Box-Behnken Statistical Design Research Articles

Chemical recycling of post-consumer poly(ethylene terephthalate) (PET) driven by the protic ionic liquid 2-HEAA: Performance, kinetics and mechanism

The circular economy is a paradigm for the upcoming industrial era, in which plastic wastes must be focused on as new resources. Chemical valorisation permits deepening into waste-to-gate schemes by obtaining new chemical platforms to be reintroduced in the production market. In this context, the potential of the protic ionic liquid 2-hydroxyethyl ammonium acetate (2-HEAA) to be used as a homogeneous catalytic co-solvent for the glycolytic conversion of post-consumer poly(ethylene terephthalate) (PET) was validated from different perspectives. Studies were performed for the reaction triplet framed under the experimental conditions (i) temperature T [160,170,180 ºC], (ii) plastic-to-solvent mass ratio P/S [1:3, 1:4,1:5] and (iii) plastic-to-ionic liquid mass ratio P/IL [2:1, 2:2, 2:3]. The reaction was confirmed in terms of the transformation of PET into BHET (bis(2-hydroxyethyl terephthalate) and a proposal of mechanism induced by the amine group of the 2-HEAA is given. The thermal kinetics were modelled and a first-order equation and an apparent activation energy of 60.5 kJ·mol-1 were obtained. A statistical Box-Behnken design of experiments explained the relationship between the factors of the glycolysis triplet by a response surface, with a maximum around {T = 170 ºC, P/S = 1:3.75 and P/IL = 2:1.75}, being T and P/S statistically relevant, whereas only the presence of 2-HEAA and not its amount P/IL was significant. Finally, the reusability of 2-HEAA after 90-min glycolytic chemical valorisations was confirmed up to 4 cycles. The results position 2-HEAA as a promising catalytic co-solvent for the scale-up of chemical valorisation of PET.

Production of kojic acid by Aspergillus flavus OL314748 using box-Behnken statistical design and its antibacterial and anticancer applications using molecular docking technique

Kojic acid is a wonderful fungal secondary metabolite that has several applications in the food, medical, and agriculture sectors. Many human diseases become resistant to normal antibiotics and normal treatments. We need to search for alternative treatment sources and understand their mode of action. Aspergillus flavus ASU45 (OL314748) was isolated from the caraway rhizosphere as a non-aflatoxin producer and identified genetically using 18S rRNA gene sequencing. After applying the Box-Behnken statistical design to maximize KA production, the production raised from 39.96 to 81.59 g/l utilizing (g/l) glucose 150, yeast extract 5, KH2PO4 1, MgSO4.7H2O 2, and medium pH 3 with a coefficient (R2) of 98.45%. Extracted KA was characterized using FTIR, XRD, and a scanning electron microscope. Crystalized KA was an effective antibacterial agent against six human pathogenic bacteria (Bacillus cereus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, Serratia marcescens, and Serratia plymuthica). KA achieves high inhibition activity against Bacillus cereus, K. pneumonia, and S. plymuthica at 100 μg/ml concentration by 2.75, 2.85, and 2.85 compared with chloramphenicol which gives inhibition zones 1, 1.1, and 1.6, respectively. Crystalized KA had anticancer activity versus three types of cancer cell lines (Mcf-7, HepG2, and Huh7) and demonstrated high cytotoxic capabilities on HepG-2 cells that propose strong antitumor potent of KA versus hepatocellular carcinoma. The antibacterial and anticancer modes of action were illustrated using the molecular docking technique. Crystalized kojic acid from a biological source represented a promising microbial metabolite that could be utilized as an alternative antibacterial and anticancer agent effectively.

Effects of Fe3O4 magnetic nanoparticles on nitrate removal efficiency: an optimization study using response surface methodology

ABSTRACT The nitrate contamination of water resources is a serious environmental problem, which may be solved by nitrate sorption onto magnetic nanoparticles. In this study, the effects of Fe3O4 magnetic nanoparticles on nitrate removal were investigated. Fe3O4 was synthesized by a co-precipitation method and used as an adsorbent for nitrate removal. pH, adsorbent dosage, and contact time were considered as the main variables. The effective ranges of these variables were chosen as pH = 4–10, adsorbent dose = 0.5–1.5 g/L, and contact time = 30–90 min. The optimization study was conducted using the Box–Behnken statistical design method. According to the analysis of variance table, it can be concluded that the model is ‘significant’ and the value of R2 was 0.99. The results of the study show that the maximum nitrate removal efficiency was about 91.02%. This was obtained at pH 7, using a dose of 1.3 g/Lof Fe3O4, and a contact time of 28 min.

ENHANCED SURFACE QUALITY AND STRENGTH OF FDMed SPECIMENS USING BBD AND BIO-INSPIRED ALGORITHMS

This research investigated and optimized the parameters of the FDM process by employing bio-inspired algorithms for determining the optimal parameter settings in terms of surface quality and mechanical performance. Four important process parameters including layer thickness (0.11–0.33[Formula: see text]mm), part orientation (0–90∘), raster width (0.2–0.56[Formula: see text]mm), and the raster angle (0–60∘) at three variation levels were selected for fabricating the specimens (ABS material P430) using the statistical Box–Behnken design. ANOVA analysis and multiple regression analysis were used to fit the experimental data to a second-order polynomial equation. Through, the RSM analysis, the layer thickness is the key important factor that accounts for all of the responses. The fracture behavior of specimens was examined using a scanning electron microscope (SEM). From the SEM analysis, a substantial amount of plastic deformation on the fracture surface indicative of craze cracking is visible from a 0∘ orientation, indicating a totally ductile fracture mechanism. Then, three swarm intelligence algorithms such as Tasmanian Devil Optimization (TDO), Remora Optimization Algorithm (ROA), Tuna Swarm Optimization (TSO) were implemented to optimize the input parameters that would lead to minimum surface roughness and maximum tensile strength. Experimental data and predicted values varied between 1.64% and 1.84%, as shown by verification experiments.

Valorization of sugarcane bagasse cellulose to synthesize novel graphene oxide-based composite for remediation of atrazine – Optimization studies

Atrazine (AZE) is a hazardous herbicide that pollutes drinking water and wastewater at an alarming rate, posturing a somberhazard to the environment and human being. This research is aimed to investigate the valorization of biomass for the synthesis and applicationof novel Sugarcane Bagasse Cellulose (SCBC) - Graphene oxide (GO) nanocomposite for remediation of atrazine. The novel nanocomposite is characterized using Fourier transform infrared spectroscopy (FTIR), Particle size distribution, Raman spectra analysis, X-ray analysis (XRD), Scanning electron microscope analysis (SEM) and Transmission electron microscopy (TEM). The prepared GOSCBC had high surface area of 189 m2/g, pore volume of 0.13 cm3/g, and inter-particle pore width of 17 nm. The impact of operating constraints such as adsorbent dose (50–150 mg), medium pH (4.5–8.5), contact period (3 h), temperature (15–45°C), and atrazine concentration (10–50 mg/L) were varied and optimum conditions were examined with the help of Box-Behnken statistical design (BBD). The optimum conditions identified were: 90.84 mg/L nanocomposite; pH 5.51; time 180 min; temperature 34.64°C and feed concentration 27.77 mg/L. The adsorption statistical analyses were performed and the values were determined using the isotherms and kinetic models; the optimal parameters were evaluated using sum of normalised errors approach. The maximum adsorption capacity of AZE was found to be 143.29 mg/g. The mechanism of sorption is well represented by PSO model. The exothermic nature of removal process was confirmed through thermodynamic parameters. The reusability of the nanocomposite was identified to be efficient for six cycles.

Development and optimization of kaempferol loaded ethosomes using Box-Behnken statistical design: In vitro and ex-vivo assessments.

Kaempferol (KMP) belong to flavonoid class have developed in ethosomal formulation and were evaluated for their potential to treat diabetic foot ulcers. Even though ethosomes are highly deformable, they can pass through human skin intact. KMP ethosomes were formulated using the cold method and optimized by Box-Behnken design (BBD) (three-factor, three-level (33 )). The formulation variables used for optimization are drug concentration of KMP, soylecithin content, and ethanol percentage. The optimized formulation was examined using transmission electronic microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, in-vitro release, ex-vivo permeation studies, and storage stability. The optimized KMP ethosomes was found to have vesicle size (VS) of 283 ± 0.3 nm and zeta potential (ZP) of -29.67 ± 0.3 mV, polydispersity index (PDI) of 0.36, % entrapment efficiency (%EE) of 91.02 ± 0.21%, drug loading (%) of 46.23 ± 2.5% followed by good storage stability at 4°C/60 ± 5% RH. In vitro drug release of optimized KMP ethosomes was 88.2 ± 2.75%, which was approximately double when compared with pure KMP release, that is 49.9 ± 1.89%. The release kinetics for optimized KMP ethosomes follows the Korsmeyer-Peppas model. An apparent permeation coefficient of 356.25 ± 0.5 μg/cm2 was determined and compared with pure KMP (118.46 ± 0.3 μg/cm2 ) for 24 h. According to the study, ethosomes can be a cutting-edge strategy that offers a new delivery method for prolonged and targeted distribution of KMP in a variety of dosage forms including oral, topical, transdermal, and so forth.

Carbon and nitrogen optimization in solid-state fermentation for sustainable sophorolipid production using industrial waste.

The use of alternative feedstocks such as industrial or food waste is being explored for the sustainable production of sophorolipids (SLs). Microbial biosurfactants are mainly produced via submerged fermentation (SmF); however, solid-state fermentation (SSF) seems to be a promising alternative for using solid waste or byproducts that could not be exploited by SmF. Applying the advantages that SSF offers and with the aim of revalorizing industrial organic waste, the impact of carbon and nitrogen sources on the relationship between yeast growth and SL production was analyzed. The laboratory-scale system used winterization oil cake as the solid waste for a hydrophobic carbon source. Pure hydrophilic carbon (glucose) and nitrogen (urea) sources were used in a Box-Behnken statistical design of experiments at different ratios by applying the response surface methodology. Optimal conditions to maximize the production and productivity of diacetylated lactonic C18:1 were a glucose:nitrogen ratio of 181.7:1.43(w w-1 based on the initial dry matter) at a fermentation time of 100h, reaching 0.54 total gram of diacetylated lactonic C18:1 with a yield of 0.047g per gram of initial dry mass. Moreover, time course fermentation under optimized conditions increased the SL crude extract and diacetylated lactonic C8:1 production by 22% and 30%, respectively, when compared to reference conditions. After optimization, industrial wastes were used to substitute pure substrates. Different industrial sludges, OFMSW hydrolysate, and sweet candy industry wastewater provided nitrogen, hydrophilic carbon, and micronutrients, respectively, allowing their use as alternative feedstocks. Sweet candy industry wastewater and cosmetic sludge are potential hydrophilic carbon and nitrogen sources, respectively, for sophorolipid production, achieving yields of approximately 70% when compared to the control group.

Fabrication of architectonic nanosponges for intraocular delivery of Brinzolamide: An insight into QbD driven optimization, in vitro characterization, and pharmacodynamics

The intricate structure of the eye poses difficulties in drug targeting, which can be surmounted with the help of nanoformulation strategies. With this view, brinzolamide nanosponges (BNS) were prepared using the emulsion solvent evaporation technique and optimized via Box-Behnken statistical design. The optimized BNS were further incorporated into a poloxamer 407 in situ gel (BNS-ISG) and evaluated. The optimized BNS showed spherical morphology, entrapment efficiency of 83.12±1.2% with particle size of 114±2.32 nm and PDI of 0.11±0.01. The optimized BNS-ISG exhibited a pseudoplastic behavior and depicted a gelling temperature and gelation time of 35±0.5°C and 10±2 s respectively. In-vitro release and ex- vivo permeation studies of BNS-ISG demonstrated a sustained release pattern as compared to Brinzox®. Additionally, the HET-CAM and in vitro cytotoxicity studies (using SIRC cell line) ensured that the formulation was non-irritant and nontoxic for ophthalmic delivery. The in vivo pharmacodynamic study using rabbit model depicted that BNS-ISG treatment significantly lowers the intra ocular pressure for prolonged period of time when compared with Brinzox®. In conclusion, the BNS-ISG is an efficient and scalable drug delivery system with significant potential as the targeted therapy of posterior segment eye diseases.

The Optimization of Operating Conditions in the Cross-Flow Microfiltration of Grape Marc Extract by Response Surface Methodology.

The recovery of valuable compounds like phenolic compounds and sugars from grape marc extracts implies different steps, including clarification. In this study, a response surface methodology (RSM) was used as a statistical tool to study the effects of operating conditions such as transmembrane pressure (TMP), temperature and feed flow rate on the performance of a microfiltration (MF) monotubular ceramic membrane with a pore size of 0.14 μm in the clarification of grape marc extract from the Carménère variety, as well to optimize the process conditions by implementing the Box-Behnken statistical design. The desirability function approach was applied to analyze the regression model equations in order to maximize the permeate flux and concentration of malvidin-3-O-glucoside, glucose and fructose in the clarified extract. The optimal operating conditions were found to be 1 bar, 29.01 °C and 5.64 L/min. Under these conditions, the permeate flux and concentration of malvidin-3-O-glucoside, glucose and fructose resulted in 65.78 L/m2h, 43.73 mg/L, 305.89 mg/L, and 274.85 mg/L, respectively.

Optimizing the removal of iron oxide from Egyptian feldspar ore

The demand for feldspar as a raw material for various industrial applications continuously increases. Feldspar is a primary raw material in manufacturing ceramics, glass, fillers, welding electrodes, and enamel. Feldspar is often associated with iron oxide, which decreases its economic value and hinders its industrial application. The present work aimed at reducing iron oxide content in Egyptian feldspar ore from the Wadi Zerabi locality. Ball milling was used for preparing feldspar feed of size -250+45µm. Carpco dry high-intensity magnetic separation followed by acid leaching processes were carried out in order to decrease the iron contamination and increase the feldspar content. A Box-Behnken statistical design was used to optimize the magnetic separation results. From a feldspar feed containing 1.40% Fe2O3, a non-magnetic concentrate of 0.25% Fe2O3 was obtained. The Fe2O3 removal reached up to 82% with a high yield as the % weight of non-magnetic feldspar reached up to 97.5%. The leaching process further reduced the iron oxide content down to 0.19 %. Also, the feldspar whiteness was improved from 65.17% in the original ore to 85.60% in the leached product.

A pedagogical approach for the development and optimization of a novel mix of biowastes-derived hydroxyapatite using the Box-Behnken experimental design

The current study details the creation of synthetic hydroxyapatite (HAp) using a combination of catfish and bovine bones (C&B). This is done to design the optimum processing parameters and consolidate instructional strategies to develop HAp scaffolds for biomedical engineering. The HAp produced from the novel mix of the biogenic materials (C&B) was through calcination and supported with the sol-gel technique, sintering, and low-cold compaction pressure. The ideal preparation conditions were identified with the aid of the Box-Behnken statistical design in response surface methodology. To understand the physicochemical and mechanical properties of the formulation, analytical studies on the synthesized HAp were carried out. To establish a substantial relation between the physicomechanical properties of the produced HAp scaffolds, three parameters— sintering temperature, compaction loads, and holding times were used. In the evaluation, the sintering temperature was found to have the greatest impact on the material's physicomechanical properties, with compressive strength (13 MPa), porosity (49.45 %), and elastic modulus (2.216 GPa) being the most enhanced properties in that order. The physicomechanical characteristics of the HAp scaffolds were at their optimal at 900 °C, 1 h 18 min of holding time, and 311.73 Pa of compaction pressure. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) results showed that powders with a dominant HAp phase were produced at all runs, including the optimum run. Therefore, using a computationally effective methodology that is helpful for novelties in biomedical engineering education, this study demonstrates the optimal process for the synthesis of a novel matrix bone-derived HAp, showing the most significant relations liable for manufacturing medically suitable HAp scaffolds from the mixture of bovine and catfish bones.

Quality by Design Approach for Development and Characterization of Granisetron Hydrochloride-Loaded Orodispersible Films

AbstractGranisetron hydrochloride can be used to prevent and treat nausea and vomiting induced by chemotherapy. Its prolonged half-life and reduced dose requirement improve patient acceptance. However, patients undergoing chemotherapy often suffer from dysphagia and drug spitting due to emesis. Hence, the development of a patient-centered formulation of granisetron hydrochloride with simple medication and high compliance is crucial. The current study employed a polymer combination of polyvinylpyrrolidone/polyvinyl alcohol (PVP/PVA) as film-forming materials and Lycoat® RS 780 as a disintegrant to formulate orodispersible films (ODFs) loaded with granisetron hydrochloride. Guided by the concept of quality by design, the quality target product profile and critical quality attributes (CQAs) for the ODF were defined. Through the quality risk assessment, essential factors that have a significant impact on CQAs were identified. The formulation was screened using the Box–Behnken statistical design with three factors and three levels. Our data suggested that all ODF formulations exhibited a disintegration time of less than 60 seconds and complete dissolution within 5 minutes. Furthermore, the formulation displayed appropriate mechanical properties, water residue, and pH values. Thus, the granisetron hydrochloride-loaded ODF is regarded as a patient-friendly formulation that enhances compliance and consequently aids in therapeutic effectiveness.

Development and optimization of film forming non-pressurized liquid bandage for wound healing by Box-Behnken statistical design

The goal of the current investigation was to develop a non-pressurized liquid bandage to promote the healing of wounds by using silver sulfadiazine. A three-factor three level box-behnken statistical design was employed to optimize the drug-loaded liquid bandage. Film-forming liquid bandage was developed by using ethyl-cellulose, dibutyl sebacate, and glycerol. For optimization, ethyl cellulose, dibutyl sebacate, and isopropyl myristate were taken as independent variables while tensile strength, water vapor absorption value, and drying time were taken as dependent variables. The film-forming liquid bandage was evaluated for various parameters like tensile strength, water vapor absorption value, drying time, viscosity, pH, in-vitro drug release studies, in-vivo wound healing studies, and stability studies. The optimized formulation was found with the tensile strength of 68.24 ± 0.24 MPa, water vapor absorption value of 2.00 ± 0.25 %, drying time of 1.75 ± 0.14 min, viscosity of 60 ± 0.5 cPs, pH of 6.0 ± 0.5 and good physicochemical properties with satisfactory film-forming ability. The in-vitro study shows that the release of test formulations was better than the marketed formulation. After 6 h of study, the liquid bandage and marketed formulation showed 41.02 % and 29.32 % of drug release respectively. Significant results were obtained for the in-vivo wound healing studies. Upon comparison with the control group (2.61 mm) and marketed formulation (1.44 mm), rats treated with the optimized formulation exhibited a noticeable improvement in wound contraction (0.8 mm). The liquid bandage after three months of stability testing was found to be stable with optimum. The film-forming liquid bandage was found to be an effective alternative to conventional topical preparations as it develops a thin polymeric layer on the wound and the skin around it and improves comfort for the patient by protecting the wound from external factors and physical harm.

Optimization of the Hydrolysis Process of Microalgae Porphyridium cruentum Biomass with Variations of Hydrochloric Acid Concentration, Temperature, and Time using Response Surface Methodology (RSM)

Microalgae Porphyridium cruentum has potential as a raw material for bioethanol production because it has a high carbohydrate content. These carbohydrates can be broken down into reducing sugars through the hydrolysis process. The reducing sugar obtained will be used as a substrate in the production of bioethanol. This study aimed to produce a substrate with the best-reducing sugar indicator and to determine the optimum conditions for hydrolysis of P. cruentum microalgae biomass following the Box-Behnken statistical experimental design, using Response Surface Methodology (RSM). The parameters of the optimized hydrolysis process were HCl concentration (2 - 0.2 N), temperature (60 -120 ˚C), and hydrolysis time (30-180 min). The optimum conditions that have been achieved using RSM are an HCl concentration of 1.91 N, a temperature of 60 °C, and a hydrolysis time of 180 min were predicted a maximum total reducing sugar production of 810 mg/L. The experimental result of total reducing sugar obtained at optimum conditions was 895 mg/L, which was well close to the predicted value, verifying the appropriateness of the model.Abstract is informed about the statements of the problem, methods, scientific finding results and conclusion concisely

Binary Ethosomal Gel for Enhanced Transdermal Delivery of Tazarotene: Development, Refinement, in vitro Evaluation, and Skin Penetration Investigations

Background: Tazarotene (TZ) is a novel acetylenic class retinoid that selectively targets RARβ/γ. It is not particularly soluble or bioavailable, yet it is used to treat melanoma. Objective: To improve the tazarotene gel formula's transdermal distribution. Methods: TZ-incorporated binary ethosomes (TZ-BES) were developed for the current study. The cold technique and optimized Box-Behnken statistical design tools were used to synthesize the TZ-BES. The improved ethosome (TZ-BES13) was mixed with carbopol gel and tested for stability and ex vivo skin penetration, as well as viscosity, pH, spreadability, and drug content. Results: The optimal ethosomes (TZ-BES13) had a vesicle size of 168 nm, a PDI of 0.367, a zeta potential of -30 mV, and an entrapment effectiveness of 79.94%. TZ is enclosed in the ethosome matrix, as seen by the differential scanning calorimetry thermogram. FTIR shows that the TZ and additives are compatible. TZ-BES13-G2, the optimized TZ-BES13 gel, has a spreadability of 7.82 cm2, a pH of 6.52, a viscosity of 17235, and a drug content of 99.82±1.04%. Compared to the plan TZ-gel (43.54%), the TZ-BES13-G2 exhibits a much higher TZ release (89.22%). In 6 hours, rat abdomen skin permeability for TZ-BES13-G2 was 66.22±3.31%, much greater than that of plan TZ-gel (24.67%). The flow of TZ-BES13-G2 was 2.68 times greater than that of plan TZ-gel. The stability analysis showed that the formulation's properties had not changed significantly. Conclusion: Ethosomal gel offers an alternative mode of TZ administration when used topically.

Investigation into the influence of droplet size on the stability of diesel emulsions based on multiple light scattering

Diesel oil emulsification is a common method to enhance the coal slime flotation, but difficult to apply industrially due to its unstable characteristics. In this paper, based on the multiple light scattering technique and the statistical Box-Behnken design (BBD) tests, the effect of the process parameters such as shear speed (A), shear time (B), and the mass ratio of SDBS to Span80 (C) on turbiscan stability index (TSI) value was systematically studied, and the relationship between emulsion stability and emulsion droplet size was also explored. The results showed that the destabilization of emulsified diesel (ED) was related to gravity migration and an increase in droplet size and was well fitted by the classical first-order kinetic model with R2 > 0.99. The significant order in which the three factors negatively affect the TSI value is, shear speed (A) > the mass ratio of SDBS to Span80 (C) > shear time (B), with shear speed ranging from 1000 to 16000 rpm, with shear time from 10 to 15 min, and with ratio of Span 80/SDBS from 0.45 to 1.48, respectively. Analysis of variance (ANOVA) revealed a high R2 value of the regression model equation (R2 = 0.9857) and fitted to a second-order polynomial equation using multiple regression analysis. The representative particle size (D50) has a positive linear correlation with the TSI value, indicating the smaller the particle size, the more stable the ED. The theoretical analysis using the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory and Stokes-Richardson-Zaki model demonstrated that the smaller ED droplets have the greater energy barrier to overcome before coalescing and lower rising velocity to move to the upper oil phase, and hence better stability.

Optimizing biohydrogen production yields by employing locally isolated thermophilic bacteria from hot springs

A climate-neutral economy is anticipated to rely heavily on hydrogen because it enables emission-free transportation, heating, and manufacturing operations. Biohydrogen can be produced from various kinds of biological waste making the interest high. However, the yield and efficiency of the processes are still challenging. This study applied Box-Behnken statistical experimental design to investigate the influence of temperature (oC), pH, and CO volume (mL) together with the amount of Fe+2, Zn+2, and Ni+2 to enhance biohydrogen production yields from thermophilic cultures, both mixed and pure cultures isolated from hot springs in Izmir, Türkiye. The maximum H2 yields were reported as 0.13 mmolH2/mmolCO for mixed cultures, and the pure culture reached 2.5 fold higher yield (0.44 mmolH2/mmolCO). Bench-scale bioreactor with a custom-design micro sparger was successfully run for 7 days (highest 0.25 mmolH2/mmol CO). This is the first report in the literature with local isolates to demonstrate the optimization of H2 yields with a comparative approach, and scale-up in a 2 L bench scale bioreactor. The viability of using novel thermophilic isolates as biohydrogen producers was successfully proven.

Formulation and optimization of novel vesicular elastic carrier for transdermal delivery of lercanidipine for the treatment of hypertension

The blood pressure drug lercanidipine hydrochloride (LCP) is also prescribed to lower the risk of cardiovascular disease and heart attacks. However, it could be more bioavailable due to extensive first-pass metabolism. In this research study, bilosomes (BS) loaded with lercanidipine hydrochloride (BS-LCP) for transdermal drug delivery were developed and studied to increase bioavailability and patient compliance through high tissue penetration. The thin-film hydration method was used to formulate BS-LCP was optimized using Box-Behnken statistical design. Entrapment efficiency (%) was 82.36 ± 0.64%, mean vesicle size was 126.34 ± 1.28 nm, polydispersity index was 0.43 ± 0.1, and zeta potential was −52.74 ± 0.37 mV for the optimized bilosomal formulation. In 24 h, the amounts of LCP released from LCP-bilosomal preparation (BS-LCP) and LCP-bilosomal gel (BS-LCPG) were 97.53 ± 3.0% and 76.49 ± 4.0%, respectively. However, after 4 h, 98.724% was released from the LCP solution. Drug release from BS-LCPG was noticeably lower than that from LCP-bilosomes. The optimized BS-LCP vesicles were found to be perfectly round, with smooth surfaces and no aggregation, according to scanning electron microscopy (SEM) analysis. The Transmission electron microscopy (TEM) setup verified that the vesicles were round and had a restricted size distribution, indicating no irregularly shaped cysts were present. Inin-vitropermeation studies, bilosomal Gel (BSG) significantly outperformed the LCP solution and a commercially available formulation. Bilosomes are potential drug-delivery vesicles because they can avoid problems with the multiple-dose regime and limited oral bioavailability via the transdermal route.

Anti-Candida and Anti-Leishmanial Activities of Encapsulated Cinnamomum verum Essential Oil in Chitosan Nanoparticles.

Nanoencapsulation is widely considered as a highly effective strategy to enhance essential oils' (EO) stability by protecting them from oxidative deterioration and evaporation. The present study aims to optimize and characterize an efficient technique for encapsulating Cinnamomum (C.) verum essential oil into chitosan nanoparticles using response surface methodology (RSM). Moreover, the optimized C. verum EO nanoparticle was investigated for its antibacterial (against Gram-positive and Gram-negative bacteria), antifungal (against Candida albicans), and antiparasitic activity (against Leishmania parasites). Five parameters were investigated using a Plackett-Burman and Box-Behnken statistical design: the chitosan molecular weight, TPP concentration, C. verum EO/chitosan ratio, mixing method, and the duration of the reaction. Encapsulation efficiency and anti-candida activity were considered as responses. The antibacterial, anticandidal, and anti-leishmanial activities were also assessed using a standard micro-broth dilution assay and the cytotoxicity assay was assessed against the macrophage cell line RAW 264.7. The optimized nanoparticles were characterized using Fourier transform infrared spectroscopy, Zeta potential, and scanning electron microscopy. The study results indicated that under optimal conditions, the nanoencapsulation of C. verum EO into chitosan nanoparticles resulted in an encapsulation efficiency of 92.58%, with a regular distribution, a nanoparticle size of 480 ± 14.55 nm, and a favorable Zeta potential of 35.64 ± 1.37 mV. The optimized C. verum EO/chitosan nanoparticles showed strong antifungal activity against C. albicans pathogens (CMI = 125 µg mL-1), notable antibacterial activity against both Gram-positive and Gram-negative bacteria (ranging from 125 to 250 µg mL-1), high leishmanicidal potential against the promastigotes form of L. tropica and L. major (IC50 = 10.47 and 15.09 µg mL-1, respectively), and a four-fold cytotoxicity reduction compared to non-encapsulated essential oil. These results suggest that C. verum EO-loaded chitosan nanoparticles could be a promising delivery system for the treatment of cutaneous Candida albicans infections.

Dual Emerging Applications of Solid-State Fermentation (SSF) with Aspergillus niger and Ultrasonic-Assisted Extraction (UAE) for the Obtention of Antimicrobial Polyphenols from Pineapple Waste

The exploration of natural antimicrobial compounds is necessary due to the current bacterial resistance to synthetic antibiotics. For this reason, pineapple residues were evaluated as a natural source of phenolic compounds with antimicrobial capacity. Pineapple residues were fermented with A. niger GH1 and subjected to ultrasound for the extraction of phenolic compounds. In the solid-state fermentation (SSF), the peel and the core (70:30) were fermented for 32 h. Ultrasonic-assisted extraction (UAE) was optimized. The factors solid–liquid ratio (X1), ethanol concentration (X2), and extraction cycle (X3) were optimized through a Box–Behnken statistical design, using the total phenol content (TPC) as a response variable. The optimized and pre-purified extract with amberlite was characterized using HPLC-MS and we measured the antimicrobial activity against Listeria monocytogenes, Staphylococcus aureus, and Escherichia coli. The optimal values for X1, X2, and X3 were 82 mg/mL, 26%, and two cycles, respectively. The extract was effective as an antimicrobial agent against S. aureus and L. monocytogenes, with MICs of 50 mg/mL and 12.5 mg/mL, respectively; the bacterial growth curve and transmission electron microscopy (TEM) confirmed the antimicrobial activity. The main compounds identified in the antimicrobial extract were 3,4-DHPEA-EA, Phloretin 2′-O-xylosyl-glucoside, and Feruloyl tartaric acid. Overall, the combination SSF-UAE showed to be a promising strategy to recover phenolic compounds from pineapple residues, exhibiting great potential as a natural antimicrobial agent.