Design and evaluation of sulfadiazine derivatives as potent dual inhibitors of EGFRWT and EGFRT790M: integrating biological, molecular docking, and ADMET analysis.

A series of derivatives (5-14) were synthesized through the diazotization of sulfadiazine with active methylene compounds. The chemical structures of these newly designed compounds were validated through spectral and elemental analysis techniques. The antiproliferative potential of derivatives 5-14 was assessed against three distinct cancer cell lines (A431, A549, and H1975) using the MTT assay. The results revealed that compounds 8, 12, and 14 exhibited the most potent antiproliferative activity, with IC50 values ranging from 2.31 to 7.56 µM. Notably, these values were significantly lower than those of known EGFR inhibitors, including erlotinib, gefitinib, and osimertinib, suggesting the potential of these derivatives as novel antiproliferative agents. Furthermore, compound 12 was identified as the most potent inhibitor of both EGFRWT and EGFRT790M protein kinases, with IC50 values of 14.5 and 35.4 nM, respectively. These results outperformed those of gefitinib and osimertinib, which exhibited IC50 values of 18.2 and 368.2 nM, and 57.8 and 8.5 nM, respectively. Molecular docking studies of compounds 8, 12, and 14 within the ATP-binding sites of both EGFRWT and EGFRT790M corroborated the in vitro results when compared to erlotinib, gefitinib, and osimertinib. The docking results indicated that compound 8 exhibited a favorable binding affinity for both EGFRWT and EGFRT790M, with binding scores of -6.40 kcal mol-1 and -7.53 kcal mol-1, respectively, which were comparable to those of gefitinib and osimertinib, with binding scores of -8.01 and -8.72 kcal mol-1, respectively. Furthermore, an assessment of the most promising EGFR inhibitors (8, 12, and 14) using the egg-boiled method for their in silico ADME properties revealed significant lipophilicity, blood-brain barrier (BBB) penetration, and gastrointestinal (GIT) absorption. Collectively, our designed analogs, particularly compounds 8, 12, and 14, exhibit promising dual antiproliferative and EGFRWT and EGFRT790M kinase inhibitory properties, positioning them as efficient candidates for further therapeutic development.

Design and synthesis of high quantum yield doped carbon nano probe derived from household sources for sensing of the anti-GERD drug pantoprazole.

This contribution aims to design and validate a new green, cheap, and fast approach for determining the anti-GERD drug pantoprazole in different matrices. New S and N-doped carbon nanomaterials (S,N-CNMs) have been prepared via microwave irradiation of a mixture of widely available household sources. Remarkably, the utilization of a blend of carbamide and thiocarbamide with table sugar yields S,N-CNMs exhibiting the utmost quantum yield (54 %), hydrophilicity, as well as stable, homogeneous, and diminutive particle size distribution. Fourier transform infrared spectroscopy, transmission electron microscopy, spectrophotometry, and fluorescence spectroscopy were applied to characterize the S,N-CNMs. The S,N-CNMs have been used as a turn-off fluorescence probe to determine pantoprazole via a synergism of the inner filter effect and static quenching mechanisms. The fluorescence quenching is linearly correlated to pantoprazole concentration over the range of 1.0-25.0 µg/mL with a detection limit of 0.16 µg/mL. The developed probe exhibited good selectivity for pantoprazole in the presence of variability of substances. Therefore, it was applied for quality control of pantoprazole in pharmaceutical tablets and vials with an average recovery % of 100.10 ± 0.77 % and 100.33 ± 0.92 %, respectively. Moreover, it was successfully implemented to examine the content uniformity of pantoprazole in tablets. Furthermore, the prepared S,N-CNMs have been successfully used for the analysis of pantoprazole in human plasma after a simple protein precipitation step with a recovery % of 97.88 ± 5.72 %. The greenness and blueness of the developed method have been positively assessed by recent tools showing the eco-friendliness and applicability of the developed method.

Efficient application of Pyrosin B for nano-gram level assay of antiparkinsonian medication, rasagiline: Evaluation of tablets and content uniformity.

Rasagiline (RAS) is a medication for Parkinson's disease that increases dopamine levels in the brain by inhibiting monoamine oxidase, helping to alleviate symptoms. The proposed study aims to develop an efficient, feasible, and sensitive method for RAS assay, utilizing Pyrosin B dye, a convenient fluorescent ligand. Combining the RAS analyte with Pyrosin B ligand in a mildly acidic buffered solution rapidly quenches the native fluorescence of the ligand. This quenching results from the formation of a specific ion-dipole association complex between the lone pair-bearing atoms of the ligand and the protonated amine moiety of RAS, highlighting their interactive chemistry under these conditions. The degree of this interaction demonstrated superior sensitivity compared with reported alternatives, exhibiting a linear range of 50.0 to 1000.0 ng/mL. The method is characterized by a limit of detection (LOD) of 16.0 ng/mL and a limit of quantification (LOQ) of 48.0 ng/mL. By optimizing the RAS-Pyrosin B system, the variable parameters were finely tuned, ensuring the assay method's reliability. The method's accuracy, precision, selectivity, and robustness were validated according to International Council for Harmonization (ICH) guidelines, enabling precise and efficient analysis of RAS in the nanogram range. This method streamlines the analysis procedure and reduces environmental impact, making it a promising approach for the quality control of ParkintreatR tablets (1 mg) and other analytical applications.

Facile Integration of Hanztsch's Switch-Off/On Modeled Fluorogenic Probe for Feasible Tagging and Tracking of the Midodrine Drug in Different Matrices; First Evaluation of the Method's Greenness, Whiteness, Blueness, Quantum Yield, and Tablets' Content Homogeneity.

The proposed investigation follows a certain methodology to guarantee that the procedure employed is sustainable and green. It is noteworthy to mention that various tools have been implemented as potential indicators of environmental sustainability (greenness and whiteness). From a novelty viewpoint, a new tool, BAGI, for the method's blueness evaluation was applied to the planned method and showed a high applicability score. Fortunately, the WAC concept, which combines ecological and functional variables using the Green/Red/Blue design (RBG 12 tool), identifies the established analytical approach as white. In the planned study, a new, green, simple, nano-trace-sensitive, original fluorimetric methodology was established to analyze and assess midodrine hydrochloride content in different matrices. Midodrine's primary amine moiety reacts with Diacetylmethane/Oxymethylene reagent in an acetate buffer, which leads to generating a fluorescent dihydrolutidine derivative (Hantzsch-named reaction). Consequently, the signal strength of this compound was quantified at 487 nm, with an excitation wavelength of 426 nm. This analysis indicated that the technique exhibited linearity within the range of 0.05 to 1.1 µg mL-1 concentrations, accompanied by remarkably good sensitivity values (LOD and LOQ). The methodology employed in this examination was subjected to validation following the rules recognized by ICH. From the perspective of pharmacy and chemistry, the method presented in this study was successfully employed to analyze commercially available tablets, oral drops, and human fluids. The outcomes obtained demonstrated satisfactory recovery rates without any interference from excipients. Following the USP recommendations, the intended technique was finally implemented to explore the content homogeneity evaluation.

Formulation and Evaluation of Meloxicam Hybrid nano Particles.

The goal of the present study was to prepare meloxicam (MX) entrapped hybrid particles (HPs) to enhance intestinal permeation and anti-inflammatory activity. MX-HPs were prepared by nanoprecipitation method using lipid, chitosan, poloxamer, and TPGS. The formulations (MX-HPs1, MX-HPs2, MX-HPs3) were evaluated for particle size, entrapment efficiency, and drug release to select the optimized composition and further evaluated for permeation study, stability study, morphology, interaction study, and anti-inflammatory activity by carrageenan-induced rat paw edema test. The prepared MX-HPs showed nano sized particles (198.5 ± 3.7 to 223.8 ± 2.1 nm) and PDI (<0.3), zeta potential (16.5 ± 2.7 to 29.1 ± 3.6 mV), and high entrapment efficiency (75.1 ± 4.7 to 88.5 ± 3.9%). The surface morphology was assessed by transmission electron microscopy and showed non-aggregated particles. Infra-red (IR) spectroscopy of pure MX as well as formulation revealed no drug-polymer interaction and X-ray diffraction confirmed the conversion of crystalline MX into amorphous form. The release study data revealed prolonged MX release for 24 h. The selected optimized hybrid particles (MX-HPs2) revealed a 2.3-fold improved enhancement ratio than free MX. The storage stability and gastrointestinal stability data demonstrated a stable formulation in SIF as well as SGF. The anti-inflammatory activity showed better therapeutic action than pure MX dispersion. From the study, it can be concluded that the prepared MX-HPs may be a promising delivery system for MX in treating inflammatory disorders.

Dual benefits of NBD-Cl fluorogenic action and sample pretreatment (SALLE) technology in the assessment of anticoagulant medication: Dabigatran in pharmaceutical capsules and plasma samples.

Dabigatran (DBG), marketed as Pradaxa, is an anticoagulant medication prescribed for the treatment and mitigation of blood clots and to lower the risk of stroke in individuals with the heart condition known as atrial fibrillation. This medication is specifically indicated for preventing blood clots post hip or knee replacement surgeries and in patients with a prior history of clots. Compared to warfarin, dabigatran serves as a viable alternative that does not necessitate routine blood monitoring tests. The complimentary benefits associated with SALL (salting-out assisted liquid-liquid extraction) and the fluorogenic capabilities of benzofurazan. These methods were combined to provide an affordable and sensitive DBG assaying method. The spectral strength of the yellow luminous product was examined at 533.8 nm and by adjustment of a wavelength of 474.7 nm for excitation. To assess its linearity, the calibration chart was tested across a DBG concentration range of 30-500 ng/ml. Via accurate computation based on ICH, the detection limit (LD) was determined to be 9.5 ng/ml, and the strategy can quantify the DBG to a limit of 28 ng/ml. To ensure success, various crucial parameters for method implementation have been extensively studied and adapted. The validation of the strategy adhered to the policies outlined by ICH, affirming its precision in quantifying DBG in capsules. Furthermore, the inclusion of SALLE steps facilitated accurate monitoring of DBG in plasma samples, introducing a unique and advanced methodology for analyzing this compound in biological samples.

A highly sensitive first derivative synchronous spectrofluorimetric approach for the simultaneous analysis of the anti-breast cancer co-administered drugs, letrozole and tramadol in dosage forms and human plasma at nanogram levels.

Letrozole is an anticancer medication prescribed for the management of estrogen receptor-positive breast cancer in postmenopausal women. Chronic pain is prevalent in patients receiving chemotherapy, leading to the use of adjuvant analgesics such as tramadol. This work introduces the first analytical approach for the concurrent quantification of letrozole and tramadol, two co-administered drugs, employing a rapid, highly sensitive, eco-friendly, and cost-effective first derivative synchronous spectrofluorimetric technique. The fluorescence of tramadol and letrozole was measured at wavelengths of 235.9 nm and 241.9 nm, respectively using a wavelength difference (Δλ) of 60.0 nm. The developed approach demonstrated exceptional linearity (r ˃ 0.999) within the specified concentration ranges for tramadol (10.0-1200.0 ng/mL) and letrozole (1.0-140.0 ng/mL). The results demonstrated that the proposed technique exhibits a high level of sensitivity, with detection limits of 0.569 and 0.143 ng/mL for tramadol and letrozole, respectively, indicating the good bioanalytical applicability. The within-run precisions, both intra-day and inter-day, for both analytes, were less than 0.71 % RSD. The developed approach was effectively applied to simultaneously estimate the mentioned drugs in their tablets and human plasma samples, achieving high percentage recoveries and low % RSD values. In order to assess the environmental sustainability of the developed approach, Analytical GREEnnessNNESS (AGREE) and the Green Analytical Procedure Index (GAPI) metric tools were employed. Both tools revealed that the developed approach is excellent green, suggesting its usage as an environmentally-friendly alternative for the routine assayof the investigated pharmaceuticals. The developed approach was validated according to the ICHQ2 (R1) requirements.

Formulation of silymarin surface modified vesicles: In vitro characterization to cell viability assessment.

Silymarin (SLR) is a poorly water-soluble bioactive compound with a wide range of therapeutic activities. Nanosized silymarin vesicles (F1-F6) were prepared by the solvent evaporation rehydration method. The silymarin vesicles were evaluated for vesicle size, surface charge, entrapment efficiency, and drug release studies. The optimized SLR lipid vesicle (F3) was further modified with the addition of the cationic polymer chitosan. After that, the modified vesicle (F3C1) was assessed for permeation flux, antimicrobial activity, cell viability, and molecular docking studies. The silymarin vesicles showed nanometric size (<250 nm), low polydispersibility index (<0.05), negative surface charge, and high SLR entrapment (85-95 %). The drug release study result demonstrated a maximum drug release of 91.2 ± 2.8 %. After adding chitosan to the surface, there was a significant change in the size, polydispersibility index, surface charge (positive), and encapsulation efficiency. The drug release was found to be prolonged, and the permeation flux was also increased in comparison to free SLR. A comparative antimicrobial result was observed in comparison to the free SLR and standard drug. The cell viability assay also demonstrated a low IC50 value for F3C1 against the cell line.

An ingenious technique based on the usage of fluorone-based dye; pyrosin B in prucalopride assay in different matrices through an "on-off" dye native fluorescence probe.

Prucalopride (PCD), is a modern medication approved by the United States in 2018 to alleviate constipation caused by motility issues. PCD demonstrates a strong affinity and selectivity toward the 5-HT4 receptor. The study here introduces a feasible, direct, non-extractive, and affordable pathway for PCD analytical tracking. The fluorimetric study is based on the on-off effect on the emission amplitude of fluorone-based dye (pyrosin B). In a one-pot experiment, the complex between PCD and pyrosin B is formed instantly in an acidic medium. Correlation between decreased pyrosin B emission and PCD concentrations provides a linear calibration plot from 50 to 900 ng/mL. PCD-dye complex system affecting variables were meticulously tuned. The values of the estimated limit of quantitation and limit of detection for the current methodology were 47.5 and 15.7 ng/mL, respectively. Conformity of the strategy validity was achieved by a comprehensive study of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use criteria. The method was convincingly applied for PCD assay in tablets and content uniformity investigation. Furthermore, PCD tracking in the spiked biological fluid was applied. Finally, the method uses distilled water as dispersing medium which rise accommodation with the green chemistry principle.

Facile and green chemistry-compatible fluorescence spectroscopic applications of acid red 87 used to evaluate eletriptan, antimigraine, in its pharmaceutical and biological samples.

Eletriptan (ETR), a selective pharmaceutical agent agonist of the 5-hydroxytryptamine1 receptor subtype, are primarily used to treat acute migraine attacks. ETR is a triptan-class medication that works by narrowing cerebral blood vessels and reducing chemicals that produce headache pain, light and sound sensitivity, and nausea. Due to its effectiveness in reducing migraine symptoms, it is a worthwhile choice for those looking for quick and efficient treatment. A green, raid, one-pot and straightforward fluorescence spectrometric method was employed to evaluate ETR in tablets and biological samples. By introducing the ETR drug and the fluorescent ligand, Acid red 87, in an acidic buffer, a quenching of the ligand native fluorescent was promptly produced. The quenching action was simply attributed to the selective ion-pair complex generation between the cationic target and the selected ligand. An increase in ETR concentration was linearly proportional to the quenching response in the 50.0 - 500.0 ng/mL range. The optimal configurations for adjusting the system's variable parameters were determined by examining the ETR-Acid red 87 system's response. Additionally, the sensor that was developed met the standards set by the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. The sensitivity thresholds of the approach were 13.8 and 42.0 ng/mL for the detection and quantification parameters, respectively, LOD and LOQ. This approach proficiently evaluated the pharmaceutical and biological samples of ETR. Finally, the proposed approach not only simplifies the analysis process but also limits the badimpact on the environment, making it a promising technique for analytical applications.

Integration of a facile sustainable resonance Rayleigh scattering switchable-based system for feasible determination of centrophenoxine, a nootropic and antioxidant agent; application to crude materials and dosage forms.

The proposed research adheres to a certain methodology to ensure that the technique used for analyzing the centrophenoxine drug is sustainable and green. It is important to highlight that several tools that have been recently developed were utilized as potential indicators of environmental sustainability and applicability. The present research presents a novel and entirely innovative method utilizing ultrasensitive spectrofluorimetry for the detection of centrophenoxine (CPX) drug. The employed methodology in this study involved the utilization of one-step, one-pot, and direct spectrofluorimetric technique, which was found to be both efficient and environmentally sustainable in the validation and assessment of the drug. Simply, when CPX and erythrosine B reagent were combined in an acidic environment, the highly resonance Rayleigh scattering product was immediately produced. The sensitivity limits were observed to be within the range of 15-47 ng mL-1, whereas the linearity was assessed to be in the range of 50-2000 ng mL-1. The optimal settings for all modifiable parameters of the system were ascertained through an analysis of centrophenoxine-erythrosine B complexes. Moreover, the system demonstrated compliance with International Council for Harmonization (ICH) specifications without encountering any issues. The suggested process was then rated on different recent environmental safety measuring metrics to see how good it was for the environment. Fortunately, the WAC standards that combine ecological and functional elements utilizing the Green/Red/Blue (RGB 12) design also acclaimed the current analytical technique as a white one. Additionally, a new applicability evaluation tool (BAGI) was employed to estimate the practicability of the planned method in the analytical chemistry field.

Synergistic utility of NBD-Cl fluorogenic loading activity and salting-out assisted liquid-liquid extraction as sample pretreatment in rasagiline tracking in different matrices.

A typical drug used to treat Parkinson's disease is called rasagiline. It belongs to an assortment of drugs known as monoamine oxidase inhibitors, which function by raising dopamine levels in the brain. This work created a unique spectrofluorimetric method for the analytical assay of rasagiline for the first time. The approach utilized the synergistic utility of the fluorogenic properties of benzofurazan and salting-out assisted liquid-liquid extraction. By combining these techniques an ultrasensitive, and highly selective methodology for the assay of rasagiline was established. Measurements were made of the resultant yellow fluorescent product at 533 nm by applying an excitation wavelength of 475.3 nm. The calibration graph was examined to assess its linearity across a range of 30-600 ng/ml. Through estimation, the limit of detection was discovered to be 8.9 ng/ml, while the quantitation limit was estimated to be 27 ng/ml. All relevant parameters influencing the fulfillment of the developed method were thoroughly examined and tuned. Following the directives set by the (ICH) the suggested approach was confirmed and demonstrated its capability for the accurate determination of rasagiline in tablets, as well as for testing content uniformity. The incorporation of salting-out assisted liquid-liquid extraction technology enables effective tracking of rasagiline in plasma samples, providing a novel and innovative approach for its analysis in biological matrices.

Self-assembling Organogels Loaded with Tenoxicam for Local Intensive Pain and Inflammation Cure: In Vitro and In Vivo Correlation.

Due to tenoxicam (TX)'s poor aqueous solubility (0.072 mg/ml), it is poorly absorbable in the GIT, and the long-term oral administration of TX may cause severe GIT disturbances. Topical administration of TX can help in bypassing the GIT adverse effects. Therefore, in the present work, we constructed different pluronic/lecithin organogels (PLOs) for topical delivery of TX. PLO was constructed simply via direct mixing of an aqueous pluronic solution with lecithin solution. The prepared PLO formulations were characterized for their physicochemical properties including pH, drug content, visual inspection, viscosity, and spreadability. Also, the in vitro release and kinetic studies were carried out to investigate the mechanism of drug release. Moreover, the in vivo studies were carried out by investigating the anti-inflammatory and analgesic activities using albino male rats. The results showed that the modified PLOs have good physicochemical properties. The viscosity of the modified gels is a direct proportionality with both lecithin and pluronic concentrations. Also, subsequently, the drug release rate is directly proportional to gel viscosity. Moreover, the in vivo studies showed that the modified PLOs (F19) showed a significant ( < 0.05%) paw edema inhibition and pain analgesia compared with other investigated groups. Also, the results indicated that the increase in dose is accompanied by higher activity and a longer duration of action which extended to 12 h. Hence, the modified PLOs are promising safe candidates or vehicles for effective TX loading with sustained delivery behavior.

Formulation of silymarin binary and ternary solid dispersions: Characterization, simulation study and cell viability assessment against lung cancer cell line.

Silymarin (SL) is a water-insoluble flavonoid used in the treatment of different diseases, but its therapeutic activity is limited due to its low solubility. So, in the present study, SL solid dispersions (SDs) were developed using different carriers like Kollidone VA64 (KL), Soluplus (SP), and Poloxamer 188 (PL) by solvent evaporation (SE), microwave irradiation (MI), and freeze-drying (FD) methods. The phase solubility and saturation solubility studies were assessed to estimate the stability constant as well as the carrier effect. The dissolution studies were performed for prepared SL-SDs (binary and ternary) to select the optimum SL-SDs. The selected SL-SDs (F5, F9) were further characterized for infrared spectroscopy (IR), nuclear magnetic resonance (NMR), differential scanning calorimeter (DSC), scanning electron microscope (SEM), and X-ray diffraction (XRD). Finally, the comparative cell viability assay (lung cancer cell line) was performed to evaluate the change in activity after the formulation of SDs. The phase solubility and solubility study results displayed marked enhancements in solubility. The dissolution study findings showed significant enhancement in drug release from ternary solid dispersions (F7-F9) > ternary physical mixture (PM3) > binary solid dispersions (F1-F6) > binary physical mixture (PM1, PM2) in comparison to free SL. A greater release was observed from ternary SDs due to the addition of PL in the formulation, which had a synergistic effect on increasing the solubility. IR and NMR spectra revealed no chemical interaction between SL, KL, and PL. DSC, XRD, and SEM all confirmed the transformation of crystalline SL into amorphous SL. The cell viability assay demonstrated significantly enhanced results from ternary solid dispersion (F9) compared to free SL. Based on the study results, it can be said that SL-SDs are an alternative way to deliver drugs orally that can improve solubility and have anti-cancer activity.

Utility of Cilefa Pink B, a foodstuff dye as a fluoro-substrate in the devising of the first facile green Molecular-mass-Related Fluorescence Sensor for quantifying amlodipine in batched material and dosage forms; content uniformity evaluation.

This study introduces the first and unique Molecular-mass-Related Fluorescence Sensor as the first fluorimetric strategy for determining amlodipine. An environmentally friendly, single-step, and direct spectrofluorimetric approach was utilized to evaluate the analyte. In an acidic setting, combining the amlodipine medication and the fluorescent dye Cilefa Pink B generated an instantaneous ultra-fluorescent product. An increase in dye response after adding amlodipine was proportional to the molecular weight of the generated complex, as measured at 329 nm. was the idea ofthe applied fluorimetric analysis. The complexing process increased the molecular mass from 879.86 to 1288.739 g mol-1. The medication's range of 0.050-1.00 µg mL-1 is directly correlated with this molecular massenlargement. The ideal settings for the changeable parameters of the system were established through an analysis of the response of the amlodipine-Cilefa Pink B system. Furthermore, the developed sensor complied with ICH (International Council for Harmonization) standards. The sensitivity limits were 0.0139 µg mL-1 (for the detection limit, LOD) and 0.042 µg mL-1 (for the quantification limit, LOQ). Additionally, this method effectively recovered the drug in its original and therapeutic dosage forms. Finally, the proposed process's environmental impact was also assessed through different modern greenness evaluation tools.

A highly sensitive micelle-enhanced synchronous spectrofluorimetric determination of the recently approved co-formulated drugs, bilastine and montelukast in pharmaceuticals and human plasma at nanogram levels.

In this study, the simultaneous determination of bilastine and montelukast, two recently approved co-formulated antihistaminic medications, was accomplished using a quick, sensitive, environmentally friendly, and reasonably priced synchronous fluorescence spectroscopic approach for the first time. Enhancement of the method's sensitivity down to nanogram levels was achieved by the addition of sodium dodecyl sulfate (1.0% w/v) as a micellar system. According to the results, bilastine and montelukast's fluorescence was measured at 255.3 and 355.3 nm, respectively, using Δλ of 40.0 nm and distilled water as a green diluting solvent. With respect to the concentration ranges of bilastine (5.0-300.0 ng/ml) and montelukast (50.0-1000.0 ng/ml), the method showed excellent linearity (r ≥ 0.9998). The results showed that the suggested method is highly sensitive, with detection limits of 1.42 and 13.74 ng/ml for bilastine and montelukast, respectively. Within-run precisions (intra- and interday) per cent relative standard deviations (RSD) for both analytes were <0.59%. With high percentage recoveries and low percentage RSD values, the designed approach was successfully applied for the simultaneous estimation of the cited medications in their dosage form and human plasma samples. To evaluate the green profile of the suggested method, an analytical GREENNESS metric approach (AGREE) and green analytical procedure index (GAPI) metric tools were used. These two methods for evaluating greenness confirmed that the developed method met the highest number of green requirements, recommending its use as a green substitute for the routine analysis of the studied drugs. The proposed approach was validated according to ICHQ2 (R1) guidelines.

Formulation of Silymarin-ß Cyclodextrin-TPGS Inclusion Complex: Physicochemical Characterization, Molecular Docking, and Cell Viability Assessment against Breast Cancer Cell Lines.

Silymarin (SIL) is a poorly water-soluble flavonoid reported for different pharmacological properties. Its therapeutic applications are limited due to poor water solubility. In this study, the solubility of silymarin has been enhanced by preparing freeze-dried binary and ternary complexes using beta cyclodextrin (ßCD) and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS). The stoichiometry of the drug and the carrier was selected from the phase solubility study. The dissolution study was performed to assess the effect of complexation on the release pattern of SIL. The formation of inclusion complexes was confirmed by different physicochemical studies. Finally, a cell viability assay (MCF 7; breast cancer cell line) was performed to compare the activity with free SIL. The phase solubilization results revealed the formation of a stable complex (binary) with a stability constant and complexation efficiency (CE) value of 288 mol L-1 and 0.045%. The ternary sample depicted a significantly enhanced stability constant and CE value (890 mol L-1 and 0.14%). The release study results showed a marked increase in the release pattern after addition of ßCD (alone) in the binary mixture (49.4 ± 3.1%) as well as inclusion complex (66.2 ± 3.2%) compared to free SIL (32.7 ± 1.85%). Furthermore, with the addition of TPGS in SIL-ßCD (ternary), the SIL release was found to be significantly enhanced from the SIL ternary mixture (79.2 ± 2.13%) in 120 min. However, fast SIL release was achieved with 99.2 ± 1.7% in 45 min for the SIL ternary complex. IR and NMR spectral analysis results revealed the formation of a stable complex with no drug-polymer interaction. The formation of complexes was also confirmed by the molecular docking study (docking scores of 4.1 and -6.4 kcal/mol). The in vitro cell viability result showed a concentration-dependent activity. The IC50 value of the SIL ternary complex was found to be significantly lower than that of free SIL. The findings of the study concluded that the prepared SIL inclusion complex can be used as an alternative oral delivery system to enhance solubility, dissolution, and biological activity against the tested cancer cell line.

Effect of nano-encapsulated food flavorings on streptozotocin-induced diabetic rats.

Flavors and aromas are widely used in food and pharmaceutical industries to enhance food palatability. However, it is worth noting that they may also have bioactivity. This study aims to examine the potential impact of key flavors and their nanocapsules on health and diseases, such as type 2 diabetes mellitus (T2DM). The 36 nanocapsules of key flavorings were prepared by high shear homogenization (HSH). Seventy-two male Sprague-Dawley rats received a single dosage of streptozotocin (35 mg kg-1 body weight) intraperitoneally. All of the nutritional and biochemical parameters were statistically analyzed. A virtual docking study was conducted. Linalool nanoemulsion results showed the highest encapsulation efficiency (86.76%), while isoamyl acetate nanoparticles showed the lowest (69.99%). According to GC-MS analysis, encapsulation did not affect the flavoring structure with particle size distributions ranging from 277.3 to 628.8 nm. Using TEM, nanoemulsion particles appeared spherical with a desired nanometric diameter size. In the oral glucose tolerance test, flavorings in oil and nanoforms had no discernible hypoglycemia effects in normal rats. The nutritional and biochemical parameters confirmed that both normal and nanoencapsulation forms demonstrated a potential anti-hyperglycemic effect, and enhanced the rat health compared to the raw flavorings. The studied flavorings and their nanocapsules seem to have the potential double effect of a flavor compound as a food palatability enhancer with a potential beneficial effect on type 2 diabetes mellitus without any health drawbacks.

Formulation of multicomponent inclusion complex of cyclodextrin-amino acid with Chrysin: Physicochemical characterization, cell viability and apoptosis assessment in human primary glioblastoma cell line.

Chrysin (CR) is a water-insoluble drug reported for different therapeutic effects. The microwave irradiation method was used in this study to create a multicomponent inclusion complex (CR-MC) containing CR (drug) and carrier hydroxyl propyl beta cyclodextrin (HP ß CD) and L-arginine (LA). The prepared inclusion complex (CR-MC) was evaluated for dissolution study and results were compared with chrysin physical mixture (CR-PM). Further, the samples were assessed for infra-red (IR), nuclear magnetic resonance (NMR), differential scanning calorimeter (DSC), scanning electron microscope (SEM) and molecular docking. Finally, the cell viability, reactive oxygen species and flow cytometer studies were also assessed to check the potential of the prepared inclusion complex on the human primary glioblastoma cell line (U87-MG cell). The phase solubility findings revealed a stability constant (773 mol L-1) as well as a complexation efficiency of 0.027. The dissolution study displayed a significant increase in CR release from CR-MC (99.03 ± 0.39%) > CR-PM (70.58 ± 1.16%) > pure CR (35.29 ± 1.55%). NMR and IR spectral data revealed no interaction between CR and carriers. SEM and DSC study results revealed the conversion into amorphous form. The molecular docking results illustrated a high docking score, which supports the findings of complex formation. The cell viability, reactive oxygen species, and flow cytometry studies results showed enhanced activity from CR-MC against the tested human primary glioblastoma cell line. From the results it has been observed that chrysin solubility significantly increased after complexation and there in vitro activity also enhanced against cancer cell line.

Effect of Europinidin against Alcohol-Induced Liver Damage in Rats by Inhibiting the TNF-α/TGF-ß/IFN-γ/NF-kB/Caspase-3 Signaling Pathway.

BACKGROUND: The effect of europinidin on alcoholic liver damage in rats was examined in this research. METHODS: A total of 24 Wistar rats were grouped in the same way into four groups: normal control (normal), ethanol control (EtOH), europinidin low dose (10 mg/kg), and europinidin higher dose (20 mg/kg). The test group rats were orally treated with europinidin-10 and europinidin-20 for 4 weeks, whereas 5 mL/kg distilled water was administered to control rats. In addition, 1 h after the last dose of the above-mentioned oral treatment, 5 mL/kg (i.p.) EtOH was injected to induce liver injury. After 5 h of EtOH treatment, samples of blood were withdrawn for biochemical estimations. RESULTS: Administration of europinidin at both doses restored all of the estimated serum, i.e., liver function tests (ALT, AST, ALP), biochemical test (Creatinine, albumin, BUN, direct bilirubin, and LDH), lipid assessment (TC and TG), endogenous antioxidants (GSH-Px, SOD, and CAT), malondialdehyde (MDA), nitric oxide (NO), cytokines (TGF-ß, TNF-α, IL-1ß, IL-6, IFN-γ, and IL-12), caspase-3, and nuclear factor kappa B (NF-κB) associated with the EtOH group. CONCLUSION: The results of the investigation showed that europinidin had favorable effects in rats given EtOH and may have hepatoprotective potential property.