Anti-leishmanial activities of Olea europaea subsp. laperrinei extracts.

Leishmaniasis is an infectious disease that is often fatal in affected patients and represents a major public health problem. At present, no vaccine is available, and the drug treatments used are costly, long, and have numerous side effects, they also present variable effectiveness, frequent relapses, and a more and more marked resistance towards the parasites. Thus, new therapeutic strategies are urgently needed, and they are mainly based on the research of active natural products. The objective of our study is the chemical characterization and the quantification of the polyphenol contents contained in the EAF and EAT extracts of the Laperrine olive tree and the evaluation of their antileishmania effect against Leishmania infantum. The quantification of polyphenols, flavonoids and total tannins shows a higher content in the leaf extract. We find respectively 776.76±30.64 mg gallic acid equivalent/g DR; 114.35±14.12 mg quercetin equivalent/g DR and 214.89±.17 mg tannic acid equivalent/g DR.The chemical characterization of Olea europaea subsp. laperrinei extracts show the presence of numerous antileishmanial biomolecules such as oleuropein, hydroxytyrosol, rutin, gallic acid, cafeic acid, rosmarinic acid, and quercetin.In this context, we are testing the in vitro leishmanicidal effect of Laperrine olive tree extracts. The results obtained are promising and highlight the effectiveness of the tested extracts against the promastigote form of Leishmania infantum. Indeed, the LD50 is obtained with the leaf extract at a concentration of 7.52±2.71 µl/ml.

Astaxanthin: A Marine Drug That Ameliorates Cerebrovascular-Damage-Associated Alzheimer's Disease in a Zebrafish Model via the Inhibition of Matrix Metalloprotease-13.

Alzheimer's disease (AD) is a major type of dementia disorder. Common cognitive changes occur as a result of cerebrovascular damage (CVD) via the disruption of matrix metalloproteinase-13 (MMP-13). In diabetic cases, the progress of vascular dementia is faster and the AD rate is higher. Patients with type 2 diabetes are known to have a higher risk of the factor for AD progression. Hence, this study is designed to investigate the role of astaxanthin (AST) in CVD-associated AD in zebrafish via the inhibition of MMP-13 activity. CVD was developed through the intraperitoneal and intracerebral injection of streptozotocin (STZ). The AST (10 and 20 mg/L), donepezil (1 mg/L), and MMP-13 inhibitor (i.e., CL-82198; 10 µM) were exposed for 21 consecutive days in CVD animals. The cognitive changes in zebrafish were evaluated through light and dark chamber tests, a color recognition test, and a T-maze test. The biomarkers of AD pathology were assessed via the estimation of the cerebral extravasation of Evans blue, tissue nitrite, amyloid beta-peptide aggregation, MMP-13 activity, and acetylcholinesterase activity. The results revealed that exposure to AST leads to ameliorative behavioral and biochemical changes. Hence, AST can be used for the management of AD due to its multi-targeted actions, including MMP-13 inhibition.

Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells.

Accumulating evidence indicates that statins reduce the risk of different cancers and inhibit the proliferation of liver cancer cells. This study aims to explore whether the electrostatic conjugation of optimized fluvastatin (FLV) to human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) would enhance the anti-proliferative activity against HepG2 cells. FLV-TAT conjugation was optimized to achieve the lowest size with highest zeta potential. Nine formulae were constructed, using a factorial design with three factors-FLV concentration, TAT concentration, and pH of the medium-while the responses were zeta potential and size. The optimized formula showed a particle size of 199.24 nm and 29.14 mV zeta potential. Data indicates that conjugation of FLV to TAT (optimized formula) significantly enhances anti-proliferative activity and uptake by HepG2 cells when compared to raw FLV. Flow cytometry showed significant accumulation of cells in the pre-G phase, which highlights higher apoptotic activity. Annexin V staining indicated a significant increase in total cell death in early and late apoptosis. This was confirmed by significantly elevated caspase 3 in cells exposed to FLV-TAT preparation. In conclusion, the FLV-TAT optimized formula exhibited improved anti-proliferative action against HepG2. This is partially attributed to the enhanced apoptotic effects and cellular uptake of FLV.

Physicochemical, pharmacokinetics, and histological evaluation of new naproxen-quercetin co-lyophilizate to diminish drug-induced gastric irritations in rats.

Quercetin (QUE) is a flavonoid found in several plants and commonly distributed in edible vegetables and fruits. To evaluate the effect of co-lyophilization of naproxen (NPX) with QUE at different weight ratios on physicochemical characteristics induced gastric irritation, and drug pharmacokinetics. NPX binary systems with QUE in different weight ratios were prepared by freeze-drying alkalinized solutions, and were characterized in terms of physicochemical properties as well as NPX dissolution rate in acidic pH. NPX-induced gastric inflammation studies were carried out in rats for 7 days. The pharmacokinetics of the two formulations were assessed to evaluate the bioavailability of NPX-QUE 1:2 co-lyophilizate. Westar rats were administered oral doses equivalent to 40 mg kg-1 of NPX and blood samples were taken from the retro-orbital vein of rats at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 12.0, and 24.0 h post dosing. Co-lyophilization of NPX with QUE enhanced drug dissolution rate in the acidic medium, which was correlated with an increased QUE weight ratio in the co-lyophilizates. Rat stomachs from group V (NPX-QUE 1:2 co-lyophilizate) showed non-significant changes, and biopsies from this group showed no significant leukocyte infiltration and edema in the mucosa. The bioavailability of NPX-QUE 1: 2 co-lyophilizate was similar to the control sample. NPX-QUE 1: 2 co-lyophilizate could be an alternative to NPX in the treatment of arthritis as it minimizes the potential for gastric irritation and enhances safety while retaining the same efficacy and bioavailability.

Formulation and evaluation of docetaxel nanosuspensions: In-vitro evaluation and cytotoxicity.

OBJECTIVE: The aim of the present study was to formulate the anticancer drug; docetaxel (DOX) as nanoparticles to enhance its biological activity. METHODOLOGY: Solvent precipitation method was used to prepare DOX-loaded nanoparticles and was stabilized by different concentrations of hydroxypropyl methylcellulose (HPMC, E5) and sodium deoxycholate (SDC). RESULTS: The results showed that the particle size of the prepared DOX nanoparticles stabilized by SDC was small in comparison to those stabilized by the corresponding HPMC concentrations. The smallest particle size (83.97 nm) was obtained by using SDC as stabilizer at 5% level with zeta potential of -13.6 mV. It was concluded that increasing the stabilizer concentration resulted in increase in both initial and overall cumulative drug release. The release rate in case of nanoparticles stabilized by 5% SDC was 33% and 87% after 1 and 24 h respectively. The results showed that a significant reduction in the viability of FRO cells was observed at all tested time intervals in case of nanoparticles stabilized by 5% SDC at concentrations of 100 and 1000 µM/ml. In contrast, no signs of cytotoxicity was observed for nanoparticles stabilized by 5% HPMC at 10 and 100 µM/ml concentrations.

Development of Domperidone Solid Lipid Nanoparticles: In Vitro and In Vivo Characterization.

Domperidone (DOP) is extensively applied orally in the management of nausea and vomiting. Upon oral administration, its bioavailability is very poor due to its poor solubility in alkaline media. Therefore, the aim of this work was to investigate DOP-loaded solid lipid nanoparticles (DOP-SLNs) in order to sustain its release pattern and to enhance oral bioavailability. DOP-SLNs were prepared using four different lipids. Prepared DOP-SLNs were characterized for "polydispersity index (PDI), particle size, zeta potential, % entrapment efficiency (% EE), and drug release behavior." Differential scanning calorimetry (DSC) study was carried out to illustrate the physical form of DOP and excipients. The morphology of DOP-SLNs was confirmed by scanning electron microscopy (SEM). Pharmacokinetic study on optimized DOP-SLN in comparison to tablet was performed in rats. The "particle size, PDI, zeta potential, and % EE" of optimized formulation (F5) were recorded as 201.4 nm, 0.071, - 6.2 mV, and 66.3%, respectively. DSC thermograms suggested amorphous state of DOP in various SLNs. Surface morphology of SLNs using SEM suggested spherical shape of the nanoparticles within nanometer size range. In vitro release studies confirmed that all SLN formulations possessed a sustained release over a period of 12 h (51.3% from optimized formulation) in comparison with immediate release from conventional tablets (100% after 90 min). Pharmacokinetic study showed significant enhancement in oral absorption of DOP from optimized SLN in comparison with DOP tablet. The enhancement in relative bioavailability of DOP from optimized SLN was 2.62-fold in comparison with DOP tablet.

Propafenone HCl fast dissolving tablets containing subliming agent prepared by direct compression method.

Propafenone HCl (PPH), an antiarrhythmic drug, has a bitter taste, short half-life, delayed drug dissolution and side effects. Thus, the purpose of this work is to develop orally fast dissolving tablets (OFDTs) containing PPH to provide a rapid drug dissolution and subsequently give rapid onset of action of PPH as an antiarrhythmic drug. Moreover, OFDTs of PPH reduce its side effects and improve its bioavailability. Propafenone HCl (PPH), an antiarrhythmic drug, has a bitter taste, short half-life, delayed drug dissolution and side effects. Direct compression method was used for the preparation of 15 formulations OFDTs containing PPH using directly compressible excipients, subliming agent and superdisintegrants. The prepared tablets were undergone physical characterization, in vitro dissolution and stability studies. All pre- and post-compression tests met the pharmacopoeia specifications. In vitro dissolution of the prepared PPH OFDTs exhibited high dissolution rate than compared to the marketed tablets. It was found that the tablets prepared by using the higher concentration of crospovidone were found to dissolute the drug at a faster rate when compared to other concentrations. A formula containing croscarmellose sodium showed the higher present of PPH dissolved as compared to the other formulations. It was concluded that PPH OFDTs were formulated successfully with acceptable physical and chemical properties with rapid disintegration in the oral cavity, rapid onset of action, and enhanced patient compliance. It was found that F10 showed good stability upon storage at 25 and 40 °C for 3 months. Formulation of PPH OFDTs can result in a significant improvement in the PPH bioavailability since the first pass metabolism will be avoided.

EVALUATION OF DICLOFENAC SODIUM SUSTAINED RELEASE MATRIX PELLETS: IMPACT OF POLYETHYLENE GLYCOLS MOLECULAR WEIGHT.

Sustained release matrix pellets loaded with 5% w/w diclofenac sodium (DS) were prepared using extrusion/spheronization technique. Different polyethylene glycols (PEGs) of different molecular weight, namely PEG 2000, PEG 4000 and PEG 6000 were mixed with avicel PH 101® in different weight ratios to manufacture the pellet formulations and water was used as a binder. Mix torque rheomter was used to characterize the pellets' wet mass. Also, the prepared pellets were characterized for their particle sizes, DS content, shape and morphology as well as the in vitro drug release. The results showed that increasing PEG weight ratio resulted in a reduction of wet mass torque as well as binder ratio, especially at PEG high weight ratios (30% and 50%) and the extent of lowering wet mass peak torque was inversely proportional to PEG molecular weight. The manufactured pellets exhibited size range of 993 to 1085 µm with small span values. The drug release from pellets was governed by the molecular weight of PEG used, since increasing PEG molecular weight resulted in slowing the drug release rate from pellets, but increasing its level resulted in enhancing release rate. This was attributed to increasing pellet wet mass peak torque by increasing PEG molecular weight and lowering it by increasing PEG level. The prepared pellets showed non-Fickian or anomalous drug release or the coupled diffusion/polymer relaxation.

Engineering erythrocytes as a novel carrier for the targeted delivery of the anticancer drug paclitaxel.

Paclitaxel (PTX) is formulated in a mixture of Cremophor EL and dehydrated alcohol. The intravenous administration of this formula is associated with a risk of infection and hypersensitivity reactions. The presence of Cremophor EL as a pharmaceutical vehicle contributes to these effects. Therefore, in this study, we used human erythrocytes, instead of Cremophor, as a pharmaceutical vehicle. PTX was loaded into erythrocytes using the preswelling method. Analysis of the obtained data indicates that 148.8 µg of PTX was loaded/mL erythrocytes, with an entrapment efficiency of 46.36% and a cell recovery of 75.94%. Furthermore, we observed a significant increase in the mean cell volume values of the erythrocytes, whereas both the mean cell hemoglobin and the mean cell hemoglobin concentration decreased following the loading of PTX. The turbulence fragility index values for unloaded, sham-loaded and PTX-loaded erythrocytes were 3, 2, and 1 h, respectively. Additionally, the erythrocyte glutathione level decreased after PTX loading, whereas lipid peroxidation and protein oxidation increased. The release of PTX from loaded erythrocytes followed first-order kinetics, and about 81% of the loaded drug was released into the plasma after 48 h. The results of the present study revealed that PTX was loaded successfully into human erythrocytes with acceptable loading parameters and with some oxidative modification to the erythrocytes.

Formulation of Folate Receptor-Targeted Silibinin-Loaded Inhalable Chitosan Nanoparticles by the QbD Approach for Lung Cancer Targeted Delivery.

Aim: Targeted delivery of chemotherapeutics by functionalized nanoparticles exhibits a wonderful prospect for cancer treatment. The main objective of this research was to develop folate receptor-targeted silibinin (SB)-loaded inhalable polymeric nanoparticles (FA-CS-SB-NPs) for the treatment of lung cancer. Method: The qbD approach was implemented to prepare SB-loaded nanoparticles. Folic acid was conjugated by electrostatic conjugation in an optimized batch. The therapeutic potentials of formulations were determined using a lung cancer cell-bearing rat model. Result: Optimized formulation exhibited a spherical surface with a mean particle size of 275 ± 1.20 nm, a PDI of 0.234 ± 0.07, a ζ-potential of 32.50 ± 0.21, an entrapment efficiency of 75.52 ± 0.87%, and a CDR of 63.25 ± 1.21% at 48 h. Aerodynamic behaviors such as the mass median aerodynamic diameter (MMAD) and geometric size distribution (GSD) were found to be 2.75 ± 1.02 and 3.15 ± 0.88 µm, respectively. After 24 h of incubation with FA-CS-SB-NPs, the IC50 value was found to be 24.5 g/mL. FA-SB-CS-NPs maintained a significantly higher deposition of SB in lung tissues. Conclusions: Thus, the noninvasive nature and target specificity of FA-CS-SB-NPs pave the way for pulmonary delivery for treating lung cancer.

Influence of polymer blends on the characterization of gliclazide--encapsulated into poly (ε-caprolactone) microparticles.

Gliclazide (GLZ)-loaded microparticles made with a polymeric blend were prepared by a solvent evaporation technique. Organic solutions of two polymers, poly(ε-caprolactone) (PCL) and Eudragit RS (E RS) or ethyl cellulose (EC), in different weight ratios, and 33.3% of GLZ were prepared and dropped into aqueous solution of poly vinyl alcohol, in different experimental conditions, achieving drug-loaded microparticles. The obtained microparticles were characterized in terms of yield of production, shape, size, surface properties, drug content, and in vitro drug release behavior. The physical state of the drugs and the polymer was determined by scanning electron microscopy (SEM), Fourier transform infra red and differential scanning calorimetry. Following the in vitro release studies microparticles made from blends of polymer, PCL/E RS or EC showed slower drug release than microparticles made from single PCL polymer. Surface morphology also revealed presence of porous and spherical structure of microparticles. Microparticles showing sustained release of GLZ were examined in rabbits and plasma GLZ concentrations were calculated using HPLC method of assay.

Thermo-Responsive Sol-Gel-Based Nano-Carriers Containing Terbinafine HCl: Formulation, In Vitro and Ex Vivo Characterization, and Antifungal Activity.

The current research aims to create a sol-gel-based nanocarrier containing terbinafine formulated for transdermal delivery of the drug into the skin. Sol-gel-based nanocarriers were prepared via the cold method using poloxamer-188, poloxamer-407, and distilled water. The prepared formulation was examined for pH, gelation temperature, Fourier transform infrared spectrophotometer (FTIR) analysis, thermal stability analysis, X-ray diffraction (XRD), scanning electron microscopy (SEM), particle size analysis, zeta potential, and anti-microbial activity. The in-vitro drug release study of F1 was found to be 94%, which showed greater drug release as compared to F2 and F3. The pH of the formulation was found to be within the range applicable to the skin. The gelation temperature was detected at 28 °C. The SEM images of formulations have spotted various particles well-segregated from each other. Analysis of formulations showed a mean globule size diameter of 428 nm, zeta potential values of 0.04 mV, refractive index (1.329), and viscosity (5.94 cP). FTIR analysis confirmed various functional groups' presence in the prepared formulation. Thermal analysis has confirmed the stability of the drug within the prepared formulation. The growth of inhibition was found to be 79.2% in 60 min, which revealed that the prepared formulation has shown good permeation from the membrane. Hence, the sol-gel-based nanocarrier formulation of terbinafine was successfully developed and evaluated.

Formulation, Characterization, and Evaluation of ß-Cyclodextrin Functionalized Hypericin Loaded Nanocarriers.

St. John's wort in western Europe has been extensively utilized for the treatment of mild to moderate depression. Hypericin, a red pigment, is found to be responsible for its antidepressant activity. The aim of the current study was to prepare a nanoemulsion (O/W) of hypericin designed for immediate delivery of the drug to the brain for the treatment of depression. The nanoemulsion was prepared by means of a homogenization technique, and that was followed by its physicochemical evaluation. Tween-80, Span-80, ß-cyclodextrin, ethanol, and eucalyptus oil were utilized for the manufacturing of the nanoemulsion. Morphological studies have revealed globular structures of nanosize that were confirmed by the zeta analysis. The consistency of particles was revealed by the low polydispersity values. pH values of all formulations lay within the range of nasal pH. The viscosity of the prepared formulations was affected by the increase in concentrations of ß-cyclodextrin. After passing from the centrifugation and freeze-thaw studies, the prepared formulations showed good stability. Formulation F2 having a composition of oil phase (0.125 mL), aqueous phase (1.25 mL), and ß-cyclodextrin (8%) showed the best results out of all the formulations, and F2 had a pH of 5.7, 5.35 cP viscosity, 1.332 refractive index, 148.8 globule size, and -10.8 zeta potential. The mean percentage drug release and in vitro and ex vivo percentage drug permeations were observed to be 71.75, 76, and 75.07%, respectively. Meanwhile, formulation F2 showed the maximum drug release and permeation. In vivo behavior studies including the open field test, elevated plus maze test, and tail suspension test were conducted to see the antidepressant effect of hypericin along with comparison with a commercially available treatment. In conclusion, the prepared formulation shows good efficacy as an antidepressant and can be considered as a natural alternative over synthetic drugs.

Natural Fatty Acid Guards against Brain Endothelial Cell Death and Microvascular Pathology following Ischemic Insult in the Presence of Acute Hyperglycemia.

Ischemic stroke is worsened by the presence of sudden high blood sugar levels, even in individuals without pre-existing diabetes. This elevated glucose concentration hampers the ability of energy-starved brain cells to efficiently use it as a source of energy. Consequently, this leads to the production of abundant amounts of toxic glucose metabolites, which trigger oxidative stress in the brain milieu, particularly in the microvasculature of the brain. A prominent feature of this oxidative stress is the demise of endothelial cells, causing detrimental changes in blood vessels, including a reduction in their vascular diameter, a decreased efficiency of vessel proliferation, and the impaired integrity of tight junctions. These vascular pathologies contributed to an increase in the volume of damaged tissues (infarct), an exacerbation of brain swelling (edema), and a decline in cognitive and motor functions. In a mouse model of ischemic stroke with induced acute hyperglycemia, a naturally occurring saturated fatty acid provides protective cover to the microvasculature by preventing damage related to oxidative stress. Our current research revealed that lauric acid (LA) attenuated infarct volume and reduced brain edema by reducing endothelial cell death, enhancing vessels' diameter, promoting vascular angiogenesis, and stabilizing barrier functions. Animals administered with this natural compound showed a significant reduction in 4-HNE-positive vessels. In conclusion, natural saturated fatty acids help to preserve brain microvascular functions following ischemic insults in the presence of acute hyperglycemia.

A multi-class deep learning model for early lung cancer and chronic kidney disease detection using computed tomography images.

Lung cancer is a fatal disease caused by an abnormal proliferation of cells in the lungs. Similarly, chronic kidney disorders affect people worldwide and can lead to renal failure and impaired kidney function. Cyst development, kidney stones, and tumors are frequent diseases impairing kidney function. Since these conditions are generally asymptomatic, early, and accurate identification of lung cancer and renal conditions is necessary to prevent serious complications. Artificial Intelligence plays a vital role in the early detection of lethal diseases. In this paper, we proposed a modified Xception deep neural network-based computer-aided diagnosis model, consisting of transfer learning based image net weights of Xception model and a fine-tuned network for automatic lung and kidney computed tomography multi-class image classification. The proposed model obtained 99.39% accuracy, 99.33% precision, 98% recall, and 98.67% F1-score for lung cancer multi-class classification. Whereas, it attained 100% accuracy, F1 score, recall and precision for kidney disease multi-class classification. Also, the proposed modified Xception model outperformed the original Xception model and the existing methods. Hence, it can serve as a support tool to the radiologists and nephrologists for early detection of lung cancer and chronic kidney disease, respectively.

Anti-Arthritic and Immunomodulatory Potential of Methanolic, n-Hexane, and Ethyl Acetate Fractions of Bark of Acacia modesta on Complete Freund's Adjuvant-Induced Arthritis in Rats.

Rheumatoid arthritis is an autoimmune disorder and topic of interest for researchers due to its increasing frequency and limited treatment. Acacia modesta Wall is known to treat rheumatic disorders in the traditional system of medicinal plants. Traditional medicines are still required for the treatment of this disease due to the large number of side-effects caused by commercial medicines. In the current study, the antiarthritic potential of methanolic extract (AM-metha), n-hexane (AM-hexa) fraction, and ethyl acetate (AM-etha) fraction of the bark of A. modesta against a complete Freund's adjuvant rat model was evaluated. Evaluation using a digital plethysmometer, macroscopic evaluation, and histopathological evaluation were conducted to determine the paw volume and arthritic scoring. ELISA was performed to assess the PGE2 levels. RT-PCR was used to evaluate the expression levels of MMP2, MMP3, MMP9, NF-κB, IL6, IL1ß, TNFα, and VEGF. Biochemical and hematological analyses were also conducted. GC/MS was also carried out to analyze the presence of medicinal compounds. The data revealed a marked reduction in the paw volume, arthritic scoring, and histopathological parameters, indicating the anti-arthritic potential of the plant. Treatment with plant extracts and fractions markedly down-regulated MMP2, MMP3, MMP9, NF-κB, IL6, IL1ß, TNFα, and VEGF levels. Similarly, PGE2 levels were also found to be ameliorated in the treatment groups, indicating the immunomodulatory property of plant bark. Plant treatment nearly normalized hematological parameters such as counts of WBCs, RBCs, and platelets, along with Hb content, thereby validating the anti-arthritic activity. GC/MS analysis disclosed the presence of strong anti-inflammatory compounds such as lupeol, oleic acid, and squalene. The study showed that A. modesta possesses anti-arthritic and immunomodulatory potential linked to significant down-regulation of pro-inflammatory and inflammatory biomarkers.

Lamotrigine-Loaded Poloxamer-Based Thermo-Responsive Sol-Gel: Formulation, In Vitro Assessment, Ex Vivo Permeation, and Toxicology Study.

The present study aimed to prepare, characterize, and evaluate a thermo-responsive sol-gel for intranasal delivery of lamotrigine (LTG), which was designed for sustained drug delivery to treat epilepsy. LTG sol-gel was prepared using the cold method by changing the concentrations of poloxamer 407 and poloxamer 188, which were used as thermo-reversible polymers. The optimized formulations of sol-gel were analyzed for clarity, pH, viscosity, gelation temperature, gelation time, spreadability, drug content, in vitro drug release studies, ex vivo permeation studies, and in vivo toxicological studies. FTIR, XRD, and DSC were performed to determine the thermal stability of the drug and polymers. The prepared formulations had a clear appearance in sol form; they were liquid at room temperature and became gel at temperatures between 31 °C and 36 °C. The pH was within the range of the nasal pH, between 6.2 and 6.4. The drug content was found to be between 92% and 94%. In vitro drug release studies indicated that the formulations released up to 92% of the drug within 24 h. The FTIR, DSC, and XRD analyses showed no interaction between the drug and the polymer. A short-term stability study indicated that the formulation was stable at room temperature and at 4-8 °C. There was a slight increase in viscosity at room temperature, which may be due to the evaporation of the vehicle. A histological study indicated that there were no signs of toxicity seen in vital organs, such as the brain, kidney, liver, heart, and spleen. It can be concluded from the above results that the prepared intranasal sol-gel for the delivery of LTG is safe for direct nose-to-brain delivery to overcome the first-pass effect and thus enhance bioavailability. It can be considered an effective alternative to conventional drug delivery for the treatment of epilepsy.

Exploring the Synthetic Chemistry of Phenyl-3-(5-aryl-2-furyl)- 2-propen-1-ones as Urease Inhibitors: Mechanistic Approach through Urease Inhibition, Molecular Docking and Structure-Activity Relationship.

Furan chalcone scaffolds belong to the most privileged and promising oxygen-containing heterocyclic class of compounds, which have a wide spectrum of therapeutic applications in the field of pharmaceutics, pharmacology, and medicinal chemistry. This research described the synthesis of a series of twelve novel and seven reported furan chalcone (conventional synthetic approach) analogues 4a-s through the application of microwave-assisted synthetic methodology and evaluated for therapeutic inhibition potential against bacterial urease enzyme. In the first step, a series of nineteen substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were achieved in moderate to good yields (40-70%). These substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were condensed with acetophenone via Claisen-Schmidt condensation to furnish 19 substituted furan chalcone scaffolds 4a-s in excellent yields (85-92%) in microwave-assisted synthetic approach, while in conventional methodology, these furan chalcone 4a-s were furnished in good yield (65-90%). Furan chalcone structural motifs 4a-s were characterized through elemental analysis and spectroscopic techniques. These nineteen (19)-afforded furan chalcones 4a-s were screened for urease inhibitory chemotherapeutic efficacy and most of the furan chalcones displayed promising urease inhibition activity. The most active urease inhibitors were 1-phenyl-3-[5-(2',5'-dichlorophenyl)-2-furyl]-2-propen-1-one 4h with an IC50 value of 16.13 ± 2.45 µM, and 1-phenyl- 3-[5-(2'-chlorophenyl)-2-furyl] -2-propen-1-one 4s with an IC50 value of 18.75 ± 0.85 µM in comparison with reference drug thiourea (IC50 = 21.25 ± 0.15 µM). These furan chalcone derivatives 4h and 4s are more efficient urease inhibitors than reference drug thiourea. Structure-activity relationship (SAR) revealed that the 2,5-dichloro 4h and 2-chloro 4s moiety containing furan chalcone derivatives may be considered as potential lead reagents for urease inhibition. The in silico molecular docking study results are in agreement with the experimental biological findings. The results of this study may be helpful in the future drug discovery and designing of novel efficient urease inhibitory agents from this biologically active class of furan chalcones.

Suppression of Nasopharyngeal and Gastric Tumor Growth in a Mouse Model by Antibodies to Epstein-Barr Virus LMP1 Protein.

The study aimed to investigate the antitumor efficacy of anti-LMP1 antibodies in EBV-positive nasopharyngeal and stomach cell lines and xenograft models. The study also examined the NF-κB expression and cell cycle activation of NPC-serum-exosome-associated LMP1. Anti-LMP1 antibody treatment before or during cell implantation prevented tumor growth in nude mice. A small dose of antibodies resulted in complete tumor regression for at least three months after the tumors had grown in size. The consumption of antigen-antibody complexes by tumor cells limited tumor growth. In vitro experiments showed that anti-LMP1 antibodies killed EBV-positive NPC- or GC-derived epithelial cell lines and EBV-positive human B-cell lines but not EBV-negative cell lines. Treatment with anti-LMP1 reduced NF-κB expression in cells. The animal model experiments showed that anti-LMP1 inhibited and prevented NPC- or GC-derived tumor growth. The results suggest that LMP1 antibody immunotherapy could cure nasopharyngeal cancer, EBV-positive gastric carcinoma, and EBV-associated lymphomas. However, further validation of these findings is required through human clinical trials.

Formulation and Characterization of Curcumin Niosomes: Antioxidant and Cytotoxicity Studies.

Curcumin's applications in the treatment of conditions including osteoarthritis, dementia, malignancies of the pancreas, and malignancies of the intestines have drawn increasing attention. It has several wonderful qualities, including being an anti-inflammatory agent, an anti-mutagenic agent, and an antioxidant, and has substantially reduced inherent cytotoxicity outcomes. Although curcumin possesses multiple known curative properties, due to its limited bioavailability, it is necessary to develop efficient strategies to overcome these hurdles. To establish an effective administration method, various niosomal formulations were optimized using the Box-Behnken design and assessed in the current investigation. To examine the curcumin niosomes, zeta sizer, zeta potential, entrapment efficiency, SEM, antioxidant potential, cytotoxicity, and release studies were performed. The optimized curcumin niosomes exhibited an average particle size of 169.4 nm, a low PDI of 0.189, and high entrapment efficiency of 85.4%. The release profile showed 79.39% curcumin after 24 h and had significantly higher antioxidant potential as compared with that of free curcumin. The cytotoxicity results of curcumin niosomes presented increased mortality in human ovarian cancer A2780.