shaker A Mousa4 1Zoology Department, Faculty of Sciences, Mansoura University, Mansoura 35516, Egypt; 2Department of Basic Science, Faculty of Dentistry, Horus University in Egypt (HUE), New Damietta 34517, Egypt; 3Center for Materials Science, Zewail City of Science and Technology, Cairo 12588, Egypt; 4The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA Background: Successfully overcoming obstacles due to anticancer drugs’ toxicity and achieving effective treatment using unique nanotechnology is challenging. The complex nature of breast tumors is mainly due to chemoresistance. Successful docetaxel (DTX) delivery by nanoparticles (NPs) through inhibition of multidrug resistance (MDR) can be a bridge to enhance intracellular dose and achieve higher cytotoxicity for cancer cells. Purpose: This study tested primary patient breast cancer cells in vitro with traditional free DTX in comparison with polymeric nanocarriers based on poly lactic co-glycolic acid (PLGA) NPs. Materials and methods: Establishment of primary cell line from breast malignant tumor depends on enzymatic digestion. Designed DTX-loaded PLGA NPs were prepared with a solvent evaporation method; one design was supported by the use of folic acid (FA) conjugated to PLGA. The physical properties of NPs were characterized as size, charge potential, surface morphology, DTX loading, and encapsulation efficiency. In vitro cellular uptake of fluorescent NPs was examined visually with confocal fluorescence microscopy and quantitatively with flow cytometry. In vitro cytotoxicity of all DTX designed NPs against cancer cells was investigated with MTT assay. RT-PCR measurements were done to examine the expression of chemoresistant and apoptotic genes of the tested DTX NPs. Results: Cellular uptake of DTX was time dependent and reached the maximum after loading on PLGA NPs and with FA incorporation, which activated the endocytosis mechanism. MTT assay revealed significant higher cytotoxicity of DTX-loaded FA/PLGA NPs with higher reduction of IC50 (8.29 nM). In addition, PLGA NPs, especially FA incorporated, limited DTX efflux by reducing expression of ABCG2 (3.2-fold) and MDR1 (2.86-fold), which were highly activated by free DTX. DTX-loaded FA/PLGA NPs showed the highest apoptotic effect through the activation of Caspase-9, Caspase-3, and TP53 genes by 2.8-, 1.6-, and 1.86-fold, respectively. Conclusion: FA/PLGA NPs could be a hopeful drug delivery system for DTX in breast cancer treatment. Keywords: PLGA NPs, chemoresistance, endocytosis, drug delivery system, active targeting, human breast cancer, DTX loaded PLGA NPs

Jean Christopher Chamcheu,1,2,* Imtiaz A Siddiqui,1,* Vaqar M Adhami,1,* Stephane Esnault,3 Dhruba J Bharali,4 Abiola S Babatunde,1,5 Stephanie Adame,1 Randall J Massey,6 Gary S Wood,1 B Jack Longley,1 Shaker A Mousa,4 Hasan Mukhtar11Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, and the Middleton VA Medical Center, Madison, WI, USA; 2Department of Basic Pharmaceutical Sciences, School of Pharmacy, College of Health and Pharmaceutic Sciences, University of Louisiana at Monroe, Monroe, LA, USA; 3Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, The University of Wisconsin–Madison School of Medicine and Public Health, Madison, WI, USA; 4The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; 5Department of Hematology, University of Ilorin, Ilorin, Nigeria; 6Electron Microscope Facility, Medical School Research Support Progs, School of Medicine and Public Health, University of Wisconsin, and the Middleton VAMedical Center, Madison, WI, USA *These authors contributed equally to this work Background: Psoriasis is a chronic and currently incurable inflammatory skin disease characterized by hyperproliferation, aberrant differentiation, and inflammation, leading to disrupted skin barrier function. The use of natural agents that can abrogate these effects could be useful for the treatment of psoriasis. Earlier studies have shown that treatment of keratinocytes and mouse skin with the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) mitigated inflammation and increased the expression of caspase-14 while promoting epidermal differentiation and cornification. However, bioavailability issues have restricted the development of EGCG for the treatment of psoriasis.Materials and methods: To overcome these limitations, we employed a chitosan-based polymeric nanoparticle formulation of EGCG (CHI-EGCG-NPs, hereafter termed nanoEGCG) suitable for topical delivery for treating psoriasis. We investigated and compared the efficacy of nanoEGCG versus native or free EGCG in vitro and in an in vivo imiquimod (IMQ)-induced murine psoriasis-like dermatitis model. The in vivo relevance and efficacy of nanoEGCG formulation (48 µg/mouse) were assessed in an IMQ-induced mouse psoriasis-like skin lesion model compared to free EGCG (1 mg/mouse).Results: Like free EGCG, nanoEGCG treatment induced differentiation, and decreased proliferation and inflammatory responses in cultured keratinocytes, but with a 4-fold dose advantage. Topically applied nanoEGCG elicited a significant (p20-fold dose advantage over free EGCG.Conclusion: Based on these observations, our nanoEGCG formulation represents a promising drug-delivery strategy for treating psoriasis and possibly other inflammatory skin diseases. Keywords: chitosan nanoparticles, topical delivery of chitosan nanoformulated EGCG, psoriasis-like skin inflammation, phytochemical treatment of psoriasis, normal human epidermal keratinocytes, differentiation, anti-inflammatory action

Loutfy SA, Elberry MH, Farroh KY, et al. Int J Nanomedicine. 2020;15:2699–2715.The authors have advised Figure 8 on page 2712 is incorrect. The correct Figure 8 is shown below.The authors apologize for this error and advise it does not affect the results of the paperRead the original article

Thangirala Sudha,1 Dhruba J Bharali,1 Murat Yalcin,1,2 Noureldien HE Darwish,1,3 Melis Debreli Coskun,1,4 Kelly A Keating,1 Hung-Yun Lin,5,6 Paul J Davis,1,7 Shaker A Mousa1 1The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA; 2Department of Physiology, Veterinary Medicine Faculty, Uludag University, Gorukle, Bursa, Turkey; 3Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 4Department of Biology, Faculty of Arts and Sciences, Uludag University, Gorukle, Bursa, Turkey; 5PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, 6Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan; 7Department of Medicine, Albany Medical College, Albany, NY, USA Abstract: The tetraiodothyroacetic acid (tetrac) component of nano-diamino-tetrac (NDAT) is chemically bonded via a linker to a poly(lactic-co-glycolic acid) nanoparticle that can encapsulate anticancer drugs. Tetrac targets the plasma membrane of cancer cells at a receptor on the extracellular domain of integrin αvβ3. In this study, we evaluate the efficiency of NDAT delivery of paclitaxel and doxorubicin to, respectively, pancreatic and breast cancer orthotopic nude mouse xenografts. Intra-tumoral drug concentrations were 5-fold (paclitaxel; P

Amit B Shirode,1,2,* Dhruba J Bharali,3,* Sameera Nallanthighal,1,2 Justin K Coon,1,2 Shaker A Mousa,3 Ramune Reliene1,2 1Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, NY, USA; 2Cancer Research Center, University at Albany, Rensselaer, NY, USA; 3Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA *These authors contributed equally to this work Abstract: Pomegranate polyphenols are potent antioxidants and chemopreventive agents but have low bioavailability and a short half-life. For example, punicalagin (PU), the major polyphenol in pomegranates, is not absorbed in its intact form but is hydrolyzed to ellagic acid (EA) moieties and rapidly metabolized into short-lived metabolites of EA. We hypothesized that encapsulation of pomegranate polyphenols into biodegradable sustained release nanoparticles (NPs) may circumvent these limitations. We describe here the development, characterization, and bioactivity assessment of novel formulations of poly(D,L-lactic-co-glycolic acid)–poly(ethylene glycol) (PLGA–PEG) NPs loaded with pomegranate extract (PE) or individual polyphenols such as PU or EA. Monodispersed, spherical 150–200 nm average diameter NPs were prepared by the double emulsion–solvent evaporation method. Uptake of Alexa Fluor-488-labeled NPs was evaluated in MCF-7 breast cancer cells over a 24-hour time course. Confocal fluorescent microscopy revealed that PLGA–PEG NPs were efficiently taken up, and the uptake reached the maximum at 24 hours. In addition, we examined the antiproliferative effects of PE-, PU-, and/or EA-loaded NPs in MCF-7 and Hs578T breast cancer cells. We found that PE, PU, and EA nanoprototypes had a 2- to 12-fold enhanced effect on cell growth inhibition compared to their free counterparts, while void NPs did not affect cell growth. PU-NPs were the most potent nanoprototype of pomegranates. Thus, PU may be the polyphenol of choice for further chemoprevention studies with pomegranate nanoprototypes. These data demonstrate that nanotechnology-enabled delivery of pomegranate polyphenols enhances their anticancer effects in breast cancer cells. Thus, pomegranate polyphenols are promising agents for nanochemoprevention of breast cancer. Keywords: PLGA–PEG nanoparticles, pomegranate extract, punicalagin, ellagic acid, MCF-7 cells, Hs578T cells

Michael Thomas,1 Shaymaa S Mousa,2 Shaker A Mousa1 1Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; 2The Johns Hopkins University, Baltimore, MD, USA Abstract: Wet age-related macular degeneration (AMD) is the most common reason for vision loss in the United States. Many treatments, such as laser therapy and photodynamic therapies, have been used but their efficacy is limited. Emerging anti-vascular endothelial growth factor (VEGF) therapies are now considered the standard of care. Anti-VEGF agents inhibit angiogenesis in the eye by suppressing abnormal blood vessel growth, leading to vision improvement. Ranibizumab and bevacizumab are two examples of anti-VEGF drugs that have been approved; both showed promise based on the visual acuity scale. Aflibercept, another new therapy known to trap VEGF and inhibit multiple growth factors, is promising not only because it can be taken bimonthly based on year 1 of the VIEW trials, but it can also be extended, as demonstrated in year 2 of the VIEW trials. Based on a cost–effect analysis, aflibercept is comparable to other leading therapies. This is a review of relevant clinical trials that have proven the non-inferiority and safety of aflibercept compared to the standard of care and its unique role in the current management of wet AMD. Keywords: aflibercept, VEGF, anti-VEGF, pegatanib, bevacizumab, ranibizumab, VIEW trials

Gabriel Beidoe, Shaker A MousaPharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USAAbstract: Primary open-angle glaucoma (POAG) is a leading cause of blindness with no known cure. Management of the disease focuses on lowering intraocular pressure (IOP) with current classes of drugs like prostaglandin analogs, beta-blockers, alpha-agonists, and carbonic anhydrase inhibitors. These treatments have not helped all patients. Some patients continue to experience deterioration in the optic nerve even though their IOPs are within the normal range. New views have surfaced about other pathophysiological processes (such as oxidative stress, vascular dysfunction, and retinal cell apoptosis) being involved in POAG progression, and adjunctive treatments with drugs like memantine, bis(7)-tacrine, nimodipine, and mirtogenol are advocated. This review examines the current and proposed treatments for POAG. Some of the proposed drugs (bis(7)-tacrine, nimodipine, vitamin E, and others) have shown good promise, mostly as monotherapy in various clinical trials. It is recommended that both the current and proposed drugs be put through further robust trials in concurrent administration and evaluated.Keywords: bis(7)-tacrine, betaxolol, memantine, mirtogenol, POAG, timolol, travoprost

Asperger's syndrome (AS), a behavioral disorder that is related to autism, is associated with abnormal social functioning and repetitive behaviors but not with a decrease in intelligence or linguistic functionality. This article reviews the clinical diagnosis of AS and discusses the comorbid disorders that may be present with AS, as well as the efficacy, safety, and tolerability of pharmacotherapies given to AS patients, as reported in preclinical and clinical studies. AS may be present with several comorbid disorders including: attention deficit hyperactivity disorder, anxiety, schizophrenia, bipolar disorder, depression, and Tourette's syndrome. The difficulty in distinguishing AS from autism results in treating the comorbid disorder symptoms, rather than treating the symptoms of AS. Accordingly, there is a great need to further understand the psychobiology of AS and its association with other disorders, which should expand the pharmacological and non-pharmacological therapeutic options and improve the quality of life for AS patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Red Yeast Rice (RYR) is a traditional Chinese food that is fermented and obtained after red yeast (Monascus purpureus) is grown on rice. RYR contains Monacolin K (Lovastatin) and other active ingredients that are thought to play a role in the management of cholesterol levels. Recently, many clinical trials have focused on the uses of RYR, including for dyslipidemia, coronary heart disease, diabetes, osteoporosis, cancer, non-alcoholic fatty liver disease, fatigue, and memory. OBJECTIVES: The primary objective of this review is to evaluate the effectiveness of RYR on the management of dyslipidemia. The secondary objective is to review studies that focus on the other uses of RYR. The following search terms were used: red yeast rice, Xuezhikang, Hypocol, Cholestin, Monascus purpureus combined with dyslipidemia, hypercholesterolemia, hyperlipidemia, lipid, cardiovascular, coronary, atherosclerosis, diabetes, sugar, bone, osteoporosis, liver, fatigue, memory, Alzheimer's, dementia. RESULTS: Studies reviewed show that RYR significantly lowered LDL cholesterol and total cholesterol. Effects on triglycerides and HDL cholesterol were also observed in some studies. Compared with statins, RYR was shown to have an equal efficacy to statins when combined with or without other dietary supplements. RYR also appeared to be superior to placebo in preventing nonfatal myocardial infarction, total coronary heart disease events, and total deaths. On the other hand, information on diabetes, osteoporosis, cancer, non-alcoholic fatty liver disease, fatigue, and memory are currently limited although in vivo and in vitro studies have shown an effect. CONCLUSION: Results of RYR clinical trials presented here have limitations and RYR's clinical use should be further investigated before using RYR as one of the alternative treatments for dyslipidemia management, despite the fact that the strongest evidence for RYR use is in dyslipidemia versus other clinical conditions. [ABSTRACT FROM AUTHOR]

Alliin, a compound derived from garlic, demonstrated dose-dependent inhibition of fibroblast growth factor-2 (FGF2)-induced human endothelial cell (EC) tube formation and angiogenesis in the chick chorioallantoic membrane (CAM) model. Additionally, alliin demonstrated potent inhibition of vascular endothelial growth factor (VEGF)-induced angiogenesis in the CAM model. The antioxidant vitamins C and E significantly (P < 0.001) enhanced the inhibitory efficacy of alliin on FGF2-induced EC tube formation and angiogenesis. Alliin significantly increased (P < 0.01) nitric oxide (NO) release into the CAM fluid, which was further enhanced by vitamins C and E. The NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME) reversed the anti-angiogenesis efficacy of alliin in the CAM model. Vitamins C and E significantly enhanced the anticancer efficacy of alliin in inhibiting colon and fibrosarcoma tumor growth. Alliin significantly inhibited both FGF2 and VEGF secretion from human fibrosarcoma cells in a concentration-dependent manner. Additionally, alliin up-regulated the p53 production in FGF2-stimulated EC. These data indicated a synergistic effect of antioxidants on the anti-angiogenesis and anticancer efficacy of alliin. These data also suggest the implication of cellular NO and p53 as mediators of anti-angiogenesis and anticancer effects of alliin. [ABSTRACT FROM AUTHOR]