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Muhammed A Saad,1,2 Noha M Eissa,2 Mohammed A Ahmed,3 Aliaa N ElMeshad,3,4 Götz Laible,5– 7 Ahmed S Attia,8 Medhat A Al-Ghobashy,9,10 Rania M Abdelsalam,1,2 Muhammad Y Al-Shorbagy1,11 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2School of Pharmacy, Newgiza University, Giza, Egypt; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 4Faculty of Nanotechnology for Postgraduate Studies, Cairo University, Giza, Egypt; 5AgResearch, Ruakura Research Centre, Hamilton, New Zealand; 6School of Medical Sciences, University of Auckland, Auckland, New Zealand; 7Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand; 8Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 9Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 10Bioanalysis Research Group, School of Pharmacy, Newgiza University, Giza, Egypt; 11Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman, United Arab EmiratesCorrespondence: Ahmed S Attia, Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt, Email ahmed.attia@pharma.cu.edu.egIntroduction: Rituximab (RTX) and recombinant human myelin basic protein (rhMBP) were proven to be effective in ameliorating the symptoms of multiple sclerosis (MS). In this study, a nanoformulation containing rhMBP with RTX on its surface (Nano-rhMBP-RTX) was prepared and investigated in comparison with other treatment groups to determine its potential neuro-protective effects on C57BL/6 mice after inducing experimental autoimmune encephalomyelitis (EAE).Methods: EAE was induced in the corresponding mice by injecting 100 μL of an emulsion containing complete Freund’s adjuvant (CFA) and myelin oligodendrocyte glycoprotein (MOG). The subjects were weighed, scored and subjected to behavioural tests. After reaching a clinical score of 3, various treatments were given to corresponding EAE-induced and non-induced groups including rhMBP, RTX, empty nanoparticle prepared by poly (lactide-co-glycolide) (PLGA) or the prepared nanoformulation (Nano-rhMBP-RTX). At the end of the study, biochemical parameters were also determined as interferon-γ (IFN-γ), myeloperoxidase (MPO), interleukin-10 (IL-10), interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-kB), brain derived neurotrophic factor (BDNF), 2’, 3’ cyclic nucleotide 3’ phosphodiesterase (CNP) and transforming growth factor beta (TGF-β) along with some histopathological analyses.Results: The results of the Nano-rhMBP-RTX group showed promising outcomes in terms of reducing the clinical scores, improving the behavioural responses associated with improved histopathological findings. Elevation in the levels of IL-4, CNP and TGF-β was also noticed along with marked decline in the levels of NF-kB and TNF-α.Conclusion: Nano-rhMBP-RTX treated group ameliorated the adverse effects induced in the EAE model. The effectiveness of this formulation was demonstrated by the normalization of EAE-induced behavioral changes and aberrant levels of specific biochemical markers as well as reduced damage of hippocampal tissues and retaining higher levels of myelination.Keywords: multiple sclerosis, experimental autoimmune encephalomyelitis, nanoparticle, rituximab, recombinant human myelin basic protein

Aya Ahmed Sebak,1 Iman Emam Omar Gomaa,2 Aliaa Nabil ElMeshad,3 Mahmoud Hussien Farag,1 Ulrike Breitinger,4 Hans-Georg Breitinger,4 Mahmoud Hashem AbdelKader5,6 1Pharmaceutical Technology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, Egypt; 2Biochemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 4Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, Egypt; 5National Institute of Laser Enhanced Sciences (NILES), Cairo University (CU), Giza, Egypt; 6European University in Egypt (EUE), New Administrative Capital, Cairo, EgyptCorrespondence: Aya Ahmed SebakFaculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, EgyptTel +20 1205727787Email aya.sebak@gmail.comIman Emam Omar GomaaBiochemistry Department Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, EgyptTel +20 1275146432Email gomaa.iman@gmail.comIntroduction: Nanoparticles (NPs), upon introduction to the biological systems, become wrapped by serum and cellular proteins constituting the protein corona (PC). This PC contributes largely to the NPs’ interaction with the biological systems and their subsequent functions. On the one hand, PC can decrease the efficiency of targeting by directing the NPs to the reticuloendothelial system (RES) or by masking the active targeting moieties and decreasing their ability to bind to their target receptors. On the other hand, some components of PC have offered hopes for achieving endogenous targeting.Methods: In this study, we aimed at the investigation of the role of the PC in determining the behavior of cRGDyk peptide-unconjugated and -conjugated NPs (uNPs and cNPs) exhibiting different physicochemical properties and their interaction with melanoma on in vitro and in vivo levels. Mathematical modeling has been utilized to understand the kinetics of the interaction of NPs with the tumor cells and different organs, respectively.Results: Endocytosis and exocytosis were reported to occur simultaneously for the utilized NPs. The balance was largely dependent on the NPs’ physicochemical properties and the role of the PC. In addition, distinct proteins present in the PC (illustrated in the results of the PC analysis in part I) have also determined the patterns of the NPs’ distribution in different organs and tissues of the vascular system, the RES system and the target tumot tissue. Vitronectin (VN) was found to mediate higher accumulation in integrin receptor-expressing melanoma cells, while complement 3 protein (C3) and clusterin (CLU), as an opsonin and dysopsonin, respectively, regulated the balance between the RES uptake and blood circulation.Discussion: PC, if properly modulated by tuning NPs’ physicochemical properties, can serve as a potential venue for optimum utilization of NPs in cancer therapy.Keywords: Protein corona, endogenous targeting, melanoma, endocytosis, exocytosis, biodistribution, pharmacokinetics

Aya Ahmed Sebak,1 Iman Emam Omar Gomaa,2 Aliaa Nabil ElMeshad,3 Mahmoud Hussien Farag,1 Ulrike Breitinger,4 Hans-Georg Breitinger,4 Mahmoud Hashem AbdelKader5,6 1Pharmaceutical Technology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, Egypt; 2Biochemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Giza, Egypt; 4Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, Egypt; 5National Institute of Laser Enhanced Sciences (NILES), Cairo University (CU), Giza, Egypt; 6European University in Egypt (EUE), New Administrative Capital, Cairo, EgyptCorrespondence: Aya Ahmed SebakFaculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, EgyptTel +20 1205727787Email aya.sebak@gmail.comIman Emam Omar GomaaBiochemistry Department Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, EgyptTel +20 1275146432Email gomaa.iman@gmail.comIntroduction: Protein corona (PC) deposition on nanoparticles (NPs) in biological systems contributes to a great extent to NPs’ fates; their targeting potential, the interaction with different biological systems and the subsequent functions. PC – when properly tuned – can serve as a potential avenue for optimization of NPs’ use in cancer therapy.Methods: Poly-lactic co-glycolic acid (PLGA)-based NPs exhibiting different physicochemical properties were fabricated and characterized. The PC makeup of these NPs were qualitatively and quantitatively analyzed by Western blot and Bradford assay, respectively. The effect of PC on the release of NPs’ cargos and the intracellular uptake into B16F10 melanoma cells has been studied.Results: The composition of NPs (polymeric PLGA NPs vs lipid-polymer hybrid NPs) and the conjugation of an active targeting ligand (cRGDyk peptide) represented the major determinants of the PC makeup of NPs. The in vitro release of the loaded cargos from the NPs depended on the PC and the presence of serum proteins in the release medium. Higher cumulative release has been recorded in the presence of proteins in the case of peptide conjugated NPs, cNPs, while the unconjugated formulations, uNPs, showed an opposite pattern. NPs intracellular uptake studies revealed important roles of distinct serum and cellular proteins on the extent of NPs’ accumulation in melanoma cells. For example, the abundance of vitronectin (VN) protein from serum has been positively related to the intracellular accumulation of the NPs.Conclusion: Careful engineering of nanocarriers can modulate the recruitment of some proteins suggesting a potential use for achieving endogenous targeting to overcome the current limitations of targeted delivery of chemotherapeutic agents.Keywords: nanoparticles, active targeting, passive targeting, endogenous targeting, melanoma, protein corona, intracellular uptake

Shaimaa Ali Ali Radwan,1 Walaa H El-Maadawy,2 Carol Yousry,1 Aliaa Nabil ElMeshad,1 Raguia Aly Shoukri1 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmacology, Theodor Bilharz Research Institute, Giza 12411, EgyptCorrespondence: Aliaa Nabil ElMeshadDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr Al Aini Street, Cairo 11562, EgyptTel +201000101551Email aliaa.elmeshad@pharma.cu.edu.egPurpose: Zein/phospholipid composite nanoparticles (CNPs) were developed as a delivery platform for gallic acid (GA), a polyphenolic compound with reported preclinical antifibrotic activities. However, the therapeutic applicability of GA is hampered owing to its low bioavailability and rapid clearance. Accordingly, we developed GA-loaded CNPs. The effect of their size, surface charge and targeting strategies was investigated and optimized, with the aim of enhancing their ability to deliver GA to the activated hepatic stellate cells (aHSCs) in order to suppress hepatic fibrosis progression.Methods: Different CNP systems were prepared and characterized with regard to their particle size, zeta potential, and GA entrapment efficiency (EE%). Also, they were statistically optimized via response surface methodology. The optimized systems were investigated with regard to their in vitro GA release, in vitro efficacy on aHSCs, and in vivo biodistribution in healthy rats.Results: The GA-loaded cationic CNPs coupled with vitamin A (GA-CACNP/VA; 192 nm) showed high GA EE% (60% w/w), highest cellular internalization via active targeting, and more selective hepatic distribution, relative to free GA solution, GA-loaded anionic, and GA-loaded cationic systems. Furthermore, GA-CACNP/VA markedly triggered the apoptosis of aHSCs, repressed collagen deposition, and inhibited HSCs’ activation to a lesser extent.Conclusion: The GA-CACNP/VA was shown to be a promising candidate for specific and controlled delivery of GA to aHSCs, which may provide an effective antifibrotic therapeutic approach.Keywords: zein, phospholipids, gallic acid, hepatic fibrosis, hepatic stellate cells, vitamin A

Abstract Background Hepatic cancer endures a major health scourge as the consequence of a high incidence of > 1 million cases by 2025. Plant-based products are typically effective in ameliorating health conditions. Pomegranate peel extract (PE) with its high polyphenolic content has anticancer effects against different types of cancer. Herein, we aimed to maximize the PE chemotherapeutic efficacy by loading it in a suitable delivery system to overcome the limitations of PE, to control its release and to achieve liver targeting. Method A nanoprecipitation procedure was adopted to incorporate PE into biodegradable and biocompatible natural polymeric zein (ZN)-based nanoparticles (NPs) (PE-ZN NPs). A full factorial design (22 × 31) was developed to study the effects of the formulation variables, namely pH of dispersion, PE-to-ZN ratio and surfactant concentration. Results The optimization revealed a surfactant-free stable PE-ZN NPs formula with a small particle size of 99.5 ± 6.43 nm, high PE encapsulation efficiency % of 99.31% ± 3.64 (w/w) and controlled release of PE over 24 h. Conclusion Moreover, the cytotoxicity of the optimum formula against hepatic cancer HepG2 cell lines was assessed and attained about a 2.5-fold reduction in the inhibitory concentration (IC50) values compared to the free PE affording a promising green platform to combat hepatic cancer. Graphical abstract

Manal Fouad Ismail,1 Aliaa Nabil ElMeshad,2 Neveen Abdel-Hameed Salem31Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Department of Narcotics and Ergogenic Aids and Poisons, National Research Center, Giza, EgyptBackground: To sustain the effect of rivastigmine, a hydrophilic cholinesterase inhibitor, nanobased formulations were prepared. The efficacy of the prepared rivastigmine liposomes (RLs) in comparison to rivastigmine solution (RS) was assessed in an aluminium chloride (AlCl3)-induced Alzheimer’s model.Methods: Liposomes were prepared by lipid hydration (F1) and heating (F2) methods. Rats were treated with either RS or RLs (1 mg/kg/day) concomitantly with AlCl3 (50 mg/kg/day).Results: The study showed that the F1 method produced smaller liposomes (67.51 ± 14.2 nm) than F2 (528.7 ± 15.5 nm), but both entrapped the same amount of the drug (92.1% ± 1.4%). After 6 hours, 74.2% ± 1.5% and 60.8% ± 2.3% of rivastigmine were released from F1 and F2, respectively. Both RLs and RS improved the deterioration of spatial memory induced by AlCl3, with RLs having a superior effect. Further biochemical measurements proved that RS and RLs were able to lower plasma C-reactive protein, homocysteine and asymmetric dimethylarginine levels. RS significantly attenuated acetylcholinesterase (AChE) activity, whereas Na+/K+-adenosine triphosphatase (ATPase) activity was enhanced compared to the AlCl3-treated animals; however, RLs succeeded in normalization of AChE and Na+/K+ ATPase activities. Gene-expression profile showed that cotreatment with RS to AlCl3-treated rats succeeded in exerting significant decreases in BACE1, AChE, and IL1B gene expression. Normalization of the expression of the aforementioned genes was achieved by coadministration of RLs to AlCl3-treated rats. The profound therapeutic effect of RLs over RS was evidenced by nearly preventing amyloid plaque formation, as shown in the histopathological examination of rat brain.Conclusion: RLs could be a potential drug-delivery system for ameliorating Alzheimer's disease.Keywords: rivastigmine, Alzheimer’s disease, liposomes, rats, gene expression

This study aims to know the level of student self-efficacy, the level of subject mastery and the relationship between student self-efficacy and mastery of online Arabic lessons. This study used correlation research with a total of 154 respondents in 5 (five) Madrasah Aliyah Palangka Raya. Methods of data collection used questionnaires and documents. The results showed that: The average level of self-efficacy of students in learning Arabic online was 3.1911 which means the high category. The level of mastery of Arabic lessons in online learning is 7.2468, which means the medium category. There is a positive relationship between students' self-efficacy and mastery of online Arabic lessons which is classified as good with a sig p = 0.000 0.05. Self-efficacy will have a good influence on the results of mastery of lessons conducted online. الغرض من هذه الدراسة هو تحديد مدى فعالية إتقان الطلاب للموضوع ومدى ارتباطه بكفاءتهم الذاتية عند تعلم اللغة العربية عبر الإنترنت. لتحقيق هذا الهدف ، تم إجراء بحث كمي باستخدام طريقة مسح شملت 154 مستجيبًا من خمس مدارس عالية بالانجكا رايا وباستخدام استبيان كأداة لجمع البيانات. أظهرت النتائج أن متوسط مستوى الكفاءة الذاتية للطلاب في تعلم اللغة العربية على الإنترنت كان مرتفعًا جدًا ، وهو 3.1911. يتم تصنيف الطلاب أيضًا على أنهم يتمتعون بمستوى متوسط في إتقان اللغة العربية ، وهو 7.2468. بالإضافة إلى ذلك ، وجدت الدراسة أيضًا علاقة إيجابية بين الكفاءة الذاتية للطلاب وإتقان دروس اللغة العربية عبر الإنترنت والتي تم تصنيفها على أنها جيدة مع قيمة دلالة وجدت p أقل من 0.05. يمكن أن نستنتج أن الكفاءة الذاتية يمكن أن يكون لها تأثير إيجابي على نتائج التعلم عبر الإنترنت.

Obesity has been associated with the occurrence and prevalence of various chronic metabolic diseases. The management of obesity has evolved to focus not only on reducing weight, but also on preventing obesity-related complications. Studies have shown that bioactive components in natural products like white kidney bean extract (WKBE), propolis ethanolic extract (PEE), and chromium picolinate (CrPi3) showed anti-obesity properties. However, no studies have examined the outcomes of combining any of these nutraceutical supplements. We compared the effects of HFD supplemented with WKBE, WKBE+PEE, or WKBE+PEE+CrPi3 against control and obese groups using Sprague-Dawley rats fed a 45% high-fat diet as an in vivo model. Nutritional parameters, biochemical parameters, and biomarkers of cardiovascular disease, liver function, kidney function, and gut health were among the comparable effects. Our findings showed that combining the three nutraceutical supplements had a synergetic effect on reducing weight gain, food utilization rate, abdominal fat, serum lipids, arterial and hepatic lipids, risk of cardiovascular disease, and blood glucose level, in addition to improving renal function and gut microbiota. We attributed these effects to the α-amylase inhibitor action of WKBE, flavonoids, and polyphenol content of PEE, which were potentiated with CrPi3 resulting in a further reduction or normalization of certain parameters.

The current study aimed to fabricate curcumin-loaded bilosomal hydrogel for topical wound healing purposes, hence alleviating the poor aqueous solubility and low oral bioavailability of curcumin. Bilosomes were fabricated via the thin film hydration technique using cholesterol, Span® 60, and two different types of bile salts (sodium deoxycholate or sodium cholate). Bilosomes were verified for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%), and in vitro drug release besides their morphological features. The optimum formulation was composed of cholesterol/Span® 60 (molar ratio 1:10 w/w) and 5 mg of sodium deoxycholate. This optimum formulation was composed of a PS of 246.25 ± 11.85 nm, PDI of 0.339 ± 0.030, ZP of −36.75 ± 0.14 mv, EE% of 93.32% ± 0.40, and the highest percent of drug released over three days (96.23% ± 0.02). The optimum bilosomal formulation was loaded into alginate dialdehyde/chitosan hydrogel cross-linked with calcium chloride. The loaded hydrogel was tested for its water uptake capacity, in vitro drug release, and in vivo studies on male Albino rats. The results showed that the loaded hydrogel possessed a high-water uptake percent at the four-week time point (729.50% ± 43.13) before it started to disintegrate gradually; in addition, it showed sustained drug release for five days (≈100%). In vivo animal testing and histopathological studies supported the superiority of the curcumin-loaded bilosomal hydrogel in wound healing compared to the curcumin dispersion and plain hydrogel, where there was a complete wound closure attained after the three-week period with a proper healing mechanism. Finally, it was concluded that curcumin-loaded bilosomal hydrogel offered a robust, efficient, and user-friendly dosage form for wound healing.

Curcumin or turmeric is the active constituent of Curcuma longa L. It has marvelous medicinal applications in many diseases. When the skin integrity is compromised due to either acute or chronic wounds, the body initiates several steps leading to tissue healing and skin barrier function restoration. Curcumin has very strong antibacterial and antifungal activities with powerful wound healing ability owing to its antioxidant activity. Nevertheless, its poor oral bioavailability, low water solubility and rapid metabolism limit its medical use. Tailoring suitable drug delivery systems for carrying curcumin improves its pharmaceutical and pharmacological effects. This review summarizes the most recent reported curcumin-loaded delivery systems for wound healing purposes, chiefly hydrogels, films, wafers, and sponges. In addition, curcumin nanoformulations such as nanohydrogels, nanoparticles and nanofibers are also presented, which offer better solubility, bioavailability, and sustained release to augment curcumin wound healing effects through stimulating the different healing phases by the aid of the small carrier.

Obesity has been associated with the occurrence and prevalence of various chronic metabolic diseases. The management of obesity has evolved to focus not only on reducing weight, but also on preventing obesity-related complications. Studies have shown that bioactive components in natural products like white kidney bean extract (WKBE), propolis ethanolic extract (PEE), and chromium picolinate (CrPi3) showed anti-obesity properties. However, no studies have examined the outcomes of combining any of these nutraceutical supplements. We compared the effects of HFD supplemented with WKBE, WKBE+PEE, or WKBE+PEE+CrPi3 against control and obese groups using Sprague-Dawley rats fed a 45% high-fat diet as an in vivo model. Nutritional parameters, biochemical parameters, and biomarkers of cardiovascular disease, liver function, kidney function, and gut health were among the comparable effects. Our findings showed that combining the three nutraceutical supplements had a synergetic effect on reducing weight gain, food utilization rate, abdominal fat, serum lipids, arterial and hepatic lipids, risk of cardiovascular disease, and blood glucose level, in addition to improving renal function and gut microbiota. We attributed these effects to the α-amylase inhibitor action of WKBE, flavonoids, and polyphenol content of PEE, which were potentiated with CrPi3 resulting in a further reduction or normalization of certain parameters. [ABSTRACT FROM AUTHOR]

The objective of the present research is to propose chitosan as a nanocarrier for caffeine—a commonly used drug in combating cellulite. Being a hydrophilic drug, caffeine suffers from insufficient topical penetration upon application on the skin. Chitosan nanoparticles loaded with caffeine were prepared via the ionic gelation technique and optimized according to a Box–Behnken design. The effect of (A) chitosan concentration, (B) chitosan solution pH, and (C) chitosan to sodium tripolyphosphate mass ratio on (Y1) entrapment efficiency percent, (Y2) particle size, (Y3) polydispersity index, and (Y4) zeta potential were studied. Subsequently, the desired constraints on responses were applied, and validation of the optimization procedure was confirmed by the parameters exhibited by the optimal formulation. A caffeine entrapment efficiency percent of 17.25 ± 1.48%, a particle size of 173.03 ± 4.32 nm, a polydispersity index of 0.278 ± 0.01, and a surface charge of 41.7 ± 3.0 mV were attained. Microscopical evaluation using transmission electron microscope revealed a typical spherical nature of the nanoparticles arranged in a network with a further confirmation of the formation of particles in the nano range. The results proved the successful implementation of the Box–Behnken design for optimization of chitosan-based nanoparticles in the field of advanced polymeric systems for pharmaceutical and cosmeceutical applications.