Comparing the Greenness and Validation Metrics of Traditional and Eco-Friendly Stability-Indicating HPTLC Methods for Ertugliflozin Determination.

The literature does not provide any "high-performance thin-layer chromatographic (HPTLC)" techniques for the determination of a novel antidiabetic medicine, ertugliflozin (ERZ). Additionally, there are not many environmentally friendly analytical methods for ERZ measurement in the literature. A rapid, sensitive, and eco-friendly reversed-phase-HPTLC (RP-HPTLC) method was designed and validated in an attempt to analyze ERZ in marketed pharmaceutical tablets more precisely, accurately, and sustainably over the traditional normal-phase HPTLC (NP-HPTLC) method. The stationary phases used in the NP- and RP-HPTLC procedures were silica gel 60 NP-18F254S and 60 RP-18F254S plates, respectively. For NP-HPTLC, a chloroform/methanol (85:15 v/v) mobile phase was used. However, ethanol-water (80:20 v/v) was the preferred method for RP-HPTLC. Four distinct methodologies, including the National Environmental Method Index (NEMI), Analytical Eco-Scale (AES), ChlorTox, and Analytical GREEnness (AGREE) approaches, were used to evaluate the greenness of both procedures. For both approaches, ERZ detection was carried out at 199 nm. Using the NP- and RP-HPTLC techniques, the ERZ measurement was linear in the 50-600 and 25-1200 ng/band ranges. The RP-HPTLC method was found to be more robust, accurate, precise, linear, sensitive, and eco-friendly compared to the NP-HPTLC approach. The results of four greenness tools demonstrated that the RP strategy was greener than the NP strategy and all other reported HPLC techniques. The fact that both techniques can assess ERZ when its degradation products are present implies that they both have characteristics that point to stability-indicating features. 87.41 and 99.28%, respectively, were the assay results for ERZ in commercial tablets when utilizing the NP and RP procedures. Based on several validation and greenness metrics, it was determined that the RP-HPTLC approach was better than the NP-HPTLC method. As a result, it is possible to determine ERZ in pharmaceutical products using the RP-HPTLC approach.

Exploring the Potential Biological Activities of Pyrazole-Based Schiff Bases as Anti-Diabetic, Anti-Alzheimer's, Anti-Inflammatory, and Cytotoxic Agents: In Vitro Studies with Computational Predictions.

In this innovative research, we aim to reveal pyrazole-based Schiff bases as new multi-target agents. In this context, we re-synthesized three sets of pyrazole-based Schiff bases, 5a-f, 6a-f, and 7a-f, to evaluate their biological applications. The data from in vitro biological assays (including antioxidant and scavenging activities, anti-diabetes, anti-Alzheimer's, and anti-inflammatory properties) of the pyrazole-based Schiff bases 5a-f, 6a-f, and 7a-f showed that the six pyrazole-based Schiff bases 5a, 5d, 5e, 5f, 7a, and 7f possess the highest biological properties among the compounds evaluated. The cytotoxicity against lung (A549) and colon (Caco-2) human cancer types, as well as normal lung (WI-38) cell lines, was evaluated. The data from the cytotoxicity investigation demonstrated that the three Schiff bases 5d, 5e, and 7a are active against lung (A549) cells, while the two Schiff bases 5e and 7a exhibited the highest cytotoxicity towards colon (Caco-2) cells. Additionally, the enzymatic activities against caspase-3 and Bcl-2 of the six pyrazole-based Schiff bases 5a, 5d, 5e, 5f, 7a, and 7f were evaluated. Furthermore, we assessed the in silico absorption, distribution, metabolism, and toxicity (ADMT) properties of the more potent pyrazole-based Schiff bases. After modifying the structures of the six pyrazole-based Schiff bases, we plan to further extend the studies in the future.

Preparation and evaluation of antidiabetic activity of mangiferin-loaded solid lipid nanoparticles.

This study aimed to develop and optimize mangiferin-loaded solid lipid nanoparticles (MG-SLNs) using the microemulsion technique and ultrasonication. The MG-SLNs were composed of Labrafil M 2130 CS, MG, ethanol, Tween 80, and water. The optimized MG-SLNs exhibited a particle size of 138.37 ± 3.39 nm, polydispersity index of 0.247 ± 0.023, entrapment efficiency of 84.37 ± 2.43 %, and zeta potential of 18.87 ± 2.42 mV. Drug release studies showed a two-fold increase in the release of MG from SLNs compared to the solution. Confocal images indicated deeper permeation of MG-SLNs, highlighting their potential. Molecular docking confirmed mangiferin's inhibitory activity against α-amylase, consistent with previous findings. In vitro studies showed that MG-SLNs inhibited α-amylase activity by 55.43 ± 6.11 %, α-glucosidase activity by 68.76 ± 3.14 %, and exhibited promising antidiabetic activities. In a rat model, MG-SLNs significantly and sustainably reduced blood glucose levels for up to 12 h. Total cholesterol and triglycerides decreased, while high-density lipoprotein cholesterol increased. Both MG-SOL and MG-SLNs reduced SGOT and SGPT levels, with MG-SLNs showing a more significant reduction in SGOT compared to MG-SOL. Overall, the biochemical results indicated that both formulations improved diabetes-associated alterations. In conclusion, the study suggests that loading MG in SLNs using the newly developed approach could be an efficient oral treatment for diabetes, offering sustained blood glucose reduction and positive effects on lipid profiles and liver enzymes.

In-silico evaluation of Bismurrayaquinone-A phytochemical as a potential multifunctional inhibitor targeting dihydrofolate reductase: implications for anticancer and antibacterial drug development.

Dihydrofolate reductase (DHFR) has gained significant attention in drug development, primarily due to marked distinctions in its active site among different species. DHFR plays a crucial role in both DNA and amino acid metabolism by facilitating the transfer of monocarbon residues through tetrahydrofolate, which is vital for nucleotide and amino acid synthesis. This considers its potential as a promising target for therapeutic interventions. In this study, our focus was on conducting a virtual screening of phytoconstituents from the IMPPAT2.0 database to identify potential inhibitors of DHFR. The initial criterion involved assessing the binding energy of molecules against DHFR and we screened top 20 compounds ranging energy -13.5 to -11.4 (kcal/Mol) while Pemetrexed disodium bound with less energy -10.2 (kcal/Mol), followed by an analysis of their interactions to identify more effective hits. We prioritized IMPHY007679 (Bismurrayaquinone-A), which displayed a high binding affinity and crucial interaction with DHFR. We also evaluated the drug-like properties and biological activity of IMPHY007679. Furthermore, MD simulation was done, RMSD, RMSF, Rg, SASA, PCA and FEL explore the time-evolution impact of IMPHY007679 comparing it with a reference drug, Pemetrexed disodium. Collectively, our findings suggest that IMPHY007679 recommend further investigation in both in vitro and in vivo settings for its potential in developing anticancer and antibacterial therapies. This compound holds promise as a valuable candidate for advancing drug research and treatment strategies.Communicated by Ramaswamy H. Sarma.

Targeting CDK6 in hormone receptor-positive breast cancer: inhibitor discovery for precision oncology through dynamics study.

CDK6 is a critical protein involved in the regulation of the cell cycle, playing an important role in the progression from the G1 to S phase. In breast cancer, dysregulation of this protein is involved in tumour development and progression, particularly in hormone receptor-positive (HR+) breast cancers. The upregulation of CDK6 have been observed in a subset of breast cancers, leading to uncontrolled progression of the cell cycle and increased proliferation of cells. The purpose of this abstract is to provide an outline of CDK6's role. In breast cancer and the therapeutic strategies targeting CDK6 using specific selected inhibitors. To discover viable therapeutic candidates after competitive inhibition of CDK6 with a small molecular drug complex, high throughput screening and docking studies were used. Further, we carried the compounds based on ADMET properties and prediction of activity spectra for substances analysis. Finally, two different compounds were selected to carry out MD simulations. CDK6-IMPHY002642 and CDK6-IMPHY005260 are the two compounds that were identified. Overall, our results suggest that the CDK6-IMPHY002642 and CDK6-IMPHY005260 complex was relatively stable during the simulation. The compounds that have been found can also be further examined as potential therapeutic possibilities. The combined findings suggest that CDK6, together with their genetic changes, can be investigated in therapeutic interventions for precision oncology, leveraging early diagnostics and target-driven therapy.Communicated by Ramaswamy H. Sarma.

Eco-Friendly High-Performance Thin-Layer Chromatography Method for the Determination of Tenoxicam in Commercial Formulations.

There is a dearth of information in the literature regarding environmentally benign high-performance thin-layer chromatography (HPTLC) methods to determine tenoxicam (TNX). Therefore, designing and validating an HPTLC method to detect TNX in commercial tablets and capsules was the goal of this investigation. The green mobile phase utilized was the combination of ethanol/water/ammonia solution (50:45:5 v/v/v). The TNX was quantified at a wavelength of 375 nm. The proposed method's greenness profile was established using the Analytical GREEnness (AGREE) approach. The proposed methodology for determining TNX was linear in the range of 25-1400 ng/band. The proposed methodology for measuring TNX was accurate (% recoveries = 98.24-101.48), precise (% RSD = 0.87-1.02), robust (% RSD = 0.87-0.94), sensitive (LOD = 0.98 ng/band and LOQ = 2.94 ng/band), and environmentally friendly. The AGREE scale for the present methodology was derived to be 0.75, indicating an outstanding greenness profile. TNX was found to be highly stable under acidic, base, and thermal stress conditions. However, it completely decomposed under oxidative stress conditions. Commercial tablets and capsules were found to have 98.46 and 101.24% TNX, respectively. This finding supports the validity of the current methodology for measuring TNX in commercial formulations. The outcomes of this work showed that the proposed eco-friendly HPTLC methodology can be used for the routine analysis of TNX in commercial formulations.

Quantification of Suvorexant in Human Urine Using a Validated HPTLC Bioanalytical Method.

Suvorexant (SUV) is a new sedative/hypnotic medicine that is recommended to treat insomnia. It is an important medicine from a forensic point of view due to its sedative/hypnotic and depressant effects. To the best of our knowledge, high-performance thin-layer chromatography (HPTLC) bioanalytical methods have not been published to measure SUV in human urine and pharmaceutical samples. Accordingly, this study was designed and validated a sensitive and rapid bioanalytical HPTLC method to determine SUV in human urine samples for the very first time. The densitometric measurement of SUV and the internal standard (IS; sildenafil) was performed on glass-coated silica gel normal-phase-60F254S TLC plates using a mixture of chloroform and methanol (97.5:2.5 v/v) as the eluent system. Both the SUV and IS were detected at a wavelength of 254 nm. Both analytes were extracted using the protein precipitation technique utilizing methanol as the solvent. For the IS and SUV, the Rf values were 0.09 and 0.45, respectively. The proposed bioanalytical method for SUV was linear in the 50-1600 ng/band range. The current bioanalytical technique was linear, precise (% RSD = 3.28-4.20), accurate (% recovery = 97.58-103.80), robust (% recovery = 95.31-102.34 and % RSD = 2.81-3.15), rapid, and sensitive (LOD = 3.73 ng/band and LOQ = 11.20 ng/band). These findings suggested that the current bioanalytical method can be regularly used to determine SUV in wide varieties of urine samples.

Effects of Tiliroside and Lisuride Co-Treatment on the PI3K/Akt Signal Pathway: Modulating Neuroinflammation and Apoptosis in Parkinson's Disease.

Researchers are actively exploring potential bioactive compounds to enhance the effectiveness of Lisuride (Lis) in treating Parkinson's disease (PD) over the long term, aiming to mitigate the serious side effects associated with its extended use. A recent study found that combining the dietary flavonoid Tiliroside (Til) with Lis has potential anti-Parkinson's benefits. The study showed significant improvements in PD symptoms induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) when Til and Lis were given together, based on various behavioral tests. This combined treatment significantly improved motor function and protected dopaminergic neurons in rats with PD induced by MPTP. It also activated important molecular pathways related to cell survival and apoptosis control, as indicated by the increased pAkt/Akt ratio. Til and Lis together increased B-cell lymphoma 2 (Bcl-2), decreased caspase 3 activity, and prevented brain cell decay. Co-administration also reduced tumor necrosis factor alpha (TNF-α) and Interleukin-1 (IL-1). Antioxidant markers such as superoxide dismutase (SOD), catalase, and reduced glutathione significantly improved compared to the MPTP-induced control group. This study shows that using Til and Lis together effectively treats MPTP-induced PD in rats, yielding results comparable to an 8 mg/kg dose of levodopa, highlighting their potential as promising Parkinson's treatments.

Quantification of Pomalidomide Using Conventional and Eco-Friendly Stability-Indicating HPTLC Assays: A Contrast of Validation Parameters.

High-performance thin-layer chromatographic (HPTLC) assays for pomalidomide (PMD) measurement are lacking in the published database. Furthermore, eco-friendly stability-indicating analytical assays for PMD measurement are also lacking in the published database. In order to detect PMD in commercial products more accurately and sustainably than the conventional normal-phase HPTLC (NP-HPTLC) assay, an effort was made to design and verify a sensitive and eco-friendly reversed-phase HPTLC (RP-HPTLC) assay. The silica gel 60 NP-18F254S and 60 RP-18F254S plates were used as the stationary phases for NP-HPTLC and RP-HPTLC methods, respectively. The solvent system for NP-HPTLC was chloroform-methanol (90:10 v/v). However, the solvent system for RP-HPTLC was ethanol-water (75:25 v/v). The greenness scores for both assays were measured by AGREE approach. PMD measurement was performed for both assays at 372 nm. In the 50-600 and 20-1000 ng/band ranges, the NP-HPTLC and RP-HPTLC methods were linear for PMD measurement. The RP-HPTLC assay was superior to the NP-HPTLC method for measuring PMD in terms of sensitivity, accuracy, precision, and robustness. The ability of both methods to identify PMD in the presence of its degradation products suggests that both methods have stability-indicating features. When employing the NP-HPTLC and RP-HPTLC assays, respectively, the assay for PMD in commercial capsules was 88.68 and 98.83%. The AGREE scores for NP-HPTLC and RP-HPTLC assays were calculated to be 0.44 and 0.82, respectively, suggesting an outstanding greenness characteristic of the RP-HPTLC method than the NP-HPTLC method. The RP-HPTLC method was found to be superior to the NP-HPTLC method based on these findings. Therefore, the RP-HPTLC method could be successfully applied for the determination of PMD in pharmaceutical products.

Gallic-Acid-Loaded PLGA Nanoparticles: A Promising Transdermal Drug Delivery System with Antioxidant and Antimicrobial Agents.

The objective of this study was to develop an innovative gallic-acid (GA) drug delivery system that could be administered transdermally, resulting in enhanced therapeutic benefits and minimal negative consequences. The method employed involved the preparation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with GA through nanoprecipitation-denoted GA@PLGANPs. The results reveal that this strategy led to perfectly spherical, homogeneous, and negatively charged particles, which are suitable for administration via skin patches or ointments. A further analysis indicates that these GA@PLGANPs exhibit remarkable antioxidant activity as well as potent antibacterial effects against a diverse range of microorganisms, making them ideal candidates for numerous applications. Additionally, it has been observed that these nanoparticles can effectively mitigate oxidative stress while also significantly inhibiting microbial growth by exerting detrimental effects on bacterial cell walls or membranes. In conclusion, on the basis of the findings presented in this study, there is strong evidence supporting the potential use of GA@PLGANPs as an effective therapy option with reduced side effects compared to conventional drug delivery methods.

Synergistic Combination of Letrozole and Berberine in Ascorbic Acid-Stabilized AuNPs: A Promising Solution for Breast Cancer.

Breast cancer is a deadly disease that affects countless women worldwide. The most conventional treatments for breast cancer, such as the administration of anticancer medications such as letrozole (LTZ), pose significant barriers due to the non-selective delivery and low bioavailability of cytotoxic drugs leading to serious adverse effects and multidrug resistance (MDR). Addressing these obstacles requires an innovative approach, and we propose a combined strategy that synergistically incorporates LTZ with berberine (BBR) into stabilised AuNPs coated with ascorbic acid (AA), known as LTZ-BBR@AA-AuNPs. The LTZ-BBR@AA-AuNPs, a novel combined drug delivery system, were carefully designed to maximise the entrapment of both LTZ and BBR. The resulting spherical nanoparticles exhibited remarkable efficiency in trapping these two compounds, with rates of 58% and 54%, respectively. In particular, the average hydrodynamic diameter of these nanoparticles was determined to be 81.23 ± 4.0 nm with a PDI value of only 0.286, indicating excellent uniformity between them. Furthermore, their zeta potential was observed to be -14.5 mV, suggesting high stability even under physiological conditions. The release profiles showed that after being incubated for about 24 h at pH levels ranging from acidic (pH = 5) to basic (pH = 7), the percentage released for both drugs ranged from 56-72%. This sustained and controlled drug release can reduce any negative side effects while improving therapeutic efficacy when administered directly to cancer. MDA-MB-231 cells treated with LTZ-BBR@AA-AuNPs for 48 h exhibited IC50 values of 2.04 ± 0.011 µg/mL, indicating potent cytotoxicity against cells. Furthermore, the nanoparticles demonstrated excellent stability throughout the duration of the treatment.

Beta Caryophyllene-Loaded Nanostructured Lipid Carriers for Topical Management of Skin Disorders: Statistical Optimization, In Vitro and Dermatokinetic Evaluation.

This work aimed to overcome the disadvantages of the oral administration of beta-caryophyllene and boost efficiency by developing a nanostructured lipid carrier for topical administration of the drug in skin disorders. The heat emulsification method was utilized to produce beta-caryophyllene-loaded nanostructured lipid carriers. The newly created formulation was examined for its particle size, entrapment efficiency, and zeta potential after being improved using the Box-Behnken Design. The chosen formulation underwent tests to determine its ex vivo skin retention, dermatokinetic, in vitro release, antioxidant, and confocal laser scanning microscopy study. The findings of the characterization of the nanostructured lipid carriers demonstrated that the particles had a spherical form and a size of 210.86 nm (0.263 polydispersity index). The entrapment efficiency was determined to be 86.74%, and the zeta potential was measured to be -26.97 mV. The in vitro release investigation showed that nanostructure lipid carriers were capable of releasing regulated amounts of beta-caryophyllene for up to 24 hrs. In comparison to the traditional gel formulation, the ex vivo investigation demonstrated a 1.94-fold increase in the skin's capacity to retain the substance. According to the findings of the study, nanostructure lipid carriers loaded with beta-caryophyllene have the potential to be investigated for use as a topical administration method in skin disorders with enhanced skin retention and effectiveness.

A Rapid and Sensitive Stability-Indicating Eco-Friendly HPTLC Assay for Fluorescence Detection of Ergotamine.

Eco-friendly liquid chromatographic methods for measuring ergotamine (EGT) are scant in the published database. Accordingly, the goal of the current study was to develop a high-performance thin-layer chromatography (HPTLC) method for fluorescence detection of EGT in commercially available tablets. This approach was based on the application of ethyl alcohol-water (80:20 v/v) as the eco-friendly eluent mixture. The fluorescence detection of EGT was carried out at 322 nm. The greenness score of the present approach was evaluated by "Analytical GREENness (AGREE)" technology. The present approach for measuring EGT in the 25-1000 ng band-1 range was linear. The present assay for fluorescence detection of EGT was validated successfully by ICH guidelines for various parameters. The method was found to be rapid, sensitive, eco-friendly, and stability-indicating. The computed AGREE index for the current strategy was 0.84, displaying outstanding greenness features. The present methodology successfully separated the EGT degradation products under forced-degradation circumstances, exhibiting its stability-indicating qualities and selectivity. An amount of 99.33% of EGT was found in commercial formulations, indicating the validity of the current method for pharmaceutical analysis of EGT in commercial products. The results showed that EGT in commercial products might be regularly measured by the existing method.

QbD-Optimized, Phospholipid-Based Elastic Nanovesicles for the Effective Delivery of 6-Gingerol: A Promising Topical Option for Pain-Related Disorders.

In this study, elastic nanovesicles, constructed of phospholipids optimized by Quality by Design (QbD), release 6-gingerol (6-G), a natural chemical that may alleviate osteoporosis and musculoskeletal-related pain. A 6-gingerol-loaded transfersome (6-GTF) formulation was developed using a thin film and sonication approach. 6-GTFs were optimized using BBD. Vesicle size, PDI, zeta potential, TEM, in vitro drug release, and antioxidant activity were evaluated for the 6-GTF formulation. The optimized 6-GTF formulation had a 160.42 nm vesicle size, a 0.259 PDI, and a -32.12 mV zeta potential. TEM showed sphericity. The 6-GTF formulation's in vitro drug release was 69.21%, compared to 47.71% for the pure drug suspension. The Higuchi model best described 6-G release from transfersomes, while the Korsmeyer-Peppas model supported non-Fickian diffusion. 6-GTF had more antioxidant activity than the pure 6-G suspension. The optimized transfersome formulation was converted into a gel to improve skin retention and efficacy. The optimized gel had a spreadability of 13.46 ± 4.42 g·cm/s and an extrudability of 15.19 ± 2.01 g/cm2. The suspension gel had a 1.5 µg/cm2/h ex vivo skin penetration flux, while the 6-GTF gel had 2.71 µg/cm2/h. Rhodamine B-loaded TF gel reached deeper skin layers (25 µm) compared to the control solution in the CLSM study. The gel formulation's pH, drug concentration, and texture were assessed. This study developed QbD-optimized 6-gingerol-loaded transfersomes. 6-GTF gel improved skin absorption, drug release, and antioxidant activity. These results show that the 6-GTF gel formulation has the ability to treat pain-related illnesses effectively. Hence, this study offers a possible topical treatment for conditions connected to pain.

In Vitro and In Silico Anti-Picornavirus Triterpene Alkanoic Acid Ester from Saudi Collection of Rhazya stricta Decne.

The total alcohol extract obtained from the aerial parts of R. stricta and fractions of the liquid-liquid fractionation process were tested against picornavirus-causing foot-and-mouth disease (FMD) based on the traditional use of the plant in Saudi Arabia. The most active petroleum ether soluble fraction was subjected to chromatographic purification, and nine compounds were isolated, identified using various chemical and spectroscopic methods, and tested for their anti-viral potential. The new ester identified as α-Amyrin 3-(3'R-hydroxy)-hexadecanoate (1) was the most active compound with 51% inhibition of the viral growth and was given the name Rhazyin A. Compounds with ursane skeleton were more active than those with lupane skeleton except in the case of the acid derivatives where betulenic acid showed 26.1% inhibition against the viral growth, while ursolic acid showed only 16.6% inhibition. Moreover, molecular docking analysis using a glide extra-precision module was utilized for investigating the possible molecular interactions accounting for anti-viral activity against picornavirus of the nine isolated compounds. Molecular docking studies revealed a strong binding of the discovered hits within the active site of FMDV 3Cpro. Compound 1 showed the lowest docking score within the nine isolated compounds comparable to the two known anti-viral drugs; glycyrrhizic acid and ribavirin. The results of this research will provide lead candidates from natural origin with potential safety and efficacy compared to the synthetic ones with lower production costs for managing FMVD.

Quality-by-Design-Assisted Optimization of Carvacrol Oil-Loaded Niosomal Gel for Anti-Inflammatory Efficacy by Topical Route.

Niosomes are multilamellar vesicles that effectively transfer active ingredients into the skin's layers. To improve the active substance's penetration across the skin, these carriers are frequently utilized as topical drug delivery systems. Essential oils (EOs) have garnered significant interest in the field of research and development owing to their various pharmacological activities, cost-effectiveness, and simple manufacturing techniques. However, these ingredients undergo degradation and oxidation over time, leading to a loss of functionality. Niosome formulations have been developed to deal with these challenges. The main goal of this work was to create a niosomal gel of carvacrol oil (CVC) to improve its penetration into the skin for anti-inflammatory actions and stability. By changing the ratio of drug, cholesterol and surfactant, various formulations of CVC niosomes were formulated using Box Behnken Design (BBD). A thin-film hydration technique using a rotary evaporator was employed for the development of niosomes. Following optimization, the CVC-loaded niosomes had shown: 180.23 nm, 0.265, -31.70 mV, and 90.61% of vesicle size, PDI, zeta potential, and EE%. An in vitro study on drug release discovered the rates of drug release for CVC-Ns and CVC suspension, which were found to be 70.24 ± 1.21 and 32.87 ± 1.03, respectively. The release of CVC from niosomes best fit the Higuchi model, and the Korsmeyer-Peppas model suggests that the release of the drug followed the non-Fickian diffusion. In a dermatokinetic investigation, niosome gel significantly increased CVC transport in the skin layers when compared to CVC-conventional formulation gel (CVC-CFG). Confocal laser scanning microscopy (CLSM) of rat skin exposed to the rhodamine B-loaded niosome formulation showed a deeper penetration of 25.0 µm compared to the hydroalcoholic rhodamine B solution (5.0 µm). Additionally, the CVC-N gel antioxidant activity was higher than that of free CVC. The formulation coded F4 was selected as the optimized formulation and then gelled with carbopol to improve its topical application. Niosomal gel underwent tests for pH determination, spreadability, texture analysis, and CLSM. Our findings imply that the niosomal gel formulations could represent a potential strategy for the topical delivery of CVC in the treatment of inflammatory disease.

Development and Characterization of Methyl-Anthranilate-Loaded Silver Nanoparticles: A Phytocosmetic Sunscreen Gel for UV Protection.

Methyl anthranilate (MA) is a naturally derived compound commonly used in cosmetic products, such as skin care products, fine perfumes, etc. The goal of this research was to develop a UV-protective sunscreen gel using methyl-anthranilate-loaded silver nanoparticles (MA-AgNPs). The microwave approach was used to develop the MA-AgNPs, which were then optimized using Box-Behnken Design (BBD). Particle size (Y1) and absorbance (Y2) were chosen as the response variables, while AgNO3 (X1), methyl anthranilate concentration (X2), and microwave power (X3) were chosen as the independent variables. Additionally, the prepared AgNPs were approximated for investigations on in vitro active ingredient release, dermatokinetics, and confocal laser scanning microscopy (CLSM). The study's findings showed that the optimal MA-loaded AgNPs formulation had a particle size, polydispersity index, zeta potential, and percentage entrapment efficiency (EE) of 200 nm, 0.296 mV, -25.34 mV, and 87.88%, respectively. The image from transmission electron microscopy (TEM) demonstrated the spherical shape of the nanoparticles. According to an in vitro investigation on active ingredient release, MA-AgNPs and MA suspension released the active ingredient at rates of 81.83% and 41.62%, respectively. The developed MA-AgNPs formulation was converted into a gel by using Carbopol 934 as a gelling agent. The spreadability and extrudability of MA-AgNPs gel were found to be 16.20 and 15.190, respectively, demonstrating that the gel may spread very easily across the skin's surface. The MA-AgNPs formulation demonstrated improved antioxidant activity in comparison to pure MA. The MA-AgNPs sunscreen gel formulation displayed non-Newtonian pseudoplastic behaviour, which is typical of skin-care products, and was found to be stable during the stability studies. The sun protection factor (SPF) value of MA-AgNPG was found to be 35.75. In contrast to the hydroalcoholic Rhodamine B solution (5.0 µm), the CLSM of rat skin treated with the Rhodamine B-loaded AgNPs formulation showed a deeper penetration of 35.0 µm, indicating the AgNPs formulation was able to pass the barrier and reach the skin's deeper layers for more efficient delivery of the active ingredient. This can help with skin conditions where deeper penetration is necessary for efficacy. Overall, the results indicated that the BBD-optimized MA-AgNPs provided some of the most important benefits over conventional MA formulations for the topical delivery of methyl anthranilate.

Antihyperglycemic Potential of Spondias mangifera Fruits via Inhibition of 11ß-HSD Type 1 Enzyme: In Silico and In Vivo Approach.

The 11 ß- hydroxysteroid dehydrogenase 1 (11 ß-HSD1) is hypothesized to play a role in the pathogenesis of type 2 diabetes and its related complications. Because high glucocorticoid levels are a risk factor for metabolic disorders, 11ß-HSD1 might be a viable therapeutic target. In this investigation, docking experiments were performed on the main constituents of Spondias mangifera (SM) oleanolic acid, ß-amyrin, and ß-sitosterol to ascertain their affinity and binding interaction in the human 11ß-hydroxysteroid dehydrogenase-1 enzyme's active region. The results of in vitro 11ß HSD1 inhibitory assay demonstrated that the extract of S. mangifera had a significant (p < 0.05) decrease in the 11-HSD1% inhibition (63.97%) in comparison to STZ (31.79%). Additionally, a non-insulin-dependent diabetic mice model was used to examine the sub-acute anti-hyperlipidemic and anti-diabetic effects of SM fruits. Results revealed that, in comparison to the diabetic control group, SM fruit extract (SMFE) extract at doses of 200 and 400 mg/kg body weight considerably (p < 0.05 and p < 0.01) lowered blood glucose levels at 21 and 28 days, as well as significantly decreased total cholesterol (TC) and triglycerides (TG) and enhanced the levels of high-density lipoprotein (HDL). After 120 and 180 s of receiving 200 and 400 mg/kg SMFE, respectively, disease control mice showed significantly poorer blood glucose tolerance (p < 0.05 and p < 0.01). SMFE extract 200 (p < 0.05), SMFE extract 400 (p < 0.01), and Glibenclamide at a dosage of 5 mg/kg body weight all resulted in statistically significant weight increase (p < 0.01) when compared to the diabetic control group after 28 days of treatment. According to in silico, in vitro, and in vivo validation, SMFE is a prospective medication with anti-diabetic and hypoglycemic effects.

Caraway Nanoemulsion Gel: A Potential Antibacterial Treatment against Escherichia coli and Staphylococcus aureus.

Novel antibiotics are needed due to the rise of antibiotic-resistant pathogens. Traditional antibiotics are ineffective due to antibiotic-resistant microorganisms, and finding alternative therapies is expensive. Hence, plant-derived caraway (Carum carvi) essential oils and antibacterial compounds have been selected as alternatives. In this, caraway essential oil as an antibacterial treatment was investigated using a nanoemulsion gel. Using the emulsification technique, a nanoemulsion gel was developed and characterized in terms of particle size, polydispersity index, pH, and viscosity. The results showed that the nanoemulsion had a mean particle size of 137 nm and an encapsulation efficiency of 92%. Afterward, the nanoemulsion gel was incorporated into the carbopol gel and was found to be transparent and uniform. The gel had in vitro cell viability and antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The gel safely delivered a transdermal drug with a cell survival rate of over 90%. With a minimal inhibitor concentration (MIC) of 0.78 mg/mL and 0.78 mg/mL, respectively, the gel demonstrated substantial inhibition for E. coli and S. aureus. Lastly, the study demonstrated that caraway essential oil nanoemulsion gels can be efficient in treating E. coli and S. aureus, laying the groundwork for the use of caraway essential oil as an alternative to synthetic antibiotics in the treatment of bacterial infections.

Development and Evaluation of Novel Encapsulated Isoeugenol-Liposomal Gel Carrier System for Methicillin-Resistant Staphylococcus aureus.

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) bacteria have seriously threatened the health and safety of the world's population. This challenge demands the development of alternative therapies based on plant origin. This molecular docking study ascertained the orientation and intermolecular interactions of isoeugenol within penicillin-binding protein 2a. In this present work, isoeugenol as an anti-MRSA therapy was selected by encapsulating it into a liposomal carrier system. After encapsulation into the liposomal carrier, it was evaluated for encapsulation efficiency (%), particle size, zeta potential, and morphology. The percentage entrapment efficiency (% EE) was observed to be 57.8 ± 2.89% with a particle size of 143.31 ± 7.165 nm, a zeta potential of (-)25 mV, and morphology was found to be spherical and smooth. After this evaluation, it was incorporated into a 0.5% Carbopol gel for a smooth and uniform distribution on the skin. Notably, the isoeugenol-liposomal gel was smooth on the surface with a pH of 6.4, suitable viscosity, and spreadability. Interestingly, the developed isoeugenol-liposomal gel was safe for human use, with more than 80% cell viability. The in vitro drug release study shows promising results with 75.95 ± 3.79% of drug release after 24 h. The minimum inhibitory concentration (MIC) was 8.236 µg/mL. Based on this, it can be concluded that encapsulating isoeugenol into the liposomal gel is a potential carrier for MRSA treatment.