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Sammar Fathy Elhabal,1 Saeed AS Al-Zuhairy,2 Mohamed El-Nabarawi,3 Mohamed Fathi Mohamed Elrefai,4,5 Mai S Shoela,6 Sandra Hababeh,7 Jakline Nelson,8 Mohamed A Abdel Khalek,9 Marwa Fady,10,11 Nahla A Elzohairy,11,12 Mariam E Amin,13 Gehad M Khamis,6 Amira Rizk,14 Sara Mohamed Ahmed,15 Ahmed A El-Rashedy,16 Mohamed Mohany,17 Abdulaziz S Al-Roujayee,18 Ahmed Mohsen Faheem,19 Amr Amin20 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, Egypt; 2Department of Pharmacy, Kut University College, Kut, Wasit, Iraq; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 4Department of Anatomy, physiology and Biochemistry, Faculty of Medicine, the Hashemite University, Zarqa, Jordan; 5Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 7Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 8Department of Microbiology and Immunology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; 9Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt; 10Zagazig University Hospitals, Infection Control Unit, Zagazig, 44519, Egypt; 11Modern University for Technology & Information, Department of Microbiology and Immunology, Pharmacy College., Cairo Governorat, Egypt; 12Air Force Specialized Hospital, Cairo, Egypt; 13Microbiology and Immunology Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt; 14Food Science and technology, Department Faculty of Agricultural, Tanta University, Tanta, Egypt; 15Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, 12585, Egypt; 16Chemistry of Natural and Microbial Products Department, National Research Center (NRC), Giza, Egypt; 17Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 18Department of Dermatology and Venereology, College of Medicine, Al Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia; 19Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 20College of Medicine, Sharjah University, Sharjah, United Arab EmiratesCorrespondence: Sammar Fathy Elhabal; Amr Amin, Email sammar_fathy2007@yahoo.com, sammar.fathy@pharm.mti.edu.eg; a.amin@sharjah.ac.aeBackground: Diabetic foot ulcers present a formidable challenge due to colonization by biofilm-forming microorganisms, heightened oxidative stress, and continuous wound maceration caused by excessive exudation.Methods: To address these issues, we developed a robust, stretchable, electro-conductive, self-healing, antioxidant, and antibiofilm hydrogel. This hydrogel was synthesized through the crosslinking of polyvinyl alcohol (PVA) and chitosan (CH) with boric acid. To enhance its antimicrobial efficacy, graphene oxide (GO), produced via electrochemical exfoliation in a zinc ion-based electrolyte medium, was incorporated. For optimal antibiofilm performance, GO was functionalized with cranberry (CR) phenolic extracts, forming a graphene oxide-cranberry nanohybrid (GO-CR).Results: The incorporation of GO-CR into the hydrogel significantly improved its stretchability (280% for PVA/CH/GO-CR compared to 200% for PVA/CH). Additionally, the hydrogel demonstrated efficient photothermal conversion under near-infrared (NIR) light, enabling dynamic exudate removal, which is expected to minimize retained exudate between the wound and the dressing, reducing the risk of wound maceration. The hydrogel effectively reduced levels of lipopolysaccharide (LPS)-induced skin inflammation markers, significantly lowering the expression of NLRP3, TNF-α, IL-6, and IL-1β by 39.2%, 31.9%, 41%, and 52.3%, respectively. Histopathological and immunohistochemical analyses further confirmed reduced inflammation and enhanced wound healing.Conclusion: The PVA/CH/GO-CR hydrogel exhibits multifunctional properties that enhance wound healing ulcers. Its superior mechanical, antibacterial, and anti-inflammatory properties and ability to promote angiogenesis make it a promising candidate for effective wound management in diabetic patients. Keywords: antibiofilm, cranberry extract, electro conductive hydrogel, graphene oxide, nanocomposite, photothermal conversion, self-healing, wound healing

Sammar Fathy Elhabal,1 Nashwa Abdelaal,2 Saeed Abdul Kareem Saeed Al-Zuhairy,3 Mohamed Fathi Mohamed Elrefai,4,5 Ahmed Mohsen Elsaid Hamdan,6 Mohamed Mansour Khalifa,7 Sandra Hababeh,8 Mohammad Ahmad Khasawneh,9 Gehad M Khamis,10 Jakline Nelson,11 Passant M Mohie,10 Rania A Gad,12 Amira Rizk,13 Soad L Kabil,14 Mohamed Kandeel El-Ashery,15,16 Bhaskara R Jasti,17 Nahla A Elzohairy,18,19 Tayseer Elnawawy,20 Fatma E Hassan,21,22 Mohamed A El- Nabarawi23 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, Egypt; 2Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA; 3Department of Pharmacy, Kut University College, Kut, Wasit, Iraq; 4Department of Anatomy, Histology, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan; 5Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; 7Department of Human Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt; 8Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 9Department of Chemistry, College of Science U.A.E. University, Al-Ain, United Arab Emirates; 10Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 11Department of Microbiology and Immunology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; 12Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; 13Food Science and Technology Department, Faculty of Agricultural, Tanta University, Tanta, Egypt; 14Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 15Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 16Medicinal Chemistry Department, Faculty of Pharmacy, King Salman International University, Ras-Sedr, South Sinai, Egypt; 17Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA, USA; 18Air Force Specialized Hospital, Cairo, Egypt; 19Department of Microbiology and Immunology, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, Egypt; 20Department of Pharmaceutics, Egyptian Drug Authority, Cairo, Egypt; 21Medical Physiology Department, Faculty of Medicine, Cairo University, Giza, Egypt; 22General Medicine Practice Program, Department of Physiology, Batterjee Medical College, Jeddah, Saudi Arabia; 23Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, EgyptCorrespondence: Sammar Fathy Elhabal, Email Sammar.Fathy@pharm.mti.edu.eg; sammar_fathy2007@yahoo.com; Mohamed A El- Nabarawi, Email mohamed.elnabarawi@pharm.cu.edu.egBackground: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel.Method and Results: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1β, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models.Conclusion: These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing. Keywords: wound healing, antimicrobial, antioxidant, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, chitosan, wound concentration, wound incision

Sammar Fathy Elhabal,1 Nashwa Abdelaal,2 Saeed AS Al-Zuhairy,3 Mohamed Fathi Mohamed Elrefai,4,5 Mohamed Mansour Khalifa,6 Mohammad Ahmad Khasawneh,7 Ahmed Mohsen Elsaid Hamdan,8 Passant M Mohie,9 Rania A Gad,10 Soad L Kabil,11 Mohamed Kandeel El-Ashery,12,13 Bhaskara R Jasti,14 Nahla A Elzohairy,15,16 Nehal Elfar,17 Tayseer Elnawawy,18 Fatma E Hassan,19,20 Mohamed Ahmed El-Nabarawi21 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, Egypt; 2Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA; 3Department of Pharmacy, Kut University College, Kut, Wasit, Iraq; 4Department of Anatomy, Histology, Physiology, and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan; 5Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Department of Human Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt; 7Department of Chemistry, College of Science, U.A.E. University, Al-Ain, United Arab Emirates; 8Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; 9Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 10Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; 11Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 12Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 13Medicinal Chemistry Department, Faculty of Pharmacy, King Salman International University, Ras-Sedr, South Sinai, Egypt; 14Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy & Health Sciences, University of the Pacific, Stockton, CA, USA; 15Air Force Specialized Hospital, Cairo, Egypt; 16Department of Microbiology and Immunology, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, Egypt; 17Department of Pharmaceutical Technology, Faculty of Pharmacy, Horus University, New Demiette, Egypt; 18Department of Pharmaceutics, Egyptian Drug Authority, Cairo, Egypt; 19Medical Physiology Department, Kasr Alainy, Faculty of Medicine, Cairo University, Giza, Egypt; 20General Medicine Practice Program, Department of Physiology, Batterjee Medical College, Jeddah, Saudi Arabia; 21Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, EgyptCorrespondence: Mohammad Ahmad Khasawneh, Email mohammad.khasawneh@uaeu.ac.aePurpose: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential.Methods: Firstly, we developed a niosomal drug delivery system based on ceramide IIIB to form Cerosomes. Cerosomes were prepared from a mixture of Ceramide, hyaluronic acid, and edge activator using a thin-film hydration technique. To co-deliver CsA and DTH topically for the treatment of psoriasis. These two hydrophobic drugs encapsulated into our synthesized positively charged particle cerosomes.Results: Cerosomes had an average particle size of (222.36 nm± 0.36), polydispersity index of (0.415± 0.04), Entrapment Efficiency of (96.91%± 0.56), and zeta potential of (29.36± 0.38mV) for selected formula. In vitro, In silico, in vivo, permeation, and histopathology experiments have shown that cerosomes enhanced the skin penetration of both hydrophobic drugs by 66.7% compared to the CsA/DTH solution. Imiquimod (IMQ) induced psoriatic mice model was topically treated with our CsA/DTH cerosomes. We found that our formulation enhances the skin penetration of both drugs and reduces psoriasis area and severity index (PASI score) by 2.73 times and 42.85%, respectively, compared to the CsA/DTH solution. Moreover, it reduces the levels of proinflammatory cytokines, TNF-α, IL-10, and IL-6 compared to CsA/DTH solution administration.Conclusion: The Cerosomes nano-vesicle-containing CsA/DTH represents a more promising topical treatment for psoriasis, giving new hope to individuals with psoriasis, compared to commercial and other conventional alternatives. Keywords: biopharmaceutics classification system class II, BCS II, niosomes based on ceramide IIIB, cerosomes, psoriasis, psoriasis area and severity index, PASI score, imiquimod, IMQ, proinflammatory cytokines, niosomes

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (-18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the in-vivo study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ's antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets.

The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans , Fusarium, and Aspergillus flavus , and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co -loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo . The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections., Competing Interests: The authors wish to declare no interest is involved in this publication., (© 2023 The Authors.)

Several food-poisoning outbreaks have been attributed to Clostridium perfringens ( C. perfringens ) worldwide. Despite that, this crisis was discussed in a few studies, and additional studies are urgently needed in this field. Therefore, we sought to highlight the prevalence, antimicrobial resistance, toxin profiles, and toxinotypes of C. perfringens isolates. In this study, 50 C. perfringens isolates obtained from 450 different animal origin samples (beef, chicken meat, and raw milk) were identified by phenotypic and genotypic methods. The antimicrobial susceptibility results were surprising, as most of the isolates (74%) showed multidrug-resistant (MDR) patterns. The phenotypic resistance to tetracycline, lincomycin, enrofloxacin, cefoxitin/ampicillin, and erythromycin was confirmed by the PCR detections of tet , lnu , qnr , bla , and erm (B) genes, respectively. In contrast to the toxinotypes C and E, toxinotype A prevailed (54%) among our isolates. Additionally, we found that the genes for C. perfringens enterotoxin ( cpe ) and C. perfringens beta2 toxin ( cpb 2) were distributed among the tested isolates with high prevalence rates (70 and 64%, respectively). Our findings confirmed that the C. perfringens foodborne crisis has been worsened by the evolution of MDR strains, which became the prominent phenotypes. Furthermore, we were not able to obtain a fixed association between the toxinotypes and antimicrobial resistance patterns.