Effective synthesis and characterization of citric acid cross-linking of modified ferrous metal-organic framework and chitosan nanocomposite sponge for Th(IV) elimination: Adsorption isotherms, kinetic analysis, and optimization by Box-Behnken design.

This research presents a novel nanocomposite of ferrous metal-organic framework (Fe(II)-MOF) that has been encapsulated with chitosan matrix, leading to the development of a new adsorbent referred to as NH2-Fe(II)-MOF@CSC composite sponge. This composite sponge has shown effectiveness in removing radioactive thorium (IV) contamination from water sources. The adsorbent underwent characterization using techniques including FTIR, PXRD, BET analysis, and SEM. The adsorbent has a high surface area of 1360.8 m2/g. The most effective conditions for adsorbing Th(IV) were found to be a pH of 5, using 0.02 g of adsorbent dose per 25 mL, and maintaining a contact time of 100 min. The composite sponge demonstrated an impressive maximum adsorption capacity of 618.8 mg/g for Th(IV). The adsorption process was fitted to Langmuir isothermally and kinetically fitted to pseudo-second-order. Nonetheless, the relatively low adsorption energy of 6.22 kJ/mol suggests that the main adsorption mechanism is physisorption, which is marked by weaker van der Waals forces. This discovery could have implications for the material's potential for easy regeneration. In the analysis of the influence of temperature on the adsorption of Th(IV), it was discovered that the adsorption process is endothermic because the positive ΔHo value was 24.48 kJ.mol-1. Furthermore, a positive ΔSo value of 87.46 J.mol-1 K-1 suggests the existence of disorder at the solid-solution interface. Conversely, a temperature rise resulted in a higher negatively charged ΔGo, indicating that the adsorption process is spontaneous. The research also examined the mechanism of interaction, such as π-π interaction, hydrogen bonding, pore filling, and electrostatic interaction. It was noted that the adsorbent can be efficiently used for a maximum of six cycles, demonstrating its economic viability. The adsorption outcomes were optimized using the Box Behnken design (BBD).

Quality by Design Approach for the Development of Cariprazine Hydrochloride Loaded Lipid-Based Formulation for Brain Delivery via Intranasal Route.

BACKGROUND: Cariprazine (CPZ) is a third-generation antipsychotic medication that has been approved for treating schizophrenia. This study aimed to develop a cariprazine-loaded nanostructured lipid carrier (CPZ-NLCs) to prevent first-pass metabolism and improve bioavailability and site-specific delivery from the nose to the brain. METHOD: The CPZ-NLCs were prepared using melt emulsification. The formulation was optimized using the Box-Behnken design (BBD); where the influence of independent variables on critical quality attributes, such as particle size and entrapment efficiency, was studied. RESULT: The optimized batch (F6) had a particle size of 173.3 ± 0.6 nm and an entrapment efficiency of 96.1 ± 0.57%, respectively. The in vitro release showed >96% release of CPZ from NLC within 30 min. The optimized formulation's ex vivo studies revealed significantly increased CPZ permeability (>75%) in sheep nasal mucosa compared to the CPZ suspension (~26%). The ciliotoxicity study of the nasal mucosa revealed that the CPZ-NLC formulation did not affect the nasal epithelium. The intranasal administration of the formulation achieved 76.14±6.23 µg/ml concentration in the brain which was significantly higher than the oral CPZ suspension administration (30.46±7.24 µg/ml). The developed formulation was stable for 3 months. CONCLUSION: The study concluded that the developed CPZ-NLC could significantly improve the bioavailability with quick delivery to the brain.

Modeling and optimization of direct dyes removal from aqueous solutions using activated carbon produced from sesame shell waste.

Today, there is a significant concern in the industry regarding the disposal of wastewater containing dyes into the environment, so the management and appropriate disposal of these wastes in the environment are considerable. The main aim of this study is to assess the efficiency of activated carbon (AC) prepared from sesame shells to remove direct dyes from aqueous solutions. According to the results, AC prepared from sesame shell had a high specific surface area (525 m2/g) and porous structure. The results demonstrated that the adsorbent had high potential to remove direct dyes as 84.5% of direct brown 103 (DB103), 93.08% of direct red 80 (DR80), 93.37% of direct blue 21 (DB21) and 98.39% of direct blue 199 (DB199) under the optimal conditions of adsorbent dose 4.8 g/L, contact time 19 min, pH 3 and initial dye concentration 12 mg/L. The experimental results showed that kinetic data were best described by the pseudo-second-order model (R2 = 0.989) while isotherm data were best fitted by the Freundlich model (R2 = 0.994). In the present study, not only was the produced waste used as a useful and economically valuable material, but it was also applied as an effective adsorbent to remove direct dyes from industrial effluents and reduce environmental pollution.

Formulation Development of Directly Compressible Tablets Incorporating Trisamo Extract With Synergistic Antioxidant Activity.

This work investigates the synergistic antioxidant activity of the compositions of Trisamo (TSM) herbal formula containing the dried fruits of Terminalia chebula, Terminalia arjuna, and Terminalia bellirica. An augmented simplex lattice design was utilized to investigate the synergistic antioxidant activity, finding an equal mass ratio among the three herbal drugs to exhibit optimal synergistic antioxidant activity, with a combination index of less than 0.8. The optimal TSM extract was used to prepare directly compressible tablets employing a Box-Behnken design response surface methodology, optimizing compressional force (500, 1000, and 1500 psi), sodium starch glycolate (0%, 2%, and 4%), and magnesium stearate (0.5%, 1.0%, and 1.5%). Optimal parameters were a compressional force of 1000 psi, 2% sodium starch glycolate, and 0.5% magnesium stearate. The TSM extract tablet had a weight of 600.06 mg, a diameter of 12.78 mm, a thickness of 4.12 mm, a hardness of 6.85 kP, a friability of 0.30%, and a disintegration time of 1.81 min. Computer model predictions were verified with a low percentage error (≤ 10.00%). After 6 h, phenolic compounds were dissolved to an extent of approximately 40%-80%, including gallic acid (57.11%), corilagin (38.64%), chebulagic acid (58.49%), and chebulinic acid (81.44%). Stability data revealed that the phenolic compounds were retained for 3 months compared to the initial time point, with gallic acid at 81.43% and 100.27%, corilagin at 94.81% and 87.85%, chebulagic acid at 92.22% and 69.83%, and chebulinic acid at 107.00% and 85.54% at 30°C/75% RH and 45°C/75% RH, respectively. The summation of these four compounds did not change significantly when stored under either set of conditions. In summary, mixture design and response surface design were successfully utilized in the optimization of TSM extract tablets with synergistic antioxidant activity.

Quality by Design (QbD) Approach to Develop Colon-Specific Ketoprofen Hot-Melt Extruded Pellets: Impact of Eudragit® S 100 Coating on the In Vitro Drug Release.

BACKGROUND: A pelletizer paired with hot-melt extrusion technology (HME) was used to develop colon-targeted pellets for ketoprofen (KTP). Thermal stability and side effects in the upper gastrointestinal tract made ketoprofen more suitable for this work. METHODS: The pellets were prepared using the enzyme-triggered polymer Pectin LM in the presence of HPMC HME 4M, followed by pH-dependent Eudragit® S 100 coating to accommodate the maximum drug release in the colon by minimizing drug release in the upper gastrointestinal tract (GIT). Box-Behnken Design (BBD) was used for response surface optimization of the proportion of different independent variables like Pectin LM (A), HPMC HME 4M (B), and Eudragit® S 100 (C) required to lower the early drug release in upper GIT and to extend the drug release in the colon. RESULTS: Solid-state characterization studies revealed that ketoprofen was present in a solid solution state in the hot-melt extruded polymer matrix. The desired responses of the prepared optimized KTP pellets obtained by considering the designed space showed 1.20% drug release in 2 h, 3.73% in the first 5 h of the lag period with the help of Eudragit® S 100 coating, and 93.96% in extended release up to 24 h in the colonic region. CONCLUSIONS: Hence, developing Eudragit-coated hot-melt extruded pellets could be a significant method for achieving the colon-specific release of ketoprofen.

Unlocking the Luminescent Potential of Fish-Scale-Derived Carbon Nanoparticles for Multicolor Conversion.

This study introduces a novel approach to addressing environmental issues by developing fish-scale carbon nanoparticles (FSCNPs) with a wide range of colors from discarded fish scales. The process involves hydrothermally synthesizing raw tamban (Sardinella) fish scales sourced from Universal Canning, Inc. in Zamboanga City, Philippines. The optimization of the synthesis was achieved using the response surface methodology with a Box-Behnken design. The resulting FSCNPs exhibited unique structural and chemical properties akin to carbonized polymer dots, enhancing their versatility. The solid-state fluorescence of these nanoparticles can be modulated by varying their concentration in a polyvinylpyrrolidone matrix, yielding colors such as blue, green, yellow, and red-orange with Commission Internationale de l'Eclairage coordinates of (0.23, 0.38), (0.32, 0.43), (0.37, 0.43), and (0.46, 0.48), respectively. An analysis of the luminescence mechanism highlights cross-linking emissions, aggregation-induced emissions, and non-covalent interactions, which contribute to concentration-dependent fluorescence and tunable emission colors. These optical characteristics suggest that FSCNPs have significant potential for diverse applications, particularly in opto-electronic devices.

Optimized biosynthesis of lytic enzymes by special Trichoderma citrinoviride.

The use of Trichoderma filamentous fungi in the wide concept of biocontrol is still a highly relevant topic. The multifaceted nature of their impact on phytopathogenic microorganisms results from the species diversity and complexity of their antagonistic action. The presented research aimed to determine optimal cultivation conditions of two T. citrinoviride strains for the biosynthesis of major enzymes especially those involved in the biocontrol process. Culture conditions were optimized using a three-factor Box-Behnken design to maximize the yield of chitinase and lichenase. The following independent variables were included in the model: incubation temperature, initial pH, and supplementation with fungal biomass. As a result of statistical optimization, unprecedented activities of extracellular lytic enzyme were achieved. For the B1 and B3 strains, the optimal pH was 3.5 or 7.5, respectively, in the determination of chitinase biosynthesis. It was similar for the biosynthesis of ß-1.3 and ß-1.4 glucanases, but at higher cultivation temperature. The exception was the B3 strain, for which the optimal pH in glucanase biosynthesis was 5.5. The most stimulating culture temperature in the process of chitinase biosynthesis and ß-1.3 and ß-1.4 glucanases was above 25 °C. In that, the levels of enzyme biosynthesis and corresponding composition culture environment were confirmed to be strain-dependent.

Optimization of ultrasonically extracted ß-sitosterol from Berberis jaeschkeana using response surface methodology.

Berberis genus is recognized as a significant source of ß-sitosterol and polyphenols. The inclusion of ß-sitosterol into various health-related formulations has widened its potential in the pharmaceutical and nutraceutical industries. Process optimization ensures the maximum efficiency, consistency, and yield. In the current study, we employed mutual interaction effect to extract the ß-sitosterol from the root bark of Berberis jaeschkeana using ultrasonic-assisted extraction (UAE) technique. In order to identify the optimal extraction parameters, we conducted a series of 29 experiments, varying factors, such as amplitude level, solid-to-liquid ratio, extraction time, and temperature. The mutual interaction effect encompasses several key components, including the Box-Behnken design, assessment of model fitness, coefficient of determination, analysis of variance (ANOVA), and the creation of three-dimensional (3D) response curves of response surface methodology (RSM). The outcomes of the analysis revealed notable model fitness, highlighting the presence of linear, quadratic, and interactive effects among the various factors examined. The optimized UAE conditions (amplitude level of 30%, time of 10 min, solid-to-liquid ratio of 20, and temperature at 50°C) were applied. Under the most favorable extraction conditions, the ß-sitosterol was identified and quantified from Berberis jaeschkeana using high-performance liquid chromatography (HPLC). The ß-sitosterol yield was measured at 43.52 mg per gram of the sample. Conclusively, the optimization approach for UAE using the mutual interaction effect contributes to a more rapid extraction process, resulting in a higher yield of ß-sitosterol. Furthermore, this study design could be extended to other valuable species or compounds to efficiently extract nutraceutical compounds and enhance the sustainable utilization of natural products.

Reappraisal of different agro-industrial waste for the optimization of cellulase production from Aspergillus niger ITV02 in a liquid medium using a Box-Benkhen design.

High-value metabolites, such as enzymes and biofuels, can be produced from various agro-industrial waste containing high percentages of cellulose and hemicellulose. Aspergillus niger ITV02 demonstrates high potential in cellulases production, the key enzyme for converting lignocellulosic materials into fermentable sugars to produce second-generation bioethanol (bioethanol 2G). This study evaluated five lignocellulosic residues of agricultural importance: sugarcane bagasse (SCB), sorghum bagasse (SB), corn stubble (CS), barley straw (BS) and rice husk (RH) as substrates for cellulase production. The temperature, pH and stirring conditions were optimized using a Box-Behnken design to identify the most suitable conditions for cellulase production while minimizing nitrogen concentrations. The results indicate that the best way of propagation A. niger ITV02 is through the use of spores as an inoculant, in conjunction with the use of materials with a high cellulose/lignin ratio, such as CS and SB for the generation of cellulases. These conditions promote the expression of cellulases towards ß-glucosidase production, unlike materials with lower cellulose/lignin ratios like BS and RH, which exhibited lower cellulase activity. The optimal conditions for cellulase production by A. niger ITV02 were determined to be 33 °C, pH 5.3, and 200 rpm, resulting in a 1.7-fold increase in Exoglucanase (FPase activity) (from 0.127 to 0.215 U/mL). These findings demonstrate the potential to enhance FPase activity by utilizing substrates with high cellulose/lignin content and implementing optimal operational conditions without the need to raise the nitrogen content of the basal medium, thus mitigating the economic impact of cellulase production.

Development and optimization of hydrogel-forming microneedles fabricated with 3d-printed molds for enhanced dermal diclofenac sodium delivery: a comprehensive in vitro, ex vivo, and in vivo study.

With the developing manufacturing technologies, the use of 3D printers in microneedle production is becoming widespread. Hydrogel-forming microneedles (HFMs), a variant of microneedles, demonstrate distinctive features such as a high loading capacity and controlled drug release. In this study, the conical microneedle master molds with approximately 500 µm needle height and 250 µm base diameter were created using a Stereolithography (SLA) 3D printer and were utilized to fabricate composite HFMs containing diclofenac sodium. Using Box-Behnken Design, the effects of different polymers on swelling index and mechanical strength of the developed HFMs were evaluated. The optimum HFMs were selected according to experimental design results with the aim of the highest mechanical strength with varying swelling indexes, which was needed to use 20% Gantrez S97 and 0.1% (F22), 0.42% (F23), and 1% (F24) hyaluronic acid. The skin penetration and drug release properties of the optimum formulations were assessed. Ex vivo studies were conducted on formulations to determine drug penetration and accumulation. F24, which has the highest mechanical strength and optimized swelling index, achieved the highest drug accumulation in the skin tissue (17.70 ± 3.66%). All optimum HFMs were found to be non-cytotoxic by the MTT cell viability test (> 70% cell viability). In in vivo studies, the efficacy of the F24 was assessed for the treatment of xylene-induced ear edema by contrasting it to the conventional dosage form. It was revealed that HFMs might be an improved replacement for conventional dosage forms in terms of dermal diseases such as actinic keratosis.

Acoustic resonance technology and quality by design approach facilitate the development of the robust tetrandrine nano-delivery system.

The aim of this study was to develop a sufficiently robust tetrandrine (Tet) nano-delivery system using acoustic resonance (AR) technology and freeze-drying technology. This system can effectively improve the solubility and dissolution properties of Tet, along with high stability and scale-up adaptability. Firstly, 54 stabilizers were screened simultaneously in a high-throughput manner with the help of AR technology to fully explore the optimal prescription space of tetrandrine nanosuspension (Tet-NS). The Plackett-Burman design was used to screen for critical variables severely affecting the quality of Tet-NS. The Box-Behnken design was used to investigate and optimize critical variables to obtain optimal nanosuspensions. The optimal prescription was successfully scaled up by 100 times, which was the initial exploration of its commercial scale production. Solidification studies have shown that formulations with 2.44% fructose as the cryoprotectant have excellent redispersibility. Compared with pure Tet, Tet in Tet-NS showed a significant increase in solubility and dissolution rate in water. Fourier transform infrared (FT-IR) demonstrated that no significant interactions occurred between the drug and excipients in Tet-NS. Powder x-ray diffraction analysis (PXRD) indicated that some of the Tet transformed into amorphous state during the preparation process. In short-term stability study, Tet-NS successfully maintained its physical stability. In summary, under the guidance of the QbD concept, this study rapidly developed Tet-NS using acoustic resonance technology, which can effectively improve the solubility and dissolution properties of Tet. During the development of Tet-NS, AR technology has demonstrated high particle size reduction capability, the ability to process multiple sets of formulations in parallel, and excellent scale-up capability. Meanwhile, the method and concept of this study are not limited to Tet, but also applicable to other poorly water-soluble drugs.

Enhanced D-pantothenic acid biosynthesis by plasmid-free E. coli through sodium pyruvate addition combined with glucose and temperature control strategy.

AIMS: D-Pantothenic acid (D-PA) is an important vitamin widely used in the feed, pharmaceutical, and food industries. This study aims to enhance the D-PA production of a recombinant Escherichia coli without plasmid and inducer induction. METHODS AND RESULTS: The fermentation medium in shake flask was optimized, resulting in an 39.50% increased D-PA titer (3.32 g L-1). Subsequently, the fed-batch fermentation in a 5-L fermenter were specifically investigated. Firstly, a two-stage temperature control strategy led to a D-PA titer of 52.09 g L-1. Additionally, a two-stage glucose feeding was proposed and D-PA titer was increased to 65.29 g L-1. It was also found that appropriate amount of sodium pyruvate was beneficial to cell growth and D-PA synthesis. Finally, a two-stage glucose feeding combined with sodium pyruvate addition resulted in a substantially improved D-PA production with a titer of 72.90 g L-1. CONCLUSION: The D-PA synthesis was significantly improved through the fermentation process established in this work, that is sodium pyruvate addition combined with the temperature and glucose control strategy. The results of this study could provide significant reference for the industrial fermentation production of D-PA.

Application of Polydopamine-Based Magnetic Solid-Phase Extraction for Highly Sensitive Determination of Aristolochic Acid I from Traditional Chinese Medicine Samples.

A low cost-effective and simple synthesis method combining magnetic solid-phase extraction (MSPE) and high-pressure liquid chromatography was developed for the analysis of aristolochic acids I (AAI) in traditional Chinese medicine samples. A novel polydopamine (PDA) modified magnetic nanoparticles with one single carbon layer (Fe3O4@1C NPs) via one-pot hydrothermal approach was prepared and then successfully employed to extract AAI for the first time. Dopamine (DA) can form a PDA layer on Fe3O4@1C NPs surface through self-polymerization to form Fe3O4@1C@PDA. As a surface modifier of DA, PDA offered more adsorption sites to AAI due to π-π stacking, hydrogen bonding and electrostatic interactions. The parameters of MSPE were optimized by univariate and multivariate methods (Box-Behnken design) in detail. High degree of linearity was obtained in the range of 0.05-200.0 µg/mL. The limits of detection (S/N = 3) and quantification (S/N = 10) were 0.08 and 0.25 µg/mL, respectively. The recoveries of AAI in spiked Xiaoqinglong mixture samples were in the range of 86.7 to 108.5% with the relative standard deviation of less than 5.2%. Thus, a fast, convenient, sensitive and eco-friendly method was successfully proposed and became a promising approach for the determination of AAI in herbal plants or its preparation in the manufacturing procedure.

Formulation Optimization and Evaluation of Patented Solid Lipid Nanoparticles of Ambrisentan for Pulmonary Arterial Hypertension.

BACKGROUND: Ambrisentan is a new endothelin receptor antagonist extensively used to manage pulmonary or pulmonary arterial hypertension. OBJECTIVE: The therapeutic efficacy of Ambrisentan is limited due to its reduced solubility, higher log P (3.4), and thus less bioavailability. The recent investigation was concentrated on the improvement of solubility, and bioavailability of Ambrisentan for the therapy of hypertension via solid lipid nanoparticles (SLN) administered orally. METHODS: XRD evaluated the compatibility of Ambrisentan with lipids with FTIR, DSC, and crystalline nature. The SLN was developed by High-pressure homogenization method. The Glyceryl monostearate and Tween 80 indicated the highest solubility, hence selected. The optimization was performed with Box-Behnken Design considering the concentration of GMS (X1), Tween 80 (X2), stirring speed (X3) as independent factors and particle size (Y1), entrapment efficiency (Y2) as dependent factors. The Patents on the SLN are Indian 202321053691, U.S. Patent, 10,973,798B2, U.S. Patent 10,251,960B2, U.S. Patent 2021/0069121A1 and U.S. Patent 2022/0151945A1. RESULTS: The optimized batch F1 showed particle size (130 nm), ZP (-18.9 mV), and entrapment efficiency (85.73 %). The dual release pattern (prompt and sustained) was achieved with the SLNloaded Ambrisentan for about 24 hours. The lyophilized sample was subjected to SEM, which also revealed a spherical shape of a colloidal dispersion with a particle size of 126 nm. Hence, the F1 batch is highly recommended for solid oral delivery and also for the pilot-plant scale-up. CONCLUSION: A marked improvement in the solubility and dissolution of Ambrisentan was attained with the SLN. Moreover, the sustained delivery via the oral route enabled the patient's comfort, compliance, and therapeutic efficacy.

Integrated adsorption and electrochemical sensing of Th(IV) ions using graphene oxide and chitosan decorated magnetite-based adsorbent.

Nuclear waste management is a crucial aspect as the most significant threat to the ecosystem is caused by radioactive waste in which thorium contamination remains a prominent issue. This work represents an integrated approach for the elimination of thorium through the adsorption technique and subsequent electrochemical sensing using Magnetite@Graphene Oxide@Chitosan (M@GO@Cs). Moreover, the sorption of Th(IV) ions is optimized through batch studies, which are consistent with the results derived from ANOVA using the Box-Behnken Design model, and the ideal parameters resulted in 95.79% removal efficiency of Th(IV) ions using 6 mg of adsorbent in 10 mL of 50 mg/L Th(IV) ions solution at a pH of 5 within 20 min. Maximum adsorption capacity (833.33 mg/g) is obtained from Langmuir adsorption isotherm and process was aligned with the pseudo-second-order kinetic model. M@GO@Cs exhibited high recyclability sustaining high performance across nine consecutive adsorption-desorption cycles while maintaining excellent removal efficiency up to 85%. Furthermore, the electrochemical characterization of the synthesized M@GO@Cs nanoadsorbent was studied using the Cyclic Voltammetry, and Electron Impedance Spectroscopy techniques and quantification of Th(IV) ions was done utilizing the Differential Pulse Voltammetry method with the Limit of Detection (LOD) of 0.2 mg/L within a linear range of 10-100 mg/L.

Optimization of extraction process of polysaccharide from Phylloporia fontanesiae and its simulated digestion in vitro.

In this study, Phylloporia fontanesiae polysaccharide was successfully isolated through a sequential water extraction and alcohol precipitation process. Utilizing the Box-Behnken design, the extraction process was optimized based on single-factor experiments, considering variables such as the material-to-liquid ratio, extraction temperature, extraction time, and the number of extractions. The polysaccharide composition of P. fontanesiae is predominantly composed of mannose, glucuronic acid, glucose, and galactose, with a molar mass ratio of 4.31:4.10:36.83:1, along with minor amounts of aminoglucose and fucose. The polysaccharide fraction of P. fontanesiae comprises two distinct components, possessing relative molecular masses of 8.85 kDa and 134.03 kDa. Notably, the polysaccharide exhibited significant antioxidant activity. After undergoing simulated gastrointestinal digestion, no significant changes were observed in its antioxidant activity, molecular weight, or monosaccharide composition. This study not only enhanced the extraction efficiency of P. fontanesiae polysaccharide but also provided valuable insights into its composition, structure, and digestion characteristics. PRACTICAL APPLICATION: The optimum extraction process, stability, and antioxidant activity of Phylloporia fontanesiae polysaccharide during simulated digestion of gastrointestinal tract were studied. The results provide a theoretical basis for the development and application of this polysaccharide in the field of food and health products.

Application of Box-Behnken design in the optimization and development of albendazole-loaded zein nanoparticles as a drug repurposing approach for colorectal cancer management.

Colorectal cancer (CRC) is the second cancer worldwide representing a major global health challenge. Numerous effective anticancer drugs have been developed in the last decade, yet the problem remains due to their low therapeutic index and nonspecificity. A new anticancer therapeutic paradigm is based on repurposing and nanoformulating drugs. Albendazole (ALB), a popular anthelmintic agent, was recently repurposed against CRC cells. In this study zein, an amphiphilic protein, was used to formulate nanoparticles (NPs) loaded with ALB. Box-Behnken design was selected to optimize the loaded NPs, the concentrations of polyvinyl alcohol, acetic acid, and the weight of zein were the independent variables. The dependent variables were the particle size, polydispersity index, and zeta potential. The optimized formula displayed a size of 84.3 ± 0.41 nm, PDI 0.13 ± 0.012, and a zeta potential of 42.5 ± 2.35 mV. ALB was successfully encapsulated into zein NPs and the release study revealed a desirable pH-responsive drug release behavior, that was negligible release during the first 2 h at pH 1.2 and progressive in the simulated colon environment reaching 71.1 ± 0.34 % at 6 h and 92.4 ± 1.11 % at 24 h. The anticancer effect of the loaded NPs on the human HCT116 cells showed favorable effects at 1 µM concentration with a significant decrease in the IC50 at days 2 and 3 upon loading albendazole into zein NPs. Zein nanoparticles proved to be prospective nanocarriers that could be used for the delivery of repurposed drugs in CRC treatment.

Optimizing dielectric constant of noncommercial biobased fibres - Acacia Nilotica, Acacia Leucophloea and Prosopis juliflora - For composite applications with selected fillers.

In recent decades, most electrical/electronic products possess non - biodegradable components. The expanding consumption of these goods and their eventual disposal pose a serious environmental threat. To cope up with this issue, biodegradable electrical/electronic components using biobased fibres can be an alternative option. The novel exploration of this research work is the usage of underutilized biobased fibres, such as Acacia Nilotica, Acacia Leucophloea and Prosopis Juliflora, as sustainable alternatives to traditional synthetic fibres in natural fibre-reinforced epoxy composites. The novelty lies in the combination of these natural fibres with ceramic fillers like Silicon Carbide, Boron Nitride and Aluminium Oxide, aiming to enhance the composite properties. The objective of the study is to optimize the type of fibre, fibre content (2 wt%, 4 wt% and 6 wt%) and types of fillers (1 wt%) combinations using the Box-Behnken Design to improve the dielectric properties of these composites. Analysis of Variance (ANOVA) is used to evaluate the relevance of each parameter on dielectric constant of the biobased fibre reinforced epoxy composite. The significant outcome is identified that Prosopis Juliflora (6 wt%) combined with Boron Nitride (1 wt%) yields an optimal dielectric constant of 1.11, highlighting the potential of these biobased fibres to serve as effective substitutes for conventional glass and carbon fibres for electrical insulating materials used in switchboards and socket pins to prevent electrical conduction and ensure safety. This research not only contributes to the field of sustainable materials but also addresses critical environmental concerns associated with electric/electronic waste.

Quality by design-based approach for the development of an analytical method for quantifying ponatinib in rat plasma.

Ponatinib is a potent tyrosine kinase inhibitor that is approved for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. To further expand its clinical applications, accurate quantification of ponatinib in plasma is essential. In this study, we developed and validated a sensitive and selective high-performance liquid chromatography (HPLC) method coupled with a fluorescence detector (FLD) to measure ponatinib concentrations in rat plasma using the Analytical Quality by Design approach. Briefly, we screened and optimized the critical method parameters using the Taguchi and Box-Behnken designs. The developed method had excellent linearity in the range of 1-1000 ng/mL, sensitivity, and reproducibility, and required minimal sample volume and a short run time. Compared with previously reported HPLC-ultraviolet (UV) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods, this HPLC-FLD method offers superior sensitivity, simpler sample preparation, and greater efficiency. We successfully used this method in a pharmacokinetic study in rats to obtain reliable data on ponatinib plasma concentrations. Altogether, this analytical method will be applicable in several analytical conditions and will support further pharmacokinetic and clinical investigations of ponatinib for various cancer treatments.

Synthesis of a triazine based COF and its application for the establishment of an electrochemical sensor for the simultaneous determination of Cd2+ and Pb2+ in edible specimens using Box-Behnken design.

The study presented here describes the characterization and synthesis of a triazine-based covalent organic framework using different analytical procedures such as scanning electron microscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, cyclic voltammetry, Brunauer-Emmett-Teller analysis, and electrochemical impedance spectroscopy. The synthesized COF was then utilized as an electrocatalytic modifier for the selective and sensitive determination of Pb2+ and Cd2+ at nanomolar levels via square wave anodic stripping voltammetry. A Plackett-Burman design was employed to screen operational parameters influencing the sensitivity of the electroanalytical method, followed by optimization of the significant variables using Box-Behnken design. A linear response over 1.0-110.0 nmol L-1 and 5.0-300.0 nmol L-1 range for Pb2+ and Cd2+, with detection limits of 1.1 and 1.8 nmol L-1, respectively. Furthermore, the selectivity of the presented electrode over different species was evaluated with no significant interference found. The sensor was applied effectively to determine of Pb2+ and Cd2+ ions in samples.