Everolimus is a drug approved for the treatment of breast cancer with HR+ and advanced breast cancer reoccurring in postmenopausal women. The oral administration of EVE has been observed to have low oral bioavailability and severe epithelial cutaneous events that include rashes and lip ulceration followed by mouth ulceration after oral administration.
The present research aimed to enhance the bioavailability by loading the EVE into a stealth liposomal formulation (S-EVE-LIPO) intended for intravenous administration.
The surface of the liposomes was modified with vitamin E TPGS, which prolongs the systemic circulation of the drug and provides additional benefits like inhibition of the P-gp efflux pump and acting synergistically with EVE.
The formulation was prepared using the thin film hydration method and optimized using a D-optimal mixture design. ANOVA suggested the significance of the proposed mathematic model, and the optimized formulation was generated by design expert software. The optimized formulation (S-EVE-LIPO) was observed with nanometric size (99.5 ± 3.70 nm) with higher encapsulation efficacy (81.5 ± 2.86 %). The S-EVELIPO formulation indicated a sustained release profile as 90.22% drug release was observed in 48 h, whereas the formulation without vitamin E TPGS (EVE-LIPO) released only 74.15 drugs in 24 hours. In vitro cytotoxicity study suggested that the presence of vitamin E TPGS lowers the IC50 value (54.2 ± 1.69), increases the cellular uptake of the formulation, also increases the generation of ROS, and shows better hemocompatibility.
Vitamin E TPGS could be set as a vital additive to improve therapeutic efficacy and reduce offsite toxicity and dosing frequency.

Potassium citrate (KC) and potassium lactate (KL) are considered as salt replacers due to their saltiness, processing advantages, and health benefits. However, the obvious bitter taste associated with these compounds has limited their use in salt substitutes. Despite this challenge, little attention has been paid to improving their sensory properties. This study provided evidence that dietary polysaccharide carrageenan can effectively mask the bitterness of KC and KL by specifically binding K+ and forming double helix chains. A highly accurate prediction model was then established for the saltiness and bitterness of low-sodium salts using mixture design principles. Three low-sodium salt formulas containing different potassium salts (KC, KL, KCl), NaCl, and carrageenan were created based on the prediction model. These formulas exhibited favorable saltiness potencies (>0.85) without any noticeable odor, preserving the sensory characteristics of high-sodium food products like seasoning powder while significantly reducing their sodium content. This research provides a promising approach for the food industry to formulate alternative low-sodium products with substantially reduced sodium content, potentially contributing to decreased salt intake.

Recognizing the challenges in using botanicals as sustainable pest control agents due to compositional variation, this study addresses the limitations of traditional component-based approaches such as Hewlett and Plackett or Wadley\'s models. Based on the assumption of noninteractivity among constituents, these models often fail to predict outcomes accurately due to dynamic intermolecular interactions. We introduce a whole mixture-based approach, employing a combination of experimental design and polynomial modeling. This technique accurately predicts miticidal activity on Tetranychus urticae, ecotoxicity on Daphnia magna, and phytotoxic activities on Phaseolus vulgaris of Rosemarinus officinalis essential oils with varying composition. The RMSE values from the polynomial model are 66.9 and 5.0 for miticidal activity and ecotoxicity, respectively, while they are much higher in component-based models, up to 1097.7 and 41.3, respectively. Additionally, we utilize multiobjective optimization algorithms to identify the optimal supplementary blending of oils and compounds. This strategy aims to maximize miticidal effectiveness while minimizing ecotoxicity and phytotoxicity. Our approach for predicting multicomponent mixture effects is likely to bridge the knowledge gap between research and commercialization.

In the present study, an initial screening was conducted using 12 types of cell culture media, and four media with the best performance were selected for further study. The optimization of four media blend for YFV production was evaluated using an Augmented simplex centroid mixture design. Among all the different models that were investigated, the quadratic model was found to be the most appropriate model for exploring mixture design. It was found that M10 exhibited the greatest impact on YFV production, followed by M9, M4, and M1. The utilization of M1 and M4 media individually yielded higher compared to their blends with other media. The YFV titers were reduced when M1 media was combined with other media. The utilization of M9 and M10 media in combination resulted a higher viral yield compared to their respective concentrations. The optimal ratio for achieving a higher titer of YFV from primary CEFs was found to be approximately 38:62, with M9 and M10 being the most favorable media blend. The use of a media mixture led to a significant increase of virus titer up to 2.6 × 108 PFU/ml or 2 log titer yield, which is equivalent to 1.92 × 105 doses, without any changes to growth conditions or other process factors. This study concluded that the utilization of a mixture design could be efficiently employed to choose the optimal combination of media blends for enhanced viral production from cell culture.

Seed coating ensures the targeted delivery of various compounds from the early stages of development to increase crop quality and yield. Silicon and alginate are known to have plant biostimulant effects. Rice husk (RH) is a significant source of biosilica. In this study, we coated mung bean seeds with an alginate-glycerol-sorbitol (AGS) film with embedded biogenic nanosilica (SiNPs) from RH, with significant plant biostimulant activity. After dilute acid hydrolysis of ground RH in a temperature-controlled hermetic reactor, the resulting RH substrate was neutralized and calcined at 650°C. The structural and compositional characteristics of the native RH, the intermediate substrate, and SiNPs, as well as the release of soluble Si from SiNPs, were investigated. The film for seed coating was optimized using a mixture design with three factors. The physiological properties were assessed in the absence and the presence of 50 mM salt added from the beginning. The main parameters investigated were the growth, development, metabolic activity, reactive oxygen species (ROS) metabolism, and the Si content of seedlings. The results evidenced a homogeneous AGS film formation embedding 50-nm amorphous SiNPs having Si-O-Si and Si-OH bonds, 0.347 cm3/g CPV (cumulative pore volume), and 240 m2/g SSA (specific surface area). The coating film has remarkable properties of enhancing the metabolic, proton pump activities and ROS scavenging of mung seedlings under salt stress. The study shows that the RH biogenic SiNPs can be efficiently applied, together with the optimized, beneficial alginate-based film, as plant biostimulants that alleviate saline stress from the first stages of plant development.

The synergistic effects of essential oils (EOs) from three aromatic plant species, Foeniculum vulgare subsp. piperitum (C.Presl) Bég. (FV), Origanum heracleoticum L. (OH) and Lavandula austroapennina N.G.Passal., Tundis & Upson. (LA), were evaluated for their inhibitory properties on nitric oxide production in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). We utilized a Design of Experiments (DoE) methodology to optimize a formulation by combining three Essential Oils (EOs), while simultaneously taking into account two response variables, maximization of NO inhibition with minimum cytotoxicity. The optimal blend of components was predicted, and the statistical outcome\'s efficacy was experimentally verified. The combination corresponding to 87.7 % FV, 12.3 % LA and 0.0 % OH showed high inhibitory effect (76.3 %) with negligible cytotoxicity (4.5 %). This research provides new information on the interactions among fennel, oregano and lavender essential oils and shows how they can synergistically inhibit in vitro LPS-induced NO production.

The study endeavors the fabrication of extended-release adipic acid (APA) buccal films employing a quality by design (QbD) approach. The films intended for the treatment of xerostomia were developed utilizing hot-melt extrusion technology. The patient-centered quality target product profile was created, and the critical quality attributes were identified accordingly. Three early-stage formulation development trials, complemented by risk assessment aligned the formulation and process parameters with the product quality standards. Employing a D-optimal mixture design, the formulations were systematically optimized by evaluating three formulation variables: amount of the release-controlling polymer Eudragit® (E RSPO), bioadhesive agent Carbopol® (CBP 971P), and pore forming agent polyethylene glycol (PEG 1500) as independent variables, and % APA release in 1, 4 and 8 h as responses. Using design of experiment software (Design-Expert®), a total of 16 experimental runs were computed and extruded using a Thermofisher ScientificTM twin screw extruder. All films exhibited acceptable content uniformity and extended-release profiles with the potential for releasing APA for at least 8 h. Films containing 30% E RSPO, 10% CBP 971P, and 20% PEG 1500 released 88.6% APA in 8 h. Increasing the CBP concentration enhanced adhesiveness and swelling capacities while decreasing E RSPO concentration yielded films with higher mechanical strength. The release kinetics fitted well into Higuchi and Krosmeyer-Peppas models indicating a Fickian diffusion release mechanism.

Gluten-free bakery products are the definitive solution for people with celiac disease and gluten sensitivity. In this study, the production of gluten-free sponge cake was optimized using a mixture design methodology. Effects of the amount of ingredients, including quinoa (Chenopodium quinoa) (6-10 g), oleaster (Eleagnus Angustifolia) (1-2 g), and pumpkin powder (Cucurbita moschata) (1-4 g) on the physicochemical characteristics and sensory qualities (color, flavor, cutability, texture, appearance, and overall acceptability) of cakes were investigated. Significant regression models that explained the effects of different amounts of flour on all response variables were determined. The proposed model in this study had high R2 and R2 (adj). Therefore, the model was approved for fitting information. Finally, a gluten-free sponge cake recipe was formulated using 1 g of oleaster flour, 1 g of pumpkin, and 10 g of quinoa flour to achieve the desired sensory quality.

The thermal stability of polyurethanes, known for its limitations, was addressed in this research by seeking improvement through the introduction of carbohydrate-based chain extenders. In this research paper, we systematically sought to improve the thermal resistance of polyurethanes by incorporating carboxymethyl cellulose and chitosan, representing a pioneering application of the mixture design approach in their preparation. In this synthesis, hydroxyl-terminated polybutadiene and isophorone diisocyanate (IPDI) were reacted to prepare -NCO terminated prepolymer, which was subsequently reacted with varying mole ratios of CMC and CSN to develop a series of five PU samples. The prepared PU samples were characterized using the Fourier-transformed infrared spectroscopic technique. Thermal pyrolysis of PU samples was examined using thermal gravimetric analysis (TGA). It was observed that, among all the samples, PUS-3 showed remarkable thermal stability over a wide temperature range. A comprehensive statistical analysis was conducted to substantiate the experimental findings. It was estimated that CMC and CSN significantly enhance the thermal stability of the samples when involved in an interaction fashion. The ANOVA Table for the mixture design demonstrates that over 90 % of the total variation in thermal stability is explained by the mixture model across a wide temperature range. Moreover, PSU-3 exhibited 4 % more thermal stability over a wide range of temperatures on average, as compared to contemporary samples.

Curcumin, a vital bioactive compound found naturally, has diverse biological applications. However, a major limitation of curcumin is its low bioavailability caused by its limited solubility in water. Hence, it is possible to overcome this problem through preparing oil in water nanodispersion of curcumin that emulsifier can play key role to produce nanodispersion. In the present study, the effect of three emulsifiers of Tween 80, Arabic Gum and Polyethylene glycol on preparing nanodispersions with desirable properties was investigated using subcritical water method and a mixture design. Zeta-potential and particle size of the achieved nanodispersions were taken into account as outcome factors. The optimum values for emulsifiers of Tween 80, Arabic Gum and Polyethylene glycol were obtained as 0.588 g, 0.639 g and 0.273 g, respectively, using the suggested model, so that obtained nanodispersion had minimum particle size (101.89 nm) and maximum zeta-potential (-24.99 mV). In fact, 102.5 nm and - 24.7 mV were obtained from experimental data at these values of emulsifiers. In addition, maximum loading potential (0.199 g/L), efficiency (99.5%), and minimum total curcumin loss (0.5%) were acquired at these optimum values. The results also show that the nanodispersion had a powerful antioxidant activity (65.27%) with extra antibacterial activity in facing with both E. coli and S. aureus strains. Moreover, curcumin nanodispersion was significantly taken up by HT-29 cells and resulted in the production of oxidative stress in the cells, leading to a decrease in the growth of cancer cells.