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Response Surface Methodology for Statistical Optimization of Chitosan/Alginate Nanoparticles as a Vehicle for Recombinant Human Bone Morphogenetic Protein-2 Delivery
In this study, chitosan/alginate nanoparticles are prospected as a carrier for controlled release of recombinant human bone morphogenetic protein-2 (rhBMP-2).
The rhBMP-2-loaded chitosan/alginate nanoparticles (Cs/Alg/B NPs) were prepared using the ionic gelation (IG) method. The current research was conducted to optimize the effective factors for entrapping rhBMP-2 in Cs/Alg NPs using response surface methodology (RSM) and the Box-Behnken design (BBD). The variables were the Cs/Alg molecular weight (Mw) ratios (1-3), pH (4.8-5.5), stirring rates (900-1300 rpm) and the responses included size, ζ-potential, polydispersity index (PDI), loading efficacy (LE), cumulative release (CR), and morphological degradation time (MDE). Then, the morphological properties of optimum formulation were studied for post-characterization. In the next step, the MTT assay for the optimized run was done for 24 and 48 hours.
The results revealed that the optimum conditions for the mentioned variables were stirring rate=1100 rpm, pH=5.15, and Cs/Alg Mw ratio=1.75 based on numerical optimization. It was shown that the average particle size and loading efficacy at optimum conditions were 253 nm and 67%, respectively. Other responses were as follows: CR=66%, ζ-potential=+35mV, PDI=0.5, and MDT=7 days.
The results have suggested that the statistical optimization of rhBMP-2 offers the possibility of preparing Cs/Alg/B NPs with a favorable size, controlled release characteristics, and high loading efficiency. It is expected that the acquired optimum conditions will be useful for efficient rhBMP-2 delivery.
Journal Article
Box–Behnken Design for Polycarbonate-Pigment Blending: Applications and Characterization Techniques
Incorporating pigments into polymers can be done for various purposes, including the introduction of color, interfacial effects, or aesthetics. If these pigments are to disperse properly, then the process of extrusion must be optimized. During polymer compounding extrusion, three effective processing factors were investigated: feed rate (FR), speed (Sp.) and temperature (temp.) for a colored compounded polycarbonate (PC) grade (30/70%). The processing design techniques were obtained by applying design experiments in a response surface methodology (RSM) to blend two polycarbonates with pigments and optimize the processing temperatures at center points. The first study decided to utilize the response surface approach of Box–Behnken design (BBD) to design an experiment to optimize the process parameters. Statistical significance was demonstrated by the model passing all diagnostic tests. Furthermore, the three processing factors strongly impacted the characteristics of the tri-stimulus color, according to the results from a variance analysis. The second study identified process variables for the same PC grade at the center level, 25 kg/h FR, 750 rpm speed, and (255 °C) temp. The characterization and scanning morphology were examined using MicroCtscanner image analysis, SEM, DOM, rheology, FT-IR, and color-pigmented values were measured using a color spectrometer. The output response was significantly impacted when excellent color dispersion was observed with few agglomerates and less differences in colors at the center point. By characterizing these results and having good insight into color difference output and processing condition relationships, which have an adverse effect on color variation characteristics and minimize recycling compounds of different grades, results in cleaner environments benefits.
Journal Article
Repaglinide–Solid Lipid Nanoparticles in Chitosan Patches for Transdermal Application: Box–Behnken Design, Characterization, and In Vivo Evaluation
Repaglinide (REP) is an antidiabetic drug with limited oral bioavailability attributable to its low solubility and considerable first-pass hepatic breakdown. This study aimed to develop a biodegradable chitosan-based system loaded with REP-solid lipid nanoparticles (REP-SLNs) for controlled release and bioavailability enhancement via transdermal delivery.
REP-SLNs were fabricated by ultrasonic hot-melt emulsification. A Box-Behnken design (BBD) was employed to explore and optimize the impacts of processing variables (lipid content, surfactant concentration, and sonication amplitude) on particle size (PS), and entrapment efficiency (EE). The optimized REP-SLN formulation was then incorporated within a chitosan solution to develop a transdermal delivery system (REP-SLN-TDDS) and evaluated for physicochemical properties, drug release, and ex vivo permeation profiles. Pharmacokinetic and pharmacodynamic characteristics were assessed using experimental rats.
The optimized REP-SLNs had a PS of 249±9.8 nm and EE of 78%±2.3%. The developed REP-SLN-TDDS demonstrated acceptable characteristics without significant aggregation of REP-SLNs throughout the casting and drying processes. The REP-SLN-TDDS exhibited a biphasic release pattern, where around 36% of the drug load was released during the first 2 h, then the drug release was sustained at around 80% at 24 h. The computed flux across rat skin for the REP-SLN-TDDS was 2.481±0.22 μg/cm
/h in comparison to 0.696±0.07 μg/cm
/h for the unprocessed REP, with an enhancement ratio of 3.56. The REP-SLN-TDDS was capable of sustaining greater REP plasma levels over a 24 h period (
<0.05). The REP-SLN-TDDS also reduced blood glucose levels compared to unprocessed REP and commercial tablets (
<0.05) in experimental rats.
Our REP-SLN-TDDS can be considered an efficient therapeutic option for REP administration.
Journal Article
The utilization of microwaves in revitalizing peroxymonosulfate for tetracycline decomposition: optimization via response surface methodology
Antibiotic contamination in water has received significant attention in recent years for the reason that the residuals of antibiotics can promote the progression of antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs). It is difficult to treat antibiotics using conventional biological treatment methods. In order to investigate an efficient new method of treating antibiotics in water, in this study, microwave (MW) was employed in revitalizing peroxymonosulfate (PMS) to treat typical antibiotic tetracycline (TC). The Box–Behnken design (BBD) was applied to organize the experimental schemes. The response surface methodology (RSM) optimization was run to derive the best experimental conditions and validated using actual data. Moreover, the main mechanisms of PMS activation via MW were resolved. The results demonstrated that the relationship between TC removal rate and influencing factors was consistent with a quadratic model, where the P-value was less than 0.05, and the model was considered significant. The optimal condition resulting from the model optimization were power = 800 W, [PMS] = 0.4 mM, and pH = 6.0. Under such conditions, the actual removal of TC was 99.3%, very close to the predicted value of 99%. The quenching experiment confirmed that SO4•− and •OH were jointly responsible for TC removal.
Journal Article
Removal of Disperse Orange and Disperse Blue dyes present in textile mill effluent using zeolite synthesized from cenospheres
In this research, an efficient, ecofriendly method of using coal fly ash in the form of zeolite to treat wastewater containing dyes was studied. Response surface methodology involving Box–Behnken design was applied to a batch process to evaluate the effect of process parameters such as contact time, dye concentration, agitation speed, pH, and adsorbent dosage onto zeolite. Disperse Orange 25 (DO) dye showed a maximum of 96% removal under optimal conditions of contact time of 119 min, dye concentration of 38.00 mg/L, agitation speed of 158 rpm, pH of 6.10, and adsorbent dosage of 0.67 g/L, whereas 95.23% of Disperse Blue 79:1 (DB) dye removal was observed at adsorbent dose of 1.05 g/L, dye concentration of 26.72 mg/L, agitation speed of 145 rpm, pH of 5.68, and contact time of 122 min. It was concluded that cenosphere-derivatized zeolite adsorbent is efficient, ecofriendly, and economical and has high potential for the removal of DO and DB dyes from aqueous solutions.
Journal Article
Progressing Towards the Sustainable Development of Cream Formulations
This work aims at providing the assumptions to assist the sustainable development of cream formulations. Specifically, it envisions to rationalize and predict the effect of formulation and process variability on a 1% hydrocortisone cream quality profile, interplaying microstructure properties with product performance and stability. This tripartite analysis was supported by a Quality by Design approach, considering a three-factor, three-level Box-Behnken design. Critical material attributes and process parameters were identified from a failure mode, effects, and criticality analysis. The impact of glycerol monostearate amount, isopropyl myristate amount, and homogenization rate on relevant quality attributes was estimated crosswise. The significant variability in product droplet size, viscosity, thixotropic behavior, and viscoelastic properties demonstrated a noteworthy influence on hydrocortisone release profile (112 ± 2–196 ± 7 μg/cm2/√h) and permeation behavior (0.16 ± 0.03–0.97 ± 0.08 μg/cm2/h), and on the assay, instability index and creaming rate, with values ranging from 81.9 to 120.5%, 0.031 ± 0.012 to 0.28 ± 0.13 and from 0.009 ± 0.000 to 0.38 ± 0.07 μm/s, respectively. The release patterns were not straightforwardly correlated with the permeation behavior. Monitoring the microstructural parameters, through the balanced adjustment of formulation and process variables, is herein highlighted as the key enabler to predict cream performance and stability. Finally, based on quality targets and response constraints, optimal working conditions were successfully attained through the establishment of a design space.
Journal Article
Pomegranate extract-loaded solid lipid nanoparticles: design, optimization, and in vitro cytotoxicity study
Pomegranate extract (PE) is a natural product with potent antioxidant and anticancer activity because of its polyphenols content. The main purpose of this study was to maximize the PE chemotherapeutic efficacy by loading it in an optimized solid lipid nanoparticles (SLNs) formula.
The influence of independent variables, which were lipid concentration (X
), surfactant concentration (X
) and cosurfactant concentration (X
), on dependent ones, which were particle size (Y
), polydispersity index (Y
), zeta potential (Y
), entrapment efficiency (Y
) and cumulative % drug release (Y
), were studied and optimized using the Box-Behnken design. Fifteen formulations of PE-SLNs were prepared using hot homogenization followed by ultra-sonication technique. Response surface plots, Pareto charts and mathematical equations were produced to study the impact of independent variables on the dependent quality parameters. The anti-proliferative activity of the optimized formula was then evaluated in three different cancer cell lines, namely, MCF-7, PC-3 and HepG-2, in addition to one normal cell line, HFB-4.
The results demonstrated that the particle sizes ranged from 407.5 to 651.9 nm and the entrapment efficiencies ranged from 56.02 to 65.23%. Interestingly, the 50% inhibitory concentration of the optimized formula had more than a 40-fold improved effect on the cell growth inhibition in comparison with its free counterpart. Furthermore, it was more selective against cancer cells than normal cells particularly in MCF-7 breast cancer cells.
These data proved that nanoencapsulation of PE enhanced its anticancer efficacy. Therefore, our results suggested that a PE-loaded SLNs optimized-formula could be a promising chemo therapeutic agent.
Journal Article
Optimization of Microwave-Assisted Extraction of Polysaccharides from Ulva pertusa and Evaluation of Their Antioxidant Activity
The use of green marine seaweed Ulva spp. as foods, feed supplements, and functional ingredients has gained increasing interest. Microwave-assisted extraction technology was employed to improve the extraction yield and composition of Ulva pertusa polysaccharides. The antioxidant activity of ulvan was also evaluated. The impacts of four independent variables, i.e., extraction time (X1, 30 to 60 min), power (X2, 500 to 700 W), water-to-raw-material ratio (X3, 40 to 70), and pH (X4, 5 to 7) were evaluated. The chemical structure of different polysaccharides fractions was investigated via FT-IR and the determination of their antioxidant activities. A response surface methodology based on a Box–Behnken design (BBD) was used to optimize the extraction conditions as follows: extraction time of 43.63 min, power level of 600 W, water-to-raw-material ratio of 55.45, pH of 6.57, and maximum yield of 41.91%, with a desired value of 0.381. Ulvan exerted a strong antioxidant effect against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and showed reducing power in vitro. Ulvan protected RAW 264.7 cells against H2O2-induced oxidative stress by upregulating the expression and enhancing the activity of oxidative enzymes such as superoxide dismutase (SOD) and superoxide dismutase (CAT). The results suggest that the polysaccharides from U. pertusa might be promising bioactive compounds for commercial use.
Journal Article
Research on the development of nanocellulose based on agricultural waste and its processing and utilization in food sausages
Pepper cultivation generates over 50 million tons of straw waste annually, with a global utilization rate below 20%. To address this resource inefficiency and explore sustainable food additives, cellulose was extracted from discarded pepper stems (PS) (15-34.5% yield) via nitric acid - ethanol treatment, followed by nanocellulose synthesis through sulfuric acid hydrolysis (36.13% average yield). Characterization of nanocellulose was analyzed using scanning electron microscopy, Fourier-transform infrared, and X-ray diffraction analysis. It was found through mice experiments that intaking nanocellulose-containing sausages could significantly reduce the food intake of mice, inhibit the weight growth of mice, and significantly improve the strength of the skeletal muscles of mice. This research provides a basis for subsequent studies on the efficient recycling of PS and the application of nanocellulose as a food additive in food processing.
Journal Article