Box-Behnken Design Research Articles

Upcycled cosmetic ingredients: extraction process optimization via green solvents by the means of I-optimal and Box–Behnken designs

Current trends are shifting attention to the sustainable valorization of food bio-waste management and by-product utilization, as they are rich in nutrients and bioactive compounds, such as dietary fiber, polyphenols, and peptides. Upcycled ingredients and green cosmetics are becoming more and more appealing concepts in the nutraceutical and cosmetic industries encouraging them to invest and develop sustainable products aligning with the green concept of circular economy. In this research, we focused on the waste products (peels) of super exotic fruits Litchi chinensis and Selenicereus undatus, which are packed with antioxidants, fibers, vitamins, and minerals. Extraction of the peels with green solvent (propylene glycol) was performed and optimized by the means of an I-optimal and box-behnken designs with different independent variables for each design and total phenolic content (TPC) as a response. The resulted optimized extract of lychee peels propylene glycol extract (LPPG) was evaluated in terms of anti-tyrosinase activity, resulting in an (IC50 = 264.1 ± 16.9 µg/mL) with an average inhibition percentage of (92.33%), DPPH assay was performed, revealing antioxidant activity of (2666.7 ± 68.71 µmol ascorbic acid/mL) and (24,774.68 ± 834.67 µmol ascorbic acid/mL) using ABTS assay. As for dried dragonfruit propylene glycol extract (DDPG), the antioxidant activity was found to be (1299.82 ± 20.80 µmol Ascorbic acid/mL) using DPPH assay and (1510.506 ± 12.93 µmol Ascorbic acid/mL) using ABTS assay. In conclusion, optimization of the extraction process of food by-products using propylene glycol as a solvent may offer a valuable sustainable cosmetic ingredient.

A Novel Platform Featuring Nanomagnetic Ligand Fishing Based on Fixed-Orientation Immobilized Magnetic Beads for Screening Potential Cyclooxygenase-2 Inhibitors from Panax notoginseng Leaves

A novel screening platform based on an Fe3O4@C@PDA-Ni2+@COX-2 ligand fishing combination with high-performance liquid chromatography–mass spectrometry was first designed, synthesized, and employed to screen and identify COX-2 inhibitors from Panax notoginseng leaves. The obtained magnetic nanoparticles exhibit outstanding preconcentration ability that allows for controlling the enzyme orientation to avoid enzyme active site blocking, conformational changes, or denaturing during immobilization. The as-prepared Fe3O4@C@PDA-Ni2+@COX-2 composite was carefully characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectrometry (FT-IR), Xray powder diffraction (XRD), thermal gravimetric analyzer (TGA), vibrating sample magnetometer (VSM), and Zeta potential analysis. The analytical parameters influencing the magnetic solid-phase fishing efficiency were optimized by univariate and multivariate methods (Box–Behnken design) by testing a positive control and celecoxib with active and inactive COX-2. Under the optimized ligand fishing conditions, twelve potential COX-2 inhibitors were screened and characterized in Panax notoginseng leaves. The results indicate that the proposed method provides a simple, feasible, selective, and effective platform for the efficient screening and identification of active compounds from Chinese herbal medicine. It has guiding significance for the synthesis and development of novel anti-inflammatory drugs, and provides a reference for the efficient discovery of anti-inflammatory drugs or lead compounds from the complex system of Chinese herbal medicine.

Optimization of orange-fleshed sweet potato (SG 18-88-01) flour preparation for maximum carotenoid retention using response surface methodology

Due to the nature of the flour processing methods, the nutritional content of sweet potatoes decreases. Knowing the optimal flour processing conditions is important to maximize the nutrition that one can obtain from sweet potato flour. In this study, optimized flour preparation conditions for maximum β-carotene retention of orangefleshed sweet potato (SG 18-88-01) (OFSP) were determined using response surface methodology. A two-level randomized Box-Behnken design was utilized to assess the effects of blanching temperature (60 to 100°C), blanching time (1 to 3 mins), and drying temperature (50 to 70°C). The optimal conditions were blanching for one minute at 97.75° C and drying at 66.30°C. Using the said conditions, the experimental vitamin A content was reported to be 373.95 IU/g, antioxidant activity was 0.55 mg TE/g, and color values were 82.81 L*, 6.40 a*, 24.92 b*, and 1.32 radians hue angle. The predicted and experimental values were compared using paired t-test and showed no significant differences at p>0.05 and p>0.01. Hence, the model was adequate and had good predicting capacity. The optimized OFSP flour has 5.50±0.80% moisture, 2.14±0.22% ash, 2.51±0.24% crude protein, 3.07±0.09% crude fiber, 0.47±0.03% crude fat, and 86.31% nitrogen-free extract content. The flour has a water absorption index (WAI) of 5.90±0.15 g/g, water solubility index (WSI) of 55.26±0.03%, and swelling power of 13.23±1.34 g/g. Given the results, the generated OFSP flour is ideal to use for food production, particularly in bakery products. It was also revealed that consuming 4-10 g of the flour can meet the Recommended Nutrient Intake in all Filipino age groups.

Optimized Photocatalytic Degradation of Methylene Blue Using Titaniferous Sand/ZnO Composite: A Sustainable Approach to Wastewater Treatment

This study explores a novel approach to enhancing photocatalytic efficiency by utilizing an industrial residue, titaniferous sand, in combination with ZnO. The purifying efficiency of this semiconductor mixture was studied for the removal of methylene blue in a fixed-bed reactor. The main objective was to find out with what percentage the titaniferous sand could be incorporated into the ZnO for maximum photocatalytic performance. Box-Behnken Design (BBD) in the Response Surface Methodology (RSM) was used to optimize the operative parameters. The influence of titaniferous sand/ZnO ratio (A:1-2.8), pH (B:4-10) and irradiation time (C:120-480 minutes) on the degradation efficiency of the dye was studied. Initial concentrations of methyl blue and total semiconductor mixture were set at 25 mg/L and 10 g/L, respectively. The ANOVA analysis showed that the photocatalytic process was significantly affected by a positive individual effect of the titaniferous sand/ZnO ratio and the irradiation time. A quadratic polynomial of the second order accurately represented the experimental values with a correlation coefficient R2 of 0.9921. In addition, this model had a p-value of less than 0.0001 and an F-value of 84.09. Thus, the model used was quite appropriate. Optimal conditions were obtained for a ratio (titaniferous sand/ZnO) of 1.51057, i.e. a titaniferous sand percentage of 66%, a pH of 9.97487 and an irradiation time of 479.765 minutes. Under these conditions, a degradation of 99.4915% was obtained. In addition, the photocatalytic degradation kinetics of methylene blue on the titaniferous sand and ZnO mixture followed the Langmuir-Hinshelwood model and was of the first order with an apparent kinetic constant of 0.402 h-1.

OPTIMIZATION OF Al-BASED AMORPHOUS COATINGS BY WARM SPRAYING BASED ON A NUMERICAL SIMULATION AND A RESPONSE-SURFACE METHODOLOGY

Al-based fully amorphous coatings with low porosity were prepared using a warm-spraying technology by combining numerical simulations and a response-surface methodology (RSM). The influences of spraying parameters (reactant flow rate, oxygen/fuel (O/F) ratio, coolant flow rate, and spraying distance) on the particle temperature and velocity were investigated using numerical simulation methods. On this basis, the response-surface equations for temperature and the velocity of the particles were established using the Box-Behnken Design (BBD) methods. The RSM was used to analyze the influence of the interactions between the spraying parameters on the temperature and the velocity of the particles. The optimum spraying parameters (OSP) predicted by the response optimizer were 0.012047 kg/s for the reactant flow rate, 0.011034 kg/s for the coolant flow rate, 2.7 for the O/F ratio, and 142 mm for the spraying distance. According to the OSP, the Al-based fully amorphous coatings with a porosity of 0.08% were obtained by warm-spraying experiments. This work provides guidance for the production of Al-based fully amorphous coatings with low porosity using warm spraying.

Enzymatic Interesterification of Cold-Pressed Maqui (Aristotelia chilensis (Mol.) Stuntz) Seed Oil and Belly Oil from Rainbow Trout (Oncorhynchus mykiss) Through Supercritical CO2

A new antioxidant lipid (AL) was synthesized from rainbow trout (Oncorhynchus mykiss) belly oil and cold-pressed maqui (CPM) (Aristotelia chilensis (Mol.) Stuntz) seed oil via enzymatic interesterification using Thermomyces lanuginosus in supercritical CO2 medium. A Box–Behnken design with 15 experiments was employed, with the independent variables being the following: belly oil/CPM oil ratio (10/90, 50/50, and 90/10, w/w), supercritical CO2 temperature (40.0, 50.0, and 60.0 °C), and supercritical CO2 pressure (100.0, 200.0, and 300.0 bar) for enzymatic interesterification. A multiple optimization was conducted based on the response variables yield and eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and tocopherol contents. The optimized conditions for the AL synthesis were: 81.4/18.6 (w/w), 40.0 °C and 299.99 bar, respectively. The corresponding responses variables were: 77.10% for yield, 5.12 and 4.95 g·100 g−1 total fatty acids for EPA and DHA, respectively, and 217.96, 4.28, 3.48, 64.48, and 6.39 mg·kg−1 oil for α-tocopherol, α-tocotrienol, β-tocopherol, γ-tocopherol, and δ-tocopherol, respectively. A novel AL was successfully synthesized starting from two abundant natural resources commonly considered as by-products during industrial processing. In agreement with the high EPA, DHA, and tocopherol presence, this AL can be recommended to be employed in nutritional and therapeutic supplements, according to its health benefits, particularly concerning antioxidant and anti-inflammatory properties.

Natural acidic deep eutectic solvent-mediated microwave-assisted simultaneous hydrodistillation, hydrolysis, and extraction for obtaining essential oils, gallic acid and ellagic acid from Liquidambar formosana leaves and fruits

In this study, an improved method of naturally acidic deep eutectic solvent-mediated microwave-assisted simultaneous hydrodistillation, hydrolysis, and extraction (MSHDHE) was employed to obtain essential oils, gallic acid and ellagic acid from Liquidambar formosana leaves and fruits. The obtained target analytes were then analyzed via GC‒MS and HPLC. The optimal extraction conditions were identified via a Box–Behnken design. Compared with fruits, L. formosana leaves contain more gallic acid and ellagic acid, which have more essential oils. GC‒MS analysis revealed few variations in the composition and content of L. formosana leaves and fruit essential oils. A total of 36 components in the essential oil of L. formosana leaves and 55 components in the essential oil of the fruits were detected via GC‒MS. Compared with classical hydrodistillation and microwave-assisted hydrodistillation, natural acidic deep eutectic solvents outperform conventional extraction solvents (pure water), providing a scientific foundation for the extraction of natural acid deep eutectic solvents consisting of choline chloride and natural organic acids.

Mining, Identification, and Fermentation Optimization of Chitin Deacetylase from a Novel Strain Enterobacter sp. ZCDA27.

Chitin, a natural organic compound with content slightly lower than cellulose, is also known for chitosan, a substance derived from chitin through deacetylation. In this experiment, preliminary screening was conducted using the plate discoloration circle method, leading to the selection of a high-yield CDA-producing strain from 28 candidates through rescreening. Morphological characteristics and 16S rDNA sequence analysis revealed 99.93% homology with Enterobacter sichuanensis strain N24, thus naming this strain Enterobacter strain ZCDA27. Initial fermentation of the strain yielded CDA activity of 9.29 U/mL. Single-factor optimization was then performed, followed by a PB test to screen for significant factors affecting enzyme production. The response surface method was used to further optimize the fermentation conditions. The optimal fermentation conditions for the carbon source, nitrogen source, metal ion, fermentation temperature, time, liquid volume, and initial pH were explored. Significant factors affecting enzyme production, including MgSO4, initial medium pH, and fructose levels, were identified using the PB test. Finally, the fermentation conditions of ZCDA27 were optimized using the Box-Behnken design combined with RSM, which comprised fructose at 1.020%, magnesium sulfate at 0.016%, and peptone at 1%. The fermentation conditions included a temperature of 37, initial pH of 7.1, rotation speed of 140 × g, fermentation time of 28h, inoculation amount of 2%, and liquid volume of 40%. Under these conditions, the enzyme activity of ZCDA27 reached 14.52 U/mL, a 1.6-fold increase from the pre-optimization levels. In summary, this study provides an experimental foundation for further development and application of Enterobacter spp. ZCDA27 CDA.

Optimized Extraction of Sargahydroquinoic Acid, Major Bioactive Substance, from Sargassum yezoense Using Response Surface Methodology

Sargahydroquinoic acid (SHQA), a bioactive compound found in certain Sargassum species, exhibits significant health benefits. This study optimized the extraction of SHQA from Sargassum yezoense using response surface methodology (RSM) and evaluated its antioxidant effects through in vitro and in vivo assays. A Box–Behnken design (BBD) was effectively employed to investigate the effects of incubation temperature, time, and ethanol concentration on SHQA yield, achieving a high coefficient of determination (R2 = 0.961). Analysis of variance (ANOVA) validated the model’s reliability (F = 13.86, p = 0.005) and highlighted ethanol concentration as a highly significant factor (p < 0.001). Optimal extraction conditions were identified as 52.8 °C, 8.3 h, and 74.1% ethanol. The SHQA-maximized extract (SME) contained 67.8 ± 0.6 mg SHQA/g and 25.00 ± 1.01 mg phloroglucinol equivalent/g. SME exhibited antioxidant capacity of 26.45 ± 0.66 mg and 28.74 ± 2.30 mg vitamin C equivalent/g in ABTS and DPPH assays, respectively, and 0.29 ± 0.02 mM FeSO4 equivalent/g in the FRAP assay. Additionally, SME at 50 µg/mL and SHQA at 1 µg/mL inhibited reactive oxygen species (ROS) generation in an H2O2-induced zebrafish model. This study presents the first optimization of SHQA extraction using RSM and demonstrates SHQA’s ROS inhibition in a zebrafish model.

Exploration of synergistically engineered invasomes of fluconazole incorporated with safranal against onychomycosis for enhanced transungual delivery

Objective The preparation of safranal-containing invasomes for fluconazole (FLU-IN) is investigated in the current research work to augment FLU permeation, bioavailability, and solubility via nail for transungual delivery. Methods FLU-IN was prepared utilizing the “thin-film hydration process”, and for optimization, “Box-Behnken design (BBD)” was employed. Entrapment efficiency (EE), Poly-dispersity index (PDI), in vitro FLU release, vesicle size and zeta potential were used to characterize FLU-INopt. Confocal microscopy (CLSM), nail permeation investigation, and Transmission electron microscopy (TEM) were also carried out for further examination. Results The FLU-INopt demonstrated tiny, spherical, sealed-shape vesicles with a vesicle size of 140.3 nm, PDI of 0.1604, in vitro release of 84.32%, and entrapment efficiency of 74.65%. According to the CLSM investigation, the prepared formulation exhibits better FLU penetration over the nail than FLU suspension gel. Compared to the standard fluconazole marketed gel, the anti-fungal investigation showed that the FLU-IN gel has good anti-fungal potential against Trichophyton rubrum, Nakaseomyces glabrata and Candida albicans. Additional research on Wistar albino rats' skin irritancy supports the new FLU-IN formulation's safety for topical treatment. Conclusion The present study supported the claim that the developed invasomal formulation is a desirable vesicular carrier for FLU transungual delivery for the management of onychomycosis.

Synthesis of sodium alginate grafted and silver nanoparticles filled anionic copolymer polyelectrolytes for adsorption and photocatalytic degradation of a cationic dye from water

Sodium alginate (SA) was grafted to poly (acrylonitrile-co‑sodium acrylate-co-acrylic acid). The grafted copolymer was crosslinked with N. N, methylene bis acrylamide (MBA). Silver nanoparticles (AgNPs) were generated in situ within the growing polymer network by reducing 0.1 mM silver nitrate with 0.05 mM ascorbic acid (ASA). The effect of initiator concentration, total monomer concentration, SA weight%, MBA weight% and acrylonitrile (AN):sodium acrylate (NaAA)/ acrylic acid (AA) molar ratios on the grafting were studied. The nanocomposite was characterized and used for adsorption of methylene blue (MB) dye from water. The composite was also used for photocatalytic degradation of the dye in the presence of sun light. The Box-Behnken design (BBD) of response surface methodology (RSM) with different compositions resulted in an optimized composition of 5:1 M ratio of AN:NaAA/AA, 1 wt% MBA and 2 wt% SA. The nanocomposite (SACP5Ag) prepared with the optimized composition showed an equilibrium batch adsorption(qe, mg/g)/removal(R)% of 245/98 from 50 mg/L MB dye in water and a qe /R% of 18.87/31.4 in a fixed bed adsorption at a feed inlet concentration(mgL−1)/inflow rate (mLmin−1)/bed height (mm) of 100/20/25. The composite showed a photocatalytic degradation efficiency of 98 % in sunlight for 80 min and a 1st order rate constant of 0.02 min−1.

UPLC Estimate of Sofosbuvir and Ledipasvir Utilizing Greenness Tool in Conjunction With an Analytical Quality by Design.

Ledipasvir in combination with sofosbuvir approved by regulatory bodies used to treat chronic hepatitis C. The present work investigates the design and development of a new, quick, green, and selective UPLC (ultra-performance liquid chromatography) approach to concurrently quantify sofosbuvir and ledipasvir. Optimization with Box-Behnken design paired the green analytical method and quality by design-based risk assessment. A mobile phase of 65%:35% ethanol by volume and phosphate buffer (15 mM; pH 3.0) was used, with a flow rate of 0.28 mL per minute, to achieve the best chromatographic separation. With linearities ranging from 20 to 100, 4.5-22.5 μg/mL, and R2 values of 0.9999 and 0.9997, respectively, the established UPLC-PDA technique proved sensitive and specific for sofosbuvir and ledipasvir. The stability-indicating test findings demonstrate the degradation under the relevant stress conditions. The most environmentally friendly results were found when the level of environmental sustainability was evaluated using four advanced metrics: GAPI, AES, AMGS, and AGREE. Based on the findings, we came to the conclusion that the UPLC technique that was developed would be effective for the concurrent analysis of sofosbuvir and ledipasvir in tablet medication.

Adsorption and removal of Pb (II) via layer double hydroxide encapsulated with chitosan; synthesis, characterization adsorption isotherms, kinetics, thermodynamics, & optimization via Box-Behnken design

The study aimed to enhance the stability and efficiency of removing bivalent Pb(II) by encapsulating AlNi-layered double hydroxide (LDH) in chitosan and itaconic acid to create an adsorbent with chemically active sites. The resulting material, AlNi-LDH/CS, underwent thorough property analysis using XRD, FT-IR, XPS, EDX, N2 adsorption/desorption isotherm, and FESEM to find out what textural characteristics it has. Specifically, nitrogen adsorption/desorption isotherms were utilized to assess the textural properties of AlNi-LDH/CS. The Al/Ni-LDH/CS surface displayed a specific surface area of 71.95 m2/g and an average pore size of 2.537 nm, consistent with the platelets' external surface. The effects of dose, pH, temperature, and starting concentration on the adsorption process were also investigated in this study. The adsorption characteristics have been examined by means of equilibrium and adsorption kinetics. The adsorption process adhered to the pseudo-second-order and Langmuir isotherm models. The predominant adsorption process was found to be chemisorption, which had an adsorption energy of 28.42 kJ·mol−1. An endothermic and spontaneous adsorption process is suggested by the increase in metal absorption at increasing temperatures. The Box-Behnken design software was utilized to establish the optimal adsorption parameters as pH 5, a dosage of 0.2 g of AlNi-LDH/CS per 25 mL, and an adsorption capacity of 453.05 mg/g for the Pb(II) arsenate solution. For the composite sponge to be most effective in adsorbing arsenate and be used in water purification procedures, these factors are essential. The adsorption process was successfully improved with few planned tests by applying the Box-Behnken design and response surface technique aspects of the Design-Expert software. An evaluation of the adsorbent's reusability using six successive cycles of adsorption and desorption confirmed its stability and showed no discernible decrease in removal efficiency. Additionally, it retained its original chemical composition before and after reuse, showcased consistent efficiency, and maintained uniform XRD data.

Synthesis and characterization of novel magnetic metal organic framework for efficient removal of ketoprofen from aqueous solutions: Mechanism of interaction, adsorption and optimization via BOX-Behnken design

This investigation examines the adsorption and elimination of the anti-inflammatory medication ketoprofen (KTP) in relation to a newly developed magnetic thorium metal-organic framework (MTh-MOF). The study found that KTP absorption on MTh-MOF resulted in a reduction in pore volume, pore size, and surface area, as revealed by N2 adsorption/desorption isotherm analysis used to evaluate the characteristics of the MTh-MOF. Scanning electron microscopy (SEM) showed that the pore radius of MTh-MOF decreased from 1.68 nm to 0.82 nm, demonstrating a consistent and uniform structure. Fourier-transform infrared (FT-IR) spectroscopy was employed to identify the functional groups present in MTh-MOF, while X-ray photoelectron spectroscopy (XPS) was used to confirm the compound's structure. The optimal conditions for achieving a high adsorption capacity were found to be at pH 6 and a MTh-MOF dose of 0.02 g. The results indicated that MTh-MOF displayed a high capacity for absorbing KTP, with the adsorption data fitting well with pseudo-second-order kinetic models and the Langmuir isotherm. The adsorption capacity of MTh-MOF for KTP was determined to be 518 mg/g. The adsorption energy of 28.26 kJ·mol–1 suggested that chemisorption was the predominant mode of adsorption. The process of KTP adsorption on MTh-MOF was observed to be spontaneous, endothermic, and random, as evidenced by the temperature-dependent increases in the thermodynamic parameters (ΔGo, ΔHo, and ΔSo). The adsorption process was optimized using Response Surface Methodology and Box-Behnken design (RSM, BBD). Aromatic rings interact via π-π bonding, while chemisorption involves the development of chemical interactions between the adsorbate and adsorbent. Additionally, electrostatic interactions arise from the attraction or repulsion of charges between the adsorbate and adsorbent, and pore-filling occurs when the adsorbate fills the adsorbent's pores. In order to understand the electrical properties, reactivity, and shape of KTP, density functional theory (DFT) was utilized.

Blended mangosteen/pomegranate peels as a precursor for porous carbon material via microwave assisted‑potassium carbonate activation: Box-Benken design optimization for fuchsin basic and methylene violet dyes removal

Solid waste disposal and water pollution are the critical issues. Thus, this work aims to convert common domestic fruit wastes namely mangosteen peel (MP) and pomegranate peel (PP) into a mesoporous activated carbon (MPPP-AC) via microwave-induced strong alkaline salt (K2CO3) activation. The potential application of MPPP-AC was tested for the removal of two structurally different toxic cationic dyes namely fuchsin basic (FB) and methylene violet (MV). The physicochemical properties of MPPP-AC were analyzed utilizing several analyses such as XRD, SEM-EDX FTIR, pHpzc, and BET analysis. The adsorptive performance of MPPP-AC was optimized by using response surface methodology (RSM) with Box-Behnken design (BBD). Three key adsorption variables including the dose of MPPP-AC (A: 0.02–0.1 g/100 mL), solution pH (B: 4–10), and time of contact (C: 10–60 min) were optimized in the BBD. The highest FB removal and MV removal were found to be 80.2 % and 92.8 % respectively at 0.1 g/100 mL of MPPP-AC dosage and solution pH = 10. Thus, the best fit for the adsorption isotherm data for FB and MV dyes was the Freundlich model, whereas the pseudo-second-order model was best explained for the kinetic data. The MPPP-AC has maximum adsorption capacity for FB (85.5 mg/g) and MV (90.1 mg/g). Various forms of interaction were involved in the MV and FB dye binding process onto MPPP-AC such as the filling of pores, π-π stacking, hydrogen bonding, and electrostatic forces. The finding of this research exhibits the possibility of transforming a blending of MP and PP wastes into activated carbon which shows desirable adsorptive performance for eliminating cationic dyes from water.

Bilastine-Loaded Transethosome Based Nanogel for the Treatment of Allergic Reactions: An In vitro Characterization

Objective: The goal of the current study was to formulate and evaluate bilastine-loaded transethosomal nanogel. Bilastine has 60% oral bioavailability, which restricts the rate of absorption and dissolution and classifies it under BCS class II drugs, which can be overcome by incorporating bilastine in transethosomal nanogel formulation in the treatment of urticaria. Methods: Bilastine-loaded transethosomes were prepared using a thin film hydration method with different proportions of Tween 80 and ethanol by using a rotary evaporator and incorporated into a transethosomal gel using Carbopol 934 as a polymer by dispersion method. Results: The bilastine-loaded transethosomal formulation was optimized by using the “Box Behnken design” and evaluated for various parameters. The optimized formulation was found to be stable, as determined by the zeta potential of −27.0 mV and polydispersity index (PDI) of 0.167, and vesicle size was found to be 183nm and exhibiting the maximum entrapment efficiency of up to 80.23%. The drug content of the transethosomal gel was found to be 81.56%. The best results were obtained with a transethosomal gel prepared with 1% Carbopol 934 (TF7G2). The optimized batch showed prolonged in-vitro release of bilastine for 8 hrs. Ex vivo skin permeation studies showed 76.23 ± 2.63% permeation in comparison with plain gel. Conclusion: Transethosomal nanogel batches were optimized based on drug content, viscosity, uniformity of drug content, zeta potential, spreadability, pH, drug release, and stability testing, exhibiting good results. The results of this investigation showed that the transethosomal nanogel loaded with bilastine might be used to improve bilastine delivery through the skin with greater bioavailability.

Sesamol Loaded Silver Nanoparticles Gel Engineered for Wound Healing via Topical Delivery: Optimization In vitro and Ex vivo Evaluation.

The current investigation involved the development and application of a topical treatment for wound healing for sesamol loaded into the silver nanoparticles (SML-AgNPs). SML-AgNPs were produced through the application of microwave technique. The SML-AgNPs were further optimized utilizing a Box-Behnken design (BBD). The Opt-SML-AgNPs formulation that was optimized demonstrated a particle size of 160.49 ± 1.11 nm, a polydispersity index (PDI) of 0.241 ± 0.54, a zeta potential of -21.09 ± 0.88 mV, and an efficiency of 84.19 ± 1.19%. The morphology of the Opt-SML-AgNPs reveals a spherical structure. The Opt-SML-AgNPs exhibit a higher in vitro drug release rate as compared to the SML suspension. The Opt-SML-AgNPs were incorporated into the carbopol gel (Opt-SML-AgNPG) and evaluated for various parameters. The skin permeation investigation revealed a twofold increase for the Opt-SML-AgNPG formulation when compared to the SML-conventional gel formulation. This finding indicates a prolonged release pattern and an enhanced permeability profile. The Opt-SML-AgNPs formulation exhibited a higher level of antioxidant activity when compared to the SML solution which is beneficial for wound healing. In conclusion, the Opt-SML-AgNPG exhibits considerable potential in effectively penetrating the deeper dermal layers. Therefore, it may be considered that they possess the potential to serve as a suitable nanocarrier to administer topical delivery in the context of treating skin-related illnesses.

Lipid extract from Black Soldier Fly larvae: A high value excipient for solid lipid nanoparticles tailored to tackle atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a complex pathogenesis involving epidermal barrier dysfunction and aberrant lipid composition, particularly ceramides and fatty acids (FA). Conventional management options, such as topical glucocorticoids (GC), often lead to adverse effects upon prolonged usage, prompting the exploration of alternative therapeutic strategies. The lipid extract from Black Soldier Fly larvae (BSFL) biomass, holding a rich blend of FA, holds substantial potential as a novel ingredient to tackle skin barrier impairment. This study aimed to achieve proof-of-concept validation of innovative nanotechnology-based formulations tailored to enhance the topical management of AD. Specifically, solid lipid nanoparticles (SLNs) with BSFL lipid extract were developed to perform both as a carrier for dexamethasone (DEX), a representative GC, and as skin barrier repair adjuvants. Through systematic optimization using Box-Behnken Design, BSFL lipid extract-based SLNs demonstrated favorable physicochemical properties for topical application and satisfactory stability over 2 months. Notably, these SLNs exhibited favorable drug release kinetics, delivering the total DEX payload within a therapeutically relevant timeframe. Furthermore, these nanocarriers showed the ability to permeate human keratinocytes without pronounced toxicity, suggesting their potential utility in enhancing drug delivery and cellular uptake. Overall, these findings suggest that BSFL lipid extract is a promising natural and sustainable ingredient for the development of nanotechnology-driven approaches to AD management, offering a potential avenue for addressing the unmet needs in this challenging dermatologic condition.

Microwave-aided sensitive and eco-friendly HPTLC method for estimation of mirabegron using NBD-Cl as bio-sensing fluorescent probe by Integration of principal component Analysis, response surface modelling and white analytical chemistry approach

A large number of analytical methods have been used in in-vivo pharmacokinetic investigations and assays of mirabegron, which is used to treat overactive bladder. Because mirabegron does not give fluorescence, there is no known chromatographic method that uses this property in conjunction with environmentally safe solvents. In order to develop and assess analytical procedures that are precise, sensitive, environmentally friendly, economical, and easy to use, white analytical chemistry was recently presented. Hence, a microwave-aided HPTLC method with fluorescence detection was developed and applied for mirabegron quantification; this method is both sensitive and environmentally acceptable, and it makes use of NBD-Cl, a bio-sensing fluorescent-probe. The analytical-QbD approach, which includes chemometric and response-surface modeling concepts, was used to design this targeted chromatographic method. Critical method variables and performance parameters were identified and optimized using principal component analysis and Box-Behnken design. The targeted method was used to estimate mirabegron through the development of method operable design range navigation and control strategy. A mobile phase consisting of ethyl-acetate and ethanol (8.0 + 2.0, v/v) was used to develop the chromatogram of NBD-Cl derivatised-mirabegron into 8.0 mm bands on a TLC-plate that was supported with aluminum and precoated with silica-gel G60 F254. In a mirabegron concentration range of 50–250 ng/band, the suggested method exhibited linearity. Results showed that the suggested method has a recovery rate of 98 % to 102 %. When estimating mirabegron, the %RSD for the precision and robustness study was determined to be less than 2.0. The mirabegron %assay in the commercially available formulations was determined to be between 98 % and 102 % of the labelled claimed value. Mirabegron had a limit of detection of 10 pg/band and a limit of quantification of 50 pg/band. Marketed tablet formulations of mirabegron had a maximum plasma concentration of 71.58 ng/mL in rats. Using metrics from green analytical chemistry and the RGB model scoring system, we compared the whiteness and greenness profiles of the published and suggested methods. The suggested method was found to be sensitive, eco-friendly, quick, cost-effective, and easy to use for estimation of mirabegron.

Optimization of Microwave-Assisted Polyphenol Extraction and Antioxidant Activity from Papaya Peel Using Response Surface Methodology and Artificial Neural Network

The objective of the present study is to determine the optimal conditions of microwave-assisted extraction (MAE) such as microwave power (MWP), irradiation time (I-time), ethanol concentration (EtOH%), and solvent-to-solid ratio (S/S) for maximizing total polyphenol content (TPC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity from papaya peel. Box-Behnken design (BBD) was used considering MWP 300–600 W, I-time 60-120 s, EtOH% 30-70%, and S/S 30-70 mL/g. Additionally, response surface methodology (RSM) and artificial neural networks (ANN) were employed for modelling, with cross-validation to enhance reliability. These models were combined with the desirability function (DF) and/or genetic algorithm (GA) optimization approaches. Maximizing TPC and DPPH activity while maintaining MWP, I-time, EtOH%, and S/S within their respective ranges using hybrid optimization approaches (RSM-DF: TPC = 1058 mgGAE/100g, and DPPH = 83%, RSM-GA: TPC = 1064 mgGAE/100g and DPPH = 79%, and ANN-GA: TPC = 1086 mgGAE/100g, and DPPH = 83%,) yielded consistent optimal results. An additional optimization approach (RSM-DF: TPC = 955 mgGAE/100g, and DPPH = 90%), aimed at minimizing MWP, I-time, EtOH%, and S/S while maximizing TPC and DPPH activity, showed a significant reduction of approximately 3 L in ethanol consumption for each 100 g of dry samples. The maximized TPC and DPPH activity in all four approaches showed a significant (p < 0.05) alignment with their corresponding validation tests, demonstrating the better performance of these modelling and optimization processes. In terms of assessing the effectiveness of microwave assistance, conventional solvent extraction was also performed, maintaining a 70 mL/g S/S ratio of 55% ethanol at 60°C for 2 h. This method resulted in lower values of TPC (857 ± 23 g GAE/100g) yield and DPPH activity (72 ± 5%) compared to the optimized condition of MAE.