Synthesis biological evaluation and molecular docking of isatin hybrids as anti-cancer and anti-microbial agents.

Isatin, known as 1H-indole-2,3-dione, was originally recognised as a synthetic molecule until its discovery in the fruits of the cannonball tree, Couroupita guianensis. It is naturally occurring in plants of the genus Isatis and serves as a metabolic derivative of adrenaline in humans. Isatin possesses significant pharmacological importance, and its synthetic versatility has prompted extensive interest in its derivative compounds due to their diverse biological and pharmacological properties. These derivatives represent a valuable class of heterocyclic compounds with potential applications as precursors for synthesizing numerous valuable drugs. In the pursuit of advancing our research on isatin hybrids, we investigate the utilisation of readily available hydrazonoindolin-2-one and isatin as starting materials for the synthesis of a wide range of analogues. Characterisation of the synthesized compounds was carried out through various analytical techniques. Furthermore, the obtained compounds were subjected to extensive testing to evaluate their anticancer and antimicrobial activities. Specifically, their efficacy against key proteins, namely Staphylococcus aureus protein (PDB ID: 1JIJ), Escherichia coli protein (PDB ID: 1T9U), Pseudomonas aeruginosa protein (PDB ID: 2UV0), and Acinetobacter baumannii protein (PDB ID: 4HKG), was examined through molecular docking calculations. Several molecules, such as 3, 4, 6, 16, and 19, displayed remarkable activity against the renal cancer cell line UO-31. Additionally, the results of antimicrobial activity testing revealed that compound 16 exhibited significant cytotoxicity against Candida albicans and Cryptococcus neoformans. Subsequently, ADME/T calculations were performed to gain insights into the potential effects and reactions of these molecules within human metabolism. This comprehensive study provides valuable insights into the potential pharmacological applications of isatin derivatives and underscores their significance in drug development.

HSPiP, Computational, and Thermodynamic Model-Based Optimized Solvents for Subcutaneous Delivery of Tolterodine Tartrate and GastroPlus­Based In Vivo Prediction in Humans: Part II.

In part I, we reported Hansen solubility parameters (HSP, HSPiP program), experimental solubility at varied temperatures for TOTA delivery. Here, we studied dose volume selection, stability, pH, osmolality, dispersion, clarity, and viscosity of the explored combinations (I-VI). Ex vivo permeation and deposition studies were performed to observe relative diffusion rate from the injected site in rat skin. Confocal laser scanning microscopy (CLSM) study was conducted to support ex vivo findings. Moreover, GastroPlus predicted in vivo parameters in humans and the impact of various critical factors on pharmacokinetic parameters (PK). Immediate release product (IR) contained 60% of PEG400 whereas controlled release formulation (CR) contained PEG400 (60%), water (10%) and d-limonene (30%) to deliver 2 mg of TOTA. GastroPlus predicted the plasma drug concentration of weakly basic TOTA as function of pH (from pH 2.0 to 9). The cumulative drug permeation and drug deposition were found to be in the order as B-VI˃ C-VI˃A-VI across rat skin. This finding was further supported with CLSM. Moreover, IR and CR were predicted to achieve Cmax of 0.0038 µg/ mL and 0.00023 µg/mL, respectively, after sub-Q delivery. Added limonene in CR extended the plasma drug concentration over period of 12 h as predicted in GastroPlus. Parameters sensitivity analysis (PSA) assessment predicted that sub-Q blood flow rate is the only factor affecting PK parameters in IR formulation whereas this was insignificant for CR. Thus, sub-Q delivery CR would be promising alternative with ease of delivery to children and aged patient.

Potentially active aspirin derivative to release nitric oxide: In-vitro, in-vivo and in-silico approaches.

The series of newer salicylate derivatives incorporating nitroxy functionality were synthesized and evaluated for their potential effect in gastrointestinal (GI) related toxicity produced by aspirin. The synthesized compounds (5a-j) were subjected to %NO (nitric oxide) release study, in-vitro anti-inflammatory potential, % inhibition of carrageenan-induced paw edema and the obtained results were validated by in-silico studies including molecular docking, MD simulations and in-silico ADME (absorption, distribution, metabolism, and elimination) calculations. Compounds 5a (20.86 %) and 5g (18.20 %) displayed the highest percentage of NO release in all the tested compounds. Similarly, 5a and 5h were found to have (77.11 % and 79.53 %) &(78.56 % and 66.10 %) inhibition in carrageenan induced paw edema in animal mode which were relatively higher than ibuprofen (standard used). The obtained results were validated by molecular docking and MD simulations studies. The molecular docking study of 5a and 5h revealed that docking scores were also obtained in very close proximity of -8.35, -9.67 and -8.48 for ibuprofen, 5g and 5h respectively. In MD simulations studies, the calculated lower RMSD (root mean square deviation) values 2.8 Å and 5.6 Å for 5g and 5h, respectively indicated the stability of ligand-protein complexes. Similarly lower RSMF (root mean square fluctuation) values indicated the molecules remained in the active pocket throughout the entire MD simulations run. Further, in-silico ADME calculations were determined and all compounds obey the Lipinski's rule of five and it was predicted that these molecules would be orally active without any serious toxic effect.

A correlation between oxidative stress and diabetic retinopathy: An updated review.

Oxidative stress (OS) is a cytopathic outcome of excessively generated reactive oxygen species (ROS), down regulated antioxidant defense signaling pathways, and the imbalance between the produced radicals and their clearance. It plays a role in the genesis of several illnesses, especially hyperglycemia and its effects. Diabetic retinal illness, a micro vascular side effect of the condition, is the prime reason of diabetic related blindness. The OS (directly or indirectly) is associated with diabetic retinopathy (DR) and related consequences. The OS is responsible to induce and interfere the metabolic signaling pathways to enhance influx of the polyol cascades and hexosamine pathways, stimulate Protein Kinase-C (PKC) variants, and accumulate advanced glycation end products (AGEs). Additionally, the inequity between the scavenging and generation of ROS is caused by the epigenetic alteration caused by hyperglycemia that suppresses the antioxidant defense system. Induced by an excessive buildup of ROS, retinal changes in structure and function include mitochondrial damage, cellular death, inflammation, and lipid peroxidation. Therefore, it is crucial to comprehend and clarify the mechanisms connected to oxidative stress that underlie the development of DR.

Identification of Potential Antitubulin Agents with Anticancer Assets from a Series of Imidazo[1,2-a]quinoxaline Derivatives: In Silico and In Vitro Approaches.

Computer-aided drug design is a powerful and promising tool for drug design and development, with a reduced cost and time. In the current study, we rationally selected a library of 34 fused imidazo[1,2-a]quinoxaline derivatives and performed virtual screening, molecular docking, and molecular mechanics for a lead identification against tubulin as an anticancer molecule. The computational analysis and pharmacophoric features were represented as 1A2; this was a potential lead against tubulin, with a maximized affinity and binding score at the colchicine-binding site of tubulin. The efficiency of this lead molecule was further identified using an in vitro assay on a tubulin enzyme and the anticancer potential was established using an MTT assay. Compound 1A2 (IC50 = 4.33-6.11 µM against MCF-7, MDA-MB-231, HCT-116, and A549 cell lines) displayed encouraging results similar to the standard drug colchicine in these in vitro studies, which further confirmed the effectiveness of CADD in new drug developments. Thus, we successfully applied the utility of in silico techniques to identify the best plausible leads from the fused azaheterocycles.

HSPiP and QbD Program-Based Analytical Method Development and Validation to Quantify Ketoconazole in Dermatokinetic Study.

Ketoconazole (KTZ) is the most potential azole anti-mycotic drug. The quantification of KTZ from various layers of the skin after topical application of lipidic nanocarriers is critical. We addressed a sensitive, specific, simple, rapid, reproducible, and economic analytical method to quantify KTZ from the treated skin homogenate using the Hansen solubility parameter (HSP, HSPiP software)-based modeling and experimental design. The software provided various HSP values for KTZ and solvents to compose the mobile phase. The Taguchi model identified the significant sets of factors to develop a robust bioanalytical method with reduced variability. In the optimization, acetonitrile (ACN) concentration (X1 as A) and the pH of mobile phase (X2 as B) were two factors against two responses (Y1: peak area and Y2: retention time). The HPLC (high-performance liquid chromatography) method validation was carried out based on US-FDA guidelines for the developed KTZ formulations (suspension, solid nanoparticles, and commercial product) extracted from the treated rat skin. The experimental solubility of KTZ was found to be maximum in the two solvents (ACN and ethyl acetate), based on HSP values. Surface response methodology (SRM) identified remarkable impact of ACN concentration and the mobile phase pH on the peak area and retention time. Analytical limits (0.17 and 0.50 µg/mL) were established for KTZ-SLNs (extracted from the skin). The method was implemented with high reproducibility, accuracy, and selectivity to quantify KTZ from the treated rat skin.

Constituents, Antibacterial Adhesion, Cytotoxic and in Vitro Metastasis Blocking Properties of Salvia fruticosa Essential Oils from Three Palestinian Localities.

Essential oils (EOs) of Salvia fruticosa Mill. gathered from three Palestinian localities were studied to determine their constituents, antibacterial adhesion impact against Klebsiella pneumonia, cytotoxicity, and their function in cancer cell migration. Gas chromatography-mass spectrometry identified the chemical components, while the MTT technique was used to measure the EOs' cytotoxicity against HeLa (cervical) and Caco-2 (colorectal) cancer cells. Antibacterial adhesion was assessed by examining Klebsiella pneumoniae's ability to adhere to Caco-2 cells. Our study found that eucalyptol was present as the main constituent in all S. fruticosa EOs. In addition, K. pneumoniae adhesion and metastasis were reduced after 48 h of application. Salfit's and Hebron's EOs had the most potent cytotoxic effects on Caco-2 and HeLa, with IC50 values in the range of 0.7-1.3 µg/mL. Taking into account the obtained results, it may be concluded that S. fruticosa EOs can serve as potential disinfectant agents for the treatment and prevention of K. pneumoniae-associated illness and cancer.

Mediterranean diet diminishes the effects of Crohn's disease and improves its parameters: A systematic review.

BACKGROUND: The pathogenesis and clinical course of Crohn's disease (CD) is influenced by diet. Mediterranean Diet (MD) helps Crohn's patients through many mechanisms. AIMS: This study aimed to evaluate the effect of the MD on CD patients and to evaluate such effect on body parameters. METHODS: PubMed, Science Direct, Web of Science, MEDLINE and Cochrane central library were searched for MD and CD from 2010 to 2020. Included studies met the following criteria: (1) male and female adults (18-75 years) with a confirmed diagnosis of CD; (2) MD as an intervention; (3) original interventional Trial, Cross-Sectional Analysis, or Prospective Cohort Studies. RESULTS: Five studies were included, involving 83,564 participants. A small number of patients with CD fulfilled the P-MDS criteria, the overall scores were low, 4.7 and 4.5 for females and males respectively. Patients with an inactive disease whose adherence to MD was greater, the MD score was negatively correlated with disease activity (p <0.001) and positively with IBDQ (p = 0.008). Twenty-seven percent had a prevalence of impaired adherence to a MD (mMED score = 0-2), giving such a population a risk attributed to 12% for the later CD. Seventy-point reduction in CDAI + decreased fecal CRP / calprotectin, calprotectin <250 mcg/gm or >50% decrease from baseline and hsCRP < 5 mg/L or >50% from baseline. CONCLUSIONS: MD showed anti-inflammatory properties. Adherence to MD was associated with improvement in CD patients and negatively correlated with the disease activity, in addition to a lower risk of developing CD later in life.

Hydroethanolic Extract of Urtica dioica L. (Stinging Nettle) Leaves as Disaccharidase Inhibitor and Glucose Transport in Caco-2 Hinderer.

Herbal treatment for diabetes mellitus is widely used. The pharmacological activity is thought to be due to the phenolic compounds found in the plant leaves. The present study aims to investigate the phytochemical composition of Urtica dioica (UD) hydroethanolic extract and to screen its antidiabetic activity by disaccharidase hindering and glucose transport in Caco-2 cells. The results have shown that a total of 13 phenolic compounds in this work, viz. caffeic and coumaric acid esters (1, 2, 4-7, 10), ferulic derivative (3), and flavonoid glycosides (8, 9, 11-13), were identified using HPLC-DAD-ESI/MS2. The most abundant phenolic compounds were 8 (rutin) followed by 6 (caffeoylquinic acid III). Less predominant compounds were 4 (caffeoylquinic acid II) and 11 (kaempferol-O-rutinoside). The UD hydroethanolic extract showed 56%, 45%, and 28% (1.0 mg/mL) inhibition level for maltase, sucrase, and lactase, respectively. On the other hand, glucose transport was 1.48 times less at 1.0 mg/mL UD extract compared with the control containing no UD extract. The results confirmed that U. dioica is a potential antidiabetic herb having both anti-disaccharidase and glucose transport inhibitory properties, which explained the use of UD in traditional medicine.

Formulation of Piperine-Chitosan-Coated Liposomes: Characterization and In Vitro Cytotoxic Evaluation.

The present research work is designed to prepare and evaluate piperine liposomes and piperine-chitosan-coated liposomes for oral delivery. Piperine (PPN) is a water-insoluble bioactive compound used for different diseases. The prepared formulations were evaluated for physicochemical study, mucoadhesive study, permeation study and in vitro cytotoxic study using the MCF7 breast cancer cell line. Piperine-loaded liposomes (PLF) were prepared by the thin-film evaporation method. The selected liposomes were coated with chitosan (PLFC) by electrostatic deposition to enhance the mucoadhesive property and in vitro therapeutic efficacy. Based on the findings of the study, the prepared PPN liposomes (PLF3) and chitosan coated PPN liposomes (PLF3C1) showed a nanometric size range of 165.7 ± 7.4 to 243.4 ± 7.5, a narrow polydispersity index (>0.3) and zeta potential (-7.1 to 29.8 mV). The average encapsulation efficiency was found to be between 60 and 80% for all prepared formulations. The drug release and permeation study profile showed biphasic release behavior and enhanced PPN permeation. The in vitro antioxidant study results showed a comparable antioxidant activity with pure PPN. The anticancer study depicted that the cell viability assay of tested PLF3C2 has significantly (p < 0.001)) reduced the IC50 when compared with pure PPN. The study revealed that oral chitosan-coated liposomes are a promising delivery system for the PPN and can increase the therapeutic efficacy against the breast cancer cell line.

Experimental Solubility, Thermodynamic/Computational Validations, and GastroPlus-Based In Silico Prediction for Subcutaneous Delivery of Rifampicin.

We focused to explore a suitable solvent for rifampicin (RIF) recommended for subcutaneous (sub-Q) delivery [ethylene glycol (EG), propylene glycol (PG), tween 20, polyethylene glycol-400 (PEG400), oleic acid (OA), N-methyl-2-pyrrolidone (NMP), cremophor-EL (CEL), ethyl oleate (EO), methanol, and glycerol] followed by computational validations and in-silico prediction using GastroPlus. The experimental solubility was conducted over temperature ranges T = 298.2-318.2 K) and fixed pressure (p = 0.1 MPa) followed by validation employing computational models (Apelblat, and van't Hoff). Moreover, the HSPiP solubility software provided the Hansen solubility parameters. At T = 318.2K, the estimated maximum solubility (in term of mole fraction) values of the drug were in order of NMP (11.9 × 10-2) ˃ methanol (6.8 × 10-2) ˃ PEG400 (4.8 × 10-2) ˃ tween 20 (3.4 × 10-2). The drug dissolution was endothermic process and entropy driven as evident from "apparent thermodynamic analysis". The activity coefficients confirmed facilitated RIF-NMP interactions for increased solubility among them. Eventually, GastroPlus predicted the impact of critical input parameters on major pharmacokinetics responses after sub-Q delivery as compared to oral delivery. Thus, NMP may be the best solvent for sub-Q delivery of RIF to treat skin tuberculosis (local and systemic) and cutaneous related disease at explored concentration.

Experimental Solubility of Ketoconazole, Validation Models, and In vivo Prediction in Human Based on GastroPlus.

The study aimed to identify a suitable cosolvent + water mixture for subcutaneous (sub-Q) delivery of ketoconazole (KETO). The solubility was assessed for several dimethyl acetamide (DMA) + water mixtures at T = 293.2 to 318.2 K and pressure P = 0.1 MPa. The experimental solubility (xe) was validated using the Van 't Hoff and Yalkowsky models and functional thermodynamic parameters (enthalpy ΔsolH°, entropy ΔsolS°, and Gibbs free energy ΔsolG°). The in vitro drug release study was performed at physiological pH, and the data served as the input to GastroPlus, which predicted the in vivo performance of KETO dissolved in a DMA + water cosolvent mixture for sub-Q delivery in human. The maximum solubility (mole fraction) of KETO (9.81 × 10-1) was obtained for neat DMA at 318.2 K whereas the lowest value (1.7 × 10-5) was for pure water at 293.2 K. An apparent thermodynamic analysis based on xe gave positive values for the functional parameters. KETO dissolution requires energy, as evidenced by the high positive values of ΔsolH° and ΔsolG°. Interestingly, ΔsolG° progressively decreased with increasing concentration of DMA in the DMA + water mixture, suggesting that the DMA-based molecular interaction improved the solubilization. Positive values of ΔsolG° and ΔsolS° for each DMA + water cosolvent mixture corroborated the endothermic and entropy-driven dissolution. GastroPlus predicted better absorption of KETO through sub-Q delivery than oral delivery. Hence, the DMA + water mixture may be a promising system for sub-Q delivery of KETO to control topical and systemic fungal infections.

Formulation of Gelucire®-Based Solid Dispersions of Atorvastatin Calcium: In Vitro Dissolution and In Vivo Bioavailability Study.

Atorvastatin (ATV) is a poorly water-soluble drug that exhibits poor oral bioavailability. Therefore, present research was designed to develop ATV solid dispersions (SDs) to enhance the solubility, drug release, and oral bioavailability. Various SDs of ATV were formulated by conventional and microwave-induced melting methods using Gelucire®48/16 as a carrier. The formulated SDs were characterized for different physicochemical characterizations, drug release, and oral bioavailability studies. The results obtained from the different physicochemical characterization indicate the molecular dispersion of ATV within various SDs. The drug polymer interaction results showed no interaction between ATV and used carrier. There was marked enhancement in the solubility (1.95-9.32 folds) was observed for ATV in prepared SDs as compare to pure ATV. The drug content was found to be in the range of 96.19% ± 2.14% to 98.34% ± 1.32%. The drug release results revealed significant enhancement in ATV release from prepared SDs compared to the pure drug and the marketed tablets. The formulation F8 showed high dissolution performance (% DE30 value of 80.65 ± 3.05) among the other formulations. Optimized Gelucire®48/16-based SDs formulation suggested improved oral absorption of atorvastatin as evidenced with improved pharmacokinetic parameters (Cmax 2864.33 ± 573.86 ng/ml; AUC0-t 5594.95 ± 623.3 ng/h ml) as compared to ATV suspension (Cmax 317.82 ± 63.56 ng/ml; AUC0-t 573.94 ± 398.9 ng/h ml) and marketed tablets (Cmax 852.72 ± 42.63 ng/ml; 4837.4 ± 174.7 ng/h ml). Conclusively, solid dispersion-based oral formulation of atorvastatin could be a promising approach for enhanced drug solubilization, dissolution, and subsequently improved absorption.

Black Edible Films from Protein-Containing Defatted Cake of Nigella sativa Seeds.

Black biodegradable/edible protein-based films were prepared from defatted cake waste obtained from Nigella sativa (black cumin) seeds as by-product of oil extraction process. The effects of pH, glycerol concentrations, and transglutaminase-catalyzed protein cross-linking activity on the stability of film-forming solutions were studied to determine the best experimental conditions to produce handleable films. Proteins contained in the analyzed defatted cake were shown to be able to act as transglutaminase acyl donor and acceptor substrates being polymerized when incubated in vitro in the presence of the enzyme. Film-forming solutions containing 20% glycerol and casted at pH 8.0 after treatment with the enzyme gave rise to morphologically more homogeneous films possessing mechanical and barrier properties, as well as antimicrobial activity, compatible with their possible applications as food packaging materials and mulching sheets. These findings confirm the validity of the strategy to consider the seed oil processed cakes as protein-based renewable sources to produce not only fertilizers, animal feed, or culinary food but also further valuable products such as bioplastics.

Formulation and Evaluation of Supramolecular Food-Grade Piperine HP ß CD and TPGS Complex: Dissolution, Physicochemical Characterization, Molecular Docking, In Vitro Antioxidant Activity, and Antimicrobial Assessment.

The purpose of the present study was to improve the aqueous solubility, dissolution, and antioxidant activity of the water-insoluble drug piperine (PIP). The study was performed by preparing PIP binary inclusion complex (PIP BIC) and piperine ternary inclusion complex (PIP TIC) by different methods. The effect of a hydrophilic auxiliary substance (TPGS) was assessed with addition to PIP and hydroxypropyl beta cyclodextrin (HP ß CD) complex. The phase solubility study was performed to evaluate the complexation efficiency and stability constant. The aqueous solubility, dissolution, physicochemical assessment, antioxidant activity, antimicrobial activity, and molecular docking were further evaluated to check the effect of the complexation of PIP. The stability constant (Ks) value was found to be 238 and 461 M-1 for the binary and ternary inclusion complex. The dissolution study results showed a marked enhancement of release in comparison to pure drug. XRD and SEM studies revealed the presence of more agglomerated and amorphous structures of PIP, which confirmed the formation of complexes. The results of DPPH radical scavenging and antimicrobial activity showed a significant (p < 0.05) enhancement in scavenging activity for PIP TIC (microwave irradiation (MI)). The docking studies have revealed that the binding affinity of TPGS at the PIP-HP ß CD complex was -5.2 kcal/mol.

Development and Optimization of Epigallocatechin-3-Gallate (EGCG) Nano Phytosome Using Design of Experiment (DoE) and Their In Vivo Anti-Inflammatory Studies.

Inflammation is responsible for the development of many diseases that make up a significant cause of death. The purpose of the study was to develop a novel nanophytosomal preparation of epigallocatechin-3-gallate (EGCG) and egg phospholipid complex that has a lower particle size with higher drug loading capability, physical stability and anti-inflammatory activities. The impact of different factors and material characteristics on the average particle size was studied along with the drug loading of phytosome using design of experiment (DoE). The in vivo anti-inflammatory study was evaluated using a rat model to investigate the performance of EGCG nanophytosome. UHPLC results showed that 500 µg of EGCG were present in 1 mL of green tea extract. SEM data exhibited that phytosome (phospholipid-drug complex) was in the nanosize range, which was further evident from TEM data. Malvern Zetasizer data showed that the average particle size of the EGCG nanophytosome was in the range of 100-250 nm. High drug loading (up to 90%) was achieved with optimum addition rate, stirring temperature and phospholipid concentration. Stability study data suggest that no significant changes were observed in average particle size and drug loading of nanophytome. The in vivo anti-inflammatory study indicated a significant anti-inflammatory activity of green tea extract, pure EGCG and its phytosomal preparations (p ≤ 0.001) against acute paw edema.

Stimulatory Effects of Soluplus® on Flufenamic Acid ß-Cyclodextrin Supramolecular Complex: Physicochemical Characterization and Pre-clinical Anti-inflammatory Assessment.

The present study demonstrates the solubility and dissolution of flufenamic acid (FLF)/ß-cyclodextrin (ß-CD)/Soluplus® supramolecular ternary inclusion complex. The binary and ternary inclusion complexes were prepared using solvent evaporation and the microwave irradiation method. The prepared inclusion complexes were evaluated for physicochemical characterization and anti-inflammatory activity using a murine paw edema mol. The phase solubility studies demonstrated 4.59-fold and 17.54-fold enhancements in FLF solubility with ß-CD alone and ß-CD:Soluplus® combination compared with pure FLF, respectively. The in vitro drug release results revealed a significant improvement (P < 0.05) in the release pattern compared with pure FLF. Maximum release was found with flufenamic acid binary and ternary complexes prepared using the microwave irradiation method, i.e., 75.23 ± 3.12% and 95.36 ± 3.23% in 60 min, respectively. The physicochemical characterization results showed complex formation and conversion of the crystalline form of FLF to an amorphous form. The SEM study revealed the presence of a more agglomerated and amorphous structure of the solid particles, which confirmed the formation of complexes. The anti-inflammatory effect of the complex was higher than pure FLF. Therefore, the FLF:ß-CD:Soluplus® inclusion complex may be a very valuable formulation with improved solubility, dissolution, and anti-inflammatory effect.

Prevalence of underweight, overweight and obesity among Palestinian school-age children and the associated risk factors: a cross sectional study.

BACKGROUND: Childhood obesity is rising in developed and developing countries, while childhood underweight is rising mainly in developing countries. Childhood underweight has been shown to increase a child's risk of rapid weight gain. Overweight and obese children are more likely to become obese adults, which increases the risk of type-II diabetes and cardiovascular diseases. Studies concerning obesity among Palestinian children are scarce. The prevalence of obesity among Palestinian children has increased from 3 to 6% within 5 years in comparison to the worldwide rise from 1 to 7%, within 41 years. We aim to determine the current prevalence of underweight, overweight and obesity among Palestinian school-age children and to assess the role of dietary and sociodemographic factors. METHODOLOGY: A cross sectional study was conducted in Palestine in 2017. A total of 1320 school-age children and their 2640 corresponding parents were recruited. A written questionnaire was filled out by the parents. Anthropometric indices were measured and categorized according to the Center for Disease Control and prevention (CDC). RESULTS: The mean ± SD age of the children was 9.5 ± 1.5 years and 48.8% were females. The prevalence of underweight, overweight and obesity among the children was approximately 7.3% (95% CI = 5.9-8.8%), 14.5% (95% CI = 12.7-16.6%) and 15.7% (95% CI = 13.8-17.8%) respectively. Multinomial logistic regression analysis demonstrated a significant correlation of waist circumference, age, gender and living place with the body mass indexes of the students. CONCLUSION: Our findings highlighted the accelerated increase in the prevalence of underweight, overweight and obesity (37.5%) among Palestinian children within a very short time in comparison to the globe. Therefore, Interventions aiming to prevent obesity and underweight at an early stage might be vital to avoid obesity later in life and its health-related co-morbidities, e.g. type-II diabetes and cardiovascular diseases.

Development and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for curcumin transdermal delivery: an anti-inflammatory exposure.

The purpose of this work is to develop novel lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) as carriers for transdermal delivery of curcumin. SNEDDS containing black seed oil, medium chain mono- and diglycerides and surfactants, were prepared as curcumin delivery vehicles. Their formation spontaneity, morphology, droplet size, and drug loading were evaluated. Gel preparation containing two of the SNEDDS formulations were used in the carrageenan induced paw edema to evaluate the anti-inflammatory effect. Results showed droplet size as low as 71 nm. The highest drug loading was observed with SNEDDS-F6 of ∼45 mg/g. In in-vivo investigation, SNEDDS-F6 exhibited significant anti-inflammatory activities in terms of 80% reduction in paw edema when compared with positive control. The prepared SNEDDS with the elevated entrapment efficiency, good transdermal penetration ability could be a suitable candidate for effective transdermal curcumin skin delivery.

Rat palatability, pharmacodynamics effect and bioavailability of mefenamic acid formulations utilizing hot-melt extrusion technology.

Mefenamic acid (MA) has been reported as a weakly soluble drug which presents weak in vivo absorption upon oral administration using conventional formulations. Solid dispersions (SDs) have been investigated extensively in literature for enhancing the solubility and bioavailability of weakly-soluble molecules. Hence, the aim of proposed study was to prepare MA novel formulations in the form of SDs using hot-melt extrusion technology in order to enhance its palatability, bioavailability, and pharmacodynamics effects/anti-inflammatory efficacy. Various SDs of MA were prepared using hot-melt extrusion technology, characterized physically and investigated for dissolution tests. Optimized SD formulations of MA were being subjected to palatability, pharmacodynamics, and pharmacokinetic studies in rats. Optimized SD of MA showed significant rat palatability tastes as compared with pure and marketed MA (p < .05). Anti-inflammatory efficacy of 20% SD and 25% SD of MA was found to be 86.44 and 89.83%, respectively, in comparison with 74.57 and 78.24% by pure MA and marketed MA, respectively. The anti-inflammatory efficacy of optimized SD was found to be significant as compared with pure and marketed MA (p < .05). The oral absorption of MA from optimized 20% SD was also noted as statistically significant as compared with pure MA (p < .05). The relative bioavailability of MA from 20 and 25% SDs was 2.97 and 2.24-folds higher than pure MA. The results of this study suggested that SDs prepared using hot-melt extrusion technology are capable to enhance palatability, anti-inflammatory efficacy, and oral bioavailability of MA in comparison with pure drug.