Ezzat, N., N. Emadeldien, M. K. Ali, S. Fahd, S. Shebl, M. Elshishiny, M. R. Gedamy, N. Hassan, S. M. A. Soliman, and E. M. Elzayat, "In vitro Evaluation of Zinc Oxide-Metformin Folic Acid Nanocomposite as a Targeted Drug Delivery System for Cancer Therapy.", Asian Pacific journal of cancer prevention : APJCP, vol. 26, issue 2, pp. 443-452, 2025 Feb 01. Abstract

BACKGROUND: Cancer has become the second cause of death worldwide after cardiovascular diseases. Thus, the development of efficient therapeutic approaches for cancer treatment seems necessary. One of the promising approaches is depending on nanotechnology in terms of drug delivery systems. ZnO nanoparticles have been approved for their efficiency as a drug delivery system due to their unique properties. Metformin (1, 1-dimethylbiguanide hydrochloride) is widely used as an anti-diabetic drug. However, recent studies have explored its repurposing as an anti-cancer drug.

OBJECTIVE: The present study aims to evaluate the feasibility and efficiency of a folic acid-metformin ZnO nanoparticle delivery system in the treatment of melanoma and bladder cancer cell lines.

METHODS: ZnO nanoparticles were chemically synthesized, loaded with metformin, and conjugated with folic acid at concentrations of 3% and 5%. Characterization of the nanoparticles was conducted using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), zeta potential analysis, and transmission electron microscopy (TEM). The cytotoxicity of ZnO nanoparticles was evaluated against human melanoma (A375) and bladder cancer (T24) cell lines via the MTT assay, with the determination of the half-maximal inhibitory concentration (IC50).

RESULTS: ZnO nanoparticles were successfully synthesized with a spherical shape, size < 20 nm, and high homogeneity. Encapsulation efficiency of metformin on ZnO nanoparticles ranged from 95% to 98%. The folic acid-metformin ZnO nanoparticles demonstrated significant cytotoxic effects against both A375 and T24 cell lines in a dose-dependent manner. The IC50 values revealed higher sensitivity of T24 bladder cancer cells compared to A375 melanoma cells.

CONCLUSION: Overall, our study highlights the promise of the ZnO-metformin-folic acid nanoparticles as an efficient drug delivery system for cancer treatment. These results open up a potentially valuable line of novel therapeutic applications.

El-Naggar, M. E., K. Wael, B. A. Hemdan, A. M. Abdelgawad, M. Z. Elsabee, E. M. El-Zayat, M. A. Hady, and M. M. Hashem, "Chitosan microflower-embedded gelatin sponges for advanced wound management and hemostatic applications.", International journal of biological macromolecules, vol. 276, issue Pt 1, pp. 133749, 2024 Sep. Abstract

The study explored the antimicrobial, antibiofilm, and hemostatic properties of chitosan microflowers (CMF) in sponge form. The main objective was to enhance the preparation of CMF by employing varying quantities of calcium chloride (CaCl) and tripolyphosphate (TPP). CMF was then combined with gelatin (GE) in different proportions to produce three sponge samples: CMF0@GE, CMF1@GE, and CMF2@GE. The CMF had a morphology like that of a flower and produced surfaces with a porous sponge-like structure. The antibacterial activity, as determined by the zone of inhibition (ZOI), increased with greater doses of CMF. Among the tested samples, CMF2@GE had the greatest activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecium. CMF2@GE successfully suppressed biofilm formation, decreased clotting time to an average of 212.67 s, and exhibited excellent biocompatibility by preserving over 90 % viability of human skin fibroblast cells at dosages below 100 μg/mL. The results indicated that gelatin sponges filled with CMF have considerable promise as flexible medical instruments for wound healing and infection control.

Abd El Rahiem, R., S. A. A. Ibrahim, H. Effat, M. E. El-Houseini, R. A. Osman, A. AbdelRaouf, and E. M. Elzayat, "Curcumin, Piperine and Taurine Combination Enhances the Efficacy of Transarterial Chemoembolization Therapy in patients with Intermediate Stage Hepatocellular Carcinoma: A Pilot Study.", Asian Pacific journal of cancer prevention : APJCP, vol. 25, issue 5, pp. 1589-1598, 2024 May 01. Abstract

INTRODUCTION: Diagnosis of the majority of hepatocellular carcinoma (HCC) patients occurs at intermediate to advanced stages, with a few curative therapeutic options being available. It is therefore strongly urgent to discover additional adjuvant therapy for this lethal malignancy. This study aimed to assess the effectiveness of curcumin (C), piperine (P) and taurine (T) combination as adjuvant agents on serum levels of IFN-γ, immunophenotypic and molecular characterization of mononuclear leukocytes (MNLs) in HCC patients treated with Transarterial chemoembolization (TACE).

PATIENTS AND METHODS: Serum and MNLs were collected from 20 TACE-treated HCC patients before (baseline-control samples) and after treatment with 5 g curcumin capsules , 10 mg piperine and 0.5 mg taurine taken daily for three consecutive months. Immunophenotypic and molecular characterization of MNLs were determined by flow cytometry and quantitative real time PCR, respectively. In addition, serum IFN-γ level was quantified by ELISA.

RESULTS: After receiving treatment with CPT combination, there was a highly significant increase in IFN- γ levels in the sera of patients when compared to basal line control samples. Additionally, the group receiving combined therapy demonstrated a downregulation in the expression levels of PD-1, in MNLs as compared to controls. MNLs' immunophenotyping revealed a significant decline in CD4+CD25+cells (regulatory T lymphocytes). Furthermore, clinicopathological characteristics revealed a highly significant impact of CPT combination on aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alpha feto protein (AFP) levels.

CONCLUSION: This study introduces a promising adjuvant CPT combined treatment as natural agents to enhance the management of HCC patients who are candidates to TACE treatment.

Osama, L., H. T. Handal, S. A. M. El-Sayed, E. M. Elzayat, and M. Mabrouk, "Fabrication and Optimisation of Alumina Nanoporous Membranes for Drug Delivery Applications: A Comparative Study.", Nanomaterials (Basel, Switzerland), vol. 14, issue 13, 2024 Jun 24. Abstract

Neurodegenerative disorders cause most physical and mental disabilities, and therefore require effective treatment. The blood-brain barrier (BBB) prevents drug molecules from crossing from the blood to the brain, making brain drug delivery difficult. Implantable devices could provide sustained and regulated medication to solve this problem. Two electrolytes (0.3 M oxalic acid and 0.3 M sulphuric acid) were used to anodise AlO nanoporous membranes, followed by a third anodisation in concentrated HSO to separate the through-hole membranes from the aluminium substrate. FTIR, AFM, and SEM/EDX were used to characterise the membranes' structure and morphology. The effects of the anodisation time and electrolyte type on the AAO layer pore density, diameter, interpore distance, and thickness were examined. As a model drug for neurodegenerative disorders, donepezil hydrochloride (DHC) was loaded onto thin alumina nanoporous membranes. The DHC release profiles were characterised at two concentrations using a UV-Vis spectrophotometer. Oxalic acid membranes demonstrated an average pore diameter of 39.6-32.5 nm, which was two times larger than sulphuric acid membranes (22.6-19.7 nm). After increasing the anodisation time from 3 to 5 h, all of the membranes showed a reduction in pore diameter that was stable regardless of the electrolyte type or period. Drug release from oxalic acid-fabricated membranes was controlled and sustained for over 2 weeks. Thus, nanoporous membranes as implantable drug delivery systems could improve neurodegenerative disease treatment.

Abdelaal, N., M. A. Ragheb, H. M. Hassaneen, E. M. Elzayat, and I. A. Abdelhamid, "Design, in silico studies and biological evaluation of novel chalcones tethered triazolo[3,4-a]isoquinoline as EGFR inhibitors targeting resistance in non-small cell lung cancer.", Scientific reports, vol. 14, issue 1, pp. 26647, 2024 Nov 04. Abstract

A novel series of six [1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-ones (3a-3f) was designed and synthesized. They were characterized based on spectral and elemental analyses. In silico studies were also committed to provide insights and a better understanding of their structural features. The six compounds were screened for their antiproliferative activity using the MTT assay against five human cancer cell lines, namely, A549, HCT116, PC3, HT29, and MCF-7 in parallel with the non-cancerous human lung cell line WI-38. The results showed that 3e and 3f have potential cytotoxic activities, especially on A549 cells with IC = 2.3 µM and 1.15 µM, respectively. Meanwhile, they recorded a minimal cytotoxic effect on WI-38 cells. Concerning the molecular mechanism of action, the present study showed the inhibitory effect of the six compounds against total EGFR. The most potent EGFR inhibitors were 3e and 3f with IC = 0.031 µM and 0.023 µM, respectively. The selectivity index of 3f for EGFR was 1.81 times more selective than that of lapatinib. In addition, 3e and 3f initiated cell cycle arrest at the G2/M and pre-G1 phases along with the downregulation of anti-apoptotic protein Bcl2 and the upregulation of pro-apoptotic proteins: p53, Bax, and caspases 3, 8, and 9. Further studies are recommended to evaluate animal models' promising anticancer activity and molecular mechanism of triazolo[3,4-a]isoquinoline derivatives 3e and 3f.

Adnane, F., S. M. A. Soliman, E. Elzayat, E. M. Abdelsalam, and H. M. Fahmy, "Evaluation of chlorophyll-loaded mesoporous silica nanoparticles for photodynamic therapy on cancer cell lines.", Lasers in medical science, vol. 39, issue 1, pp. 45, 2024 Jan 23. Abstract

Chlorophyll (Chl) is a promising natural photosensitizer (PS) in photodynamic treatment (PDT). Mesoporous silica nanoparticles (MSNs) were chosen to increase the effectiveness of PDT. This study aimed to evaluate the synergistic efficacy of chlorophyll-loaded mesoporous silica nanoparticles (Chl-MSNs) with photodynamic therapy (PDT) and to investigate their potential toxicity in HepG2, MDA-MB-231, and HSF cell lines. Chl-MSNs were prepared via the physical adsorption method. TEM, DLS, and zeta potential examined morphology, size, and surface characteristics. MSNs and Chl-MSNs were characterized using the same techniques. HPLC was used to assess the encapsulation efficiency. At pH 7.4, an in vitro release experiment of Chl-MSNs was performed. Chl, MSNs, and Chl-MSNs were applied to the three cell lines at different concentrations and subjected to red (650 nm) and blue (450-500 nm) lasers. MSNs and Chl-MSNs' sizes were 90.338 ± 38.49 nm and 123.84 ± 15.67 nm, respectively, as obtained by TEM; the hydrodynamic diameter for MSNs (93.69 ± 20.53 nm) and Chl-MSNs (212.95 ± 19.76 nm); and their zeta potential values are - 16.7 ± 2.19 mV and - 18.84 ± 1.40 mV. The encapsulation efficiency of Chl-MSNs was 70%. Chl-MSNs displayed no toxicity in dark conditions but showed excellent photostability under blue and red light exposure. Furthermore, using Chl over Chl-MSNs has a higher PDT efficiency than the tested cell lines. Chl-MSNs have the potential to be an effective delivery system. PDT proved to be an essential technique for cancer treatment. Blue laser is recommended over red laser with Chl and MSNs for destroying cancer cells.

Wafaa Mansour, M. K., S. A. Emad Elzayat, H. A. E. F. E. S. Dalia Mahmood, and S. S. Taghreed Hussein, "Therapeutic Role of Bone Marrow-Derived Mesenchymal Stem Cells in Controlling Prognosis of Hepatocellular Carcinoma in a Murine Model", Experimental and Clinical Transplantation, vol. 20, issue 1, pp. 62-68, 2022.
El-Zayat, E., and A. Rawi, S. and Gawish, "Hypogonadal dysfunction induced by aluminium intoxication in male rat and the protective role of antioxidants", J. Egy. Ger Soc. Zool, vol. 12, pp. 71-97, 1996. Abstract

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El-Shazly, M., and H. El-Zayat, E. and Hermersdoerfer, "Insecticidal activity, cytotoxicity and mutagenicity of ethanol extract of Nerium oleander leaves.", Ann. Appl. Biol., vol. 139, pp. 153-157., 2000. Abstract

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Soliman, M. H., M. A. Ragheb, E. M. Elzayat, M. S. Mohamed, N. El-Ekiaby, A. I. Abdelaziz, and A. - H. A. Abdel-Wahab, "MicroRNA-372-3p predicts response of TACE patients treated with doxorubicin and enhances chemosensitivity in hepatocellular carcinoma", Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), vol. 21, issue 2: Bentham Science Publishers, pp. 246-253, 2021. Abstract
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