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Nanostructured lipid carriers (NLCs) are typically composed of liquid lipids, solid lipids, and surfactants, enabling the encapsulation of lipophilic drugs. Butamben is a Class II anesthetic drug, according to the Biopharmaceutical Classification System (BCS); it has a log P of 2.87 and is considered a 'brick dust' (poorly water-soluble and poorly lipid-soluble) drug. This characteristic poses a challenge for the development of NLCs, as they are not soluble in the liquid lipid present in the NLC core. In a previous study, we developed an NLC core consisting of a solid lipid (CrodamolTM CP), a lipophilic liquid with medium polarity (SRTM Lauryl lactate), and a hydrophilic excipient (SRTM DMI) that allowed the solubilization of 'brick dust' types of drugs, including butamben. In this study, starting from the NLC core formulation previously developed we carried out an optimization of the surfactant system and evaluated their performance in aqueous medium. Three different surfactants (CrodasolTM HS HP, SynperonicTM PE/F68, and CroduretTM 40) were studied and, for each of them, a 23 factorial design was stablished, with total lipids, % surfactant, and sonication time (min) as the input variables and particle size (nm), polydispersity index (PDI), and zeta potential (mV) as the response variables. Stable NLCs were obtained using CrodasolTM HS HP and SynperonicTM PE/F68 as surfactants. Through a comparison between NLCs developed with and without SRTM DMI, it was observed that besides helping the solubilization of butamben in the NLC core, this excipient helped in stabilizing the system and decreasing particle size. NLCs containing CrodasolTM HS HP and SynperonicTM PE/F68 presented particle size values in the nanometric scale, PDI values lower than 0.3, and zeta potentials above |10|mV. Concerning NLCs' stability, SBTB-NLC with SynperonicTM PE/F68 and butamben demonstrated stability over a 3-month period in aqueous medium. The remaining NLCs showed phase separation or precipitation during the 3-month analysis. Nevertheless, these formulations could be freeze-dried after preparation, which would avoid precipitation in an aqueous medium.

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Laccase is an exothermic enzyme with copper in its structure and has an important role in biodegradation by providing oxidation of phenolic compounds and aromatic amines and decomposing lignin. The aim of this study is to reach maximum laccase enzyme activity with minimum cost and energy through optimization studies of Proteusmirabilis isolated from treatment sludge of a textile factory. In order to increase the laccase enzyme activities of the isolates, medium and culture conditions were optimized with the study of carbon (Glucose, Fructose, Sodium Acetate, Carboxymethylcellulose, Xylose) and nitrogen sources (Potassium nitrate, Yeast Extract, Peptone From Soybean, Bacteriological Peptone), incubation time, pH, temperature and Copper(II) sulfate concentration then according to the results obtained. Response Surface Method (RSM) was performed on six different variables with three level. According to the data obtained from the RSM, the maximum laccase enzyme activity is reached at pH 7.77, temperature 30.03oC, 0.5 g/L CuSO4, 0.5 g/L fructose and 0.082 g/L yeast extract conditions. After all, the laccase activity increased 2.7 times. As a result, laccase activity of P. mirabilis can be increased by optimization studies. The information obtained as a result of the literature studies is that the laccase enzymes produced in laboratory and industrial scale are costly and their amounts are low. This study is important in terms of obtaining more laccase activity from P.mirabilis with less cost and energy.

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The objective of this study was to develop a versatile lipid core for the 'brick-dust type of drugs' (poorly water-soluble and poorly lipid-soluble drugs). In the first step, excipients of different polarities were classified according to their behavior in aqueous solutions. Subsequently, binary mixtures were prepared with cetyl palmitate (Crodamol™ CP pharma, Campinas, São Paulo, Brazil) as the solid lipid, and its miscibility with other excipients was evaluated using Raman mapping and classical least squares (CLS). Based on the results, the excipients Crodamol™ CP pharma (hydrophobic), Super Refined™ DMI (dimethyl isosorbide; hydrophilic, Mill Hall, PA, USA), and Super Refined™ Lauryl Lactate (lauryl lactate, medium polarity, Mill Hall, PA, USA) were chosen to compose the lipid core. The ideal proportion of these excipients was determined using a mixture design and the standard deviation (STD) of image histograms as the response variables. After statistical evaluation of the DoE results, the final composition was determined, and drugs with different logP (0 to 10) and physicochemical characteristics were evaluated in the optimized mixture. The drugs butamben (Sigma-Aldrich Co., Spruce Street, St. Louis, MO, USA), tacrolimus (NutriFarm, São Paulo, Brazil), atorvastatin calcium, and resveratrol (Botica da Terra, Campinas, Brazil) presented a homogeneous distribution in the optimized lipid core, indicating that this is a promising system to be used in nanostructured lipid carrier (NLC) formulations of such types of drugs.

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Aniba canelilla (Kunth) Mez is an aromatic tree from Amazon region whose essential oil presents 1-nitro-2-phenylethane (NP) and methyleugenol (ME) as major compounds. Several properties are attributed to Aniba canelilla essential oil (ACEO), such as antifungal. Onychomycoses are fungal nail infections that require novel therapeutic alternatives, especially topical ones. However, to ensure the success of topical therapy, the active compound should be able to penetrate/permeate the nail plate, which is challenging due to the highly keratinized composition of this structure. Thus, the aims of this article were to develop, validate and apply a high-performance liquid chromatography method (HPLC-UV) to quantify NP and ME in porcine hoof extract (PHE) and receptor fluid (RF) during in vitro permeation/retention studies in nail model, for which porcine hoof membranes were used. For method development, two Designs of Experiment (DoE) were adopted: 23 Full Factorial and Box-Behnken. Retention times of 5.65 and 7.49 min were achieved for NP and ME, respectively. The method was full validated for NP and ME quantification in receptor fluid, in accordance with the recommended parameters by ICH Q2(R1) Guideline. In addition, the method was full validated for NP and ME quantification in porcine hoof extract, considering the parameters and criteria of ICH M10 Guideline. In vitro permeation/retention studies were carried out in nail model, and promising results were obtained. NP reached the receptor fluid in the order of 441.1 ± 92.1 µg/cm2 at 72 h. The amount of NP and ME retained into porcine hoof membrane was 1272.6 ± 225.7 µg/cm2 and 84.7 ± 20.4 µg/cm2, respectively, at 72 h. Our findings open perspective to develop topical formulations containing ACEO as active compound aiming the management of onychomycosis.

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Introduction: Cell membrane-covered biomimetic nanosystems have allowed the development of homologous nanostructures to bestow nanoparticles with enhanced biointerfacing capabilities. The stability of these structures, however, still represents a challenge for the scientific community. This study is aimed at developing and optimizing cell derived membrane-coated nanostructures upon applying design of experiments (DoE) to improve the therapeutic index by homotypic targeting in cancer cells. Methods: Important physicochemical features of the extracted cell membrane from tumoral cells were assessed by mass spectrometry-based proteomics. PLGA-based nanoparticles encapsulating temozolomide (TMZ NPs) were successfully developed. The coating technology applying the isolated U251 cell membrane (MB) was optimized using a fractional two-level three-factor factorial design. All the formulation runs were systematically characterized regarding their diameter, polydispersity index (PDI), and zeta potential (ZP). Experimental conditions generated by DoE were also subjected to morphological studies using negative-staining transmission electron microscopy (TEM). Its short-time stability was also assessed. MicroRaman and Fourier-Transform Infrared (FTIR) spectroscopies and Confocal microscopy were used as characterization techniques for evaluating the NP-MB nanostructures. Internalization studies were carried out to evaluate the homotypic targeting ability. Results and Discussion: The results have shown that nearly 80% of plasma membrane proteins were retained in the cell membrane vesicles after the isolation process, including key proteins to the homotypic binding. DoE analysis considering acquired TEM images reveals that condition run five should be the best-optimized procedure to produce the biomimetic cell-derived membrane-coated nanostructure (NP-MB). Storage stability for at least two weeks of the biomimetic system is expected once the original characteristics of diameter, PDI, and ZP, were maintained. Raman, FTIR, and confocal characterization results have shown the successful encapsulation of TMZ drug and provided evidence of the effective coating applying the MB. Cell internalization studies corroborate the proteomic data indicating that the optimized NP-MB achieved specific targeting of homotypic tumor cells. The structure should retain the complex biological functions of U251 natural cell membranes while exhibiting physicochemical properties suitable for effective homotypic recognition. Conclusion: Together, these findings provide coverage and a deeper understanding regarding the dynamics around extracted cell membrane and polymeric nanostructures interactions and an in-depth insight into the cell membrane coating technology and the development of optimized biomimetic and bioinspired nanostructured systems.

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Chagas disease is a neglected tropical disease affecting the American continent and also some regions of Europe. Benznidazole, approved by FDA, is a drug of choice but its poor aqueous solubility may lead to a low bioavailability and efficacy. Therefore, the aim of this study was to formulate nanoparticles of benznidazole for improving its solubility, dissolution and permeability. A Plackett-Burman design was applied to identify the effect of 5 factors over 4 responses. Then, a Central Composite design was applied to estimate the values of the most important factors leading to the best compromise between highest nanoprecipitation efficiency, drug solubility and lower particle size. The optimized nanoparticles were evaluated for in vitro drug release in biorelevant media, stability studies and transmission electron microscopy. Biocompatibility and permeability of nanoparticles were evaluated on the Caco-2 cell line. The findings of the optimization process indicated that concentration of drug and stabilizer influenced significantly the particle size while concentration of stabilizer and organic/water phase volume ratio mainly influenced the drug solubility. Stability studies suggested that benznidazole nanoparticles were stable after 12 months at different temperatures. Minimal interactions of those nanoparticles and mucin glycoproteins suggested favorable properties to address the intestinal mucus barrier. Cell viability studies confirmed the safety profile of the optimized formulation and showed an increased permeation through the Caco-2 cells. Thus, this study confirmed the suitability of the design of experiment and optimization approach to elucidate critical parameters influencing the quality of benznidazole nanoparticles, which could lead to a more efficient management of Chagas disease by oral route.

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The effects of acid and organo-functionalizations on the surface of Brazilian palygorskite clay was investigated, evaluating its potential in the adsorptive capacity of the drug sodium diclofenac present in wastewaters. The modifications on the clay structure were investigated by X-ray diffraction, X-ray fluorescence, thermogravimetric, differential thermal analysis, Fourier transform infrared spectroscopy, surface area by N2 adsorption (77.5 K) and Zeta potential. The experimental design was carried out to find the best conditions for the adsorption tests, in which concentration, mass and pH were significant. In the kinetic study, the pseudo-second-order model better described the adsorption process for acid and organo-functionalized samples. Such results indicate that the adsorption behavior probably occurs due to the phenomenon of chemisorption. Regarding the adsorption isotherms, the Langmuir model was the one that best adjusted both the experimental data of acid and the organo-functionalized samples, whose maximum adsorption capacity were 179.88 and 253.34 mg/g, respectively. This model also indicates that the sodium diclofenac is adsorbed to monolayers homogeneously through chemisorption. In general, the studied clays proved to be suitable adsorbents for the removal of sodium diclofenac.

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Today, a growing number of computational aids and simulations are shaping model-informed drug development. Artificial intelligence, a family of self-learning algorithms, is only the latest emerging trend applied by academic researchers and the pharmaceutical industry. Nanomedicine successfully conquered several niche markets and offers a wide variety of innovative drug delivery strategies. Still, only a small number of patients benefit from these advanced treatments, and the number of data sources is very limited. As a consequence, "big data" approaches are not always feasible and smart combinations of human and artificial intelligence define the research landscape. These methodologies will potentially transform the future of nanomedicine and define new challenges and limitations of machine learning in their development. In our review, we present an overview of modeling and artificial intelligence applications in the development and manufacture of nanomedicines. Also, we elucidate the role of each method as a facilitator of breakthroughs and highlight important limitations.

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Abstract The purpose of this study is to optimize the composition of extragranular excipients (EGE) and mixing time of granules with EGE of paracetamol tablet formulation using Design of Experiments (DoE) approach. The effect of the composition of EGE and the mixing time of granules with EGE on granule and tableting properties of paracetamol tablet formulation was investigated using a combined model of mixture and process factors (Design-Expert 12). A total of 18 tablet formulations were manufactured by wet granulation using varying compositions of EGE and varying mixing time. Granule and tablet properties of each formulation were evaluated as response variables for the design, data generated were fitted into models and analysed to generate a design space that was used for optimization studies. The proposed EGE composition as predicted by the design was confirmed and validated after preparation and evaluation of the granule and tablet properties. The optimized composition for the EGE that yielded granules and tablets of desirable characteristics was found to be maize starch (5 %), talc (4.9 %) and magnesium stearate (0.1 %) with a mixing time of 2 min. The tablets produced with the optimized composition had better mechanical strength and disintegration time than the formulation prepared using an existing formula of maize starch (7.8 %), talc (2 %) and magnesium stearate (0.2 %) that were obtained using the One Variable at a Time (OVAT) approach. This study confirmed the relevance of quality by design in development of pharmaceutical formulations.

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Abstract Design of experiment (DoE) is a useful time and cost-effective tool for analyzing the effect of independent variables on the formulation characteristics. The aim of this study is to evaluate the effect of the process variables on the characteristics involved in the preparation of Diclofenac Sodium (DC) loaded ethylcellulose (EC) nanoparticles (NP) using Central Composite Design (CCD). NP were prepared by W/O/W emulsion solvent evaporation method. Three factors were investigated (DC/EC mass ratio, PVA concentration, homogenization speed) in order to optimize the entrapment efficiency (EE) and the particle size of NP. The optimal formulation was characterized by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and in vitro release. Optimized formulation showed an EE of 49.09 % and an average particle size of 226.83 nm with a polydispersity index of 0.271. No drug-polymer interaction was observed in FTIR and DSC analysis. SEM images showed that the particles are spherical and uniform. The in vitro release study showed a sustained release nature, 53.98 % of the encapsulated drug has been released over 24hours period. This study demonstrated that statistical experimental design methodology can optimize the formulation and the process variables to achieve favorable responses.

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Forced degradation tests are studies used to assess the stability of active pharmaceutical ingredients (APIs) and their formulations. These tests are performed submitting the API under extreme conditions in order to know the main degradation products in a short period of time. The results of these studies are used to assess the degradation susceptibility of APIs and to validate chromatographic analytical methods. However, most of degradation studies are performed using one-factor-at-the-time (OFAT) which does not consider the interactions between degradation variables. This work proposes the use of Design of Experiment (DoE) approach in forced degradation of albendazole (ABZ). It was used a central composite design (CCD) to evaluate the forced degradation in a multivariate way. Experiments were performed taking into account the variables pH, temperature, oxidizing agent (H2O2) and UV radiation. It was verified the influence of the variables and their interactions on the ABZ degradation. The ABZ oxidation showed to be the main degradation route for ABZ, which is strongly influenced by the temperature. The hydrolysis was relevant at alkaline medium and high temperature. LC-IT-MSn was used to identify the degradation products. It was found three known degradation products (albendazole-2-amino, albendazole sulfoxide and albendazole sulfone) and a new derivate of albendazole molecule (albendazole sulfoxide with a chlorine). This last one was isolated and characterized by UPLC-QToF-MS and NMR analyses.

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The present study introduces the analysis of single-lap co-cured joints of thermoplastic self-reinforced composites made with reprocessed low-density polyethylene (LDPE) and reinforced by ultra-high-molecular-weight polyethylene (UHMWPE) fibers, along with a micromechanical analysis of its constituents. A set of optimal processing conditions for manufacturing these joints by hot-press is proposed through a design of experiment using the response surface method to maximize their in-plane shear strength by carrying tensile tests on co-cured tapes. Optimal processing conditions were found at 1 bar, 115 °C, and 300 s, yielding joints with 6.88 MPa of shear strength. The shear failure is generally preceded by multiple debonding-induced longitudinal cracks both inside and outside the joint due to accumulated transversal stress. This composite demonstrated to be an interesting structural material to be more widely applied in industry, possessing extremely elevated specific mechanical properties, progressive damage of co-cured joints (thus avoiding unannounced catastrophic failures) and ultimate recyclability.

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Navicula incerta is a marine microalga distributed in Baja California, México, commonly used in aquaculture nutrition, and has been extended to human food, biomedical, and pharmaceutical industries due to its high biological activity. Therefore, the study aimed to optimize culture conditions to produce antioxidant pigments. A central composite experimental design and response surface methodology (RSM) was employed to analyze the best culture conditions. The medium (nitrogen-deficient concentrations), salinity (PSU = Practical Salinity Unity [g/kg]), age of culture (days), and solvent extraction (ethanol, methanol, and acetone) were the factors used for the experiment. Chlorophyll a (Chl a) and total carotenoids (T-Car), determined spectroscopically, were used as the response variables. The antioxidant capacity was evaluated by DPPH• and ABTS•+ radical inhibition, FRAP, and anti-hemolytic activity. According to the overlay plots, the optimum growth conditions for Chl a and T-Car production were the following conditions: medium = 0.44 mol·L-1 of NaNO3, salinity = 40 PSU, age of culture: 3.5 days, and solvent = methanol. The pigment extracts obtained in these optimized conditions had high antioxidant activity in ABTS•+ (86.2-92.1% of inhibition) and anti-hemolytic activity (81.8-96.7% of hemolysis inhibition). Low inhibition (33-35%) was observed in DPPH•. The highest value of FRAP (766.03 ± 16.62 µmol TE/g) was observed in the acetonic extract. The results demonstrated that RSM could obtain an extract with high antioxidant capacity with potential applications in the biomedical and pharmaceutical industry, which encourages the use of natural resources for chemoprevention of chronic-degenerative pathologies.

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Atropine is an antimuscarinic alkaloid identified in Atropa belladonna. In pharmacopeias, percolation is standardized as an extraction method for A. belladonna leaves, along with liquid-liquid extraction as a cleanup procedure and titration as an analytical method for assaying the atropine in the leaves. In this study, a faster, solvent-saving, and more reliable method for quality control of A. belladonna samples was developed. Ultrasound-assisted extraction was proposed and optimized by fractional factorial design followed by Box-Behnken design. For modeling atropine content, the following optimal conditions were established: particle size, 180 µm; percentage methanol in water, 50%; volume of solvent, 15 ml; time of extraction, 60 min; and number of extractions, two. This led to a significant improvement in atropine extraction (P < 0.001). For cleanup, solid-phase extraction was used as an alternative to liquid-liquid extraction, giving similar results, with higher reproducibility. Finally, for the atropine assay, a UPLC method was validated as a substitute for the classic titration method. Taken together, the development of an ultrasound-assisted extraction-solid-phase extraction-UPLC approach allowed the determination of atropine content in A. belladonna leaves in a time- and solvent-saving manner, with high reliability.

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This work aims to improve the functionality of Rosmarinus officinalis L. (rosemary) polyphenols by encapsulation in an optimized proliposome formulation. A 23 Box-Wilson central composite design (CCD) was employed to determine lone and interaction effects of composition variables on moisture content (Xp); water activity (Aw); concentration and retention of rosemary polyphenols-rosmarinic acid (ROA), carnosol (CAR), and carnosic acid (CNA); and recovery of spray-dried proliposomes (SDP). Processing conditions which generate proliposomes with optimum physicochemical properties were determined by multi-response analysis (desirability approach). Antioxidant and antifungal activities were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH•) sequestering and minimum inhibitory concentration (MIC)/minimum fungicidal concentration (MFC) assays, respectively. SDP exhibited high polyphenol retention, ranging from 62.0 to 100.0% w/w, showing dependence on composition variables and polyphenol lipophilicity. SDP recovery ranged from 20.1 to 45.8%, with Xp and Aw of 1.7 ± 0.14-2.5 ± 0.23% w/w and 0.30 ± 0.004-0.47 ± 0.003, respectively, evidencing product with good chemical and microbiological stability. Optimum liposomal composition was determined, namely, lipid concentration (4.26% w/w), lyophilized extract (LE) concentration (4.48% w/w), and drying aid:(lipid+extract) ratio (7.55% w/w) on wet basis. Relative errors between experimental and predicted values for SDP properties showed concurrence for all responses except CAR retention, being 22% lower. SDP showed high antioxidant activity with IC50 of 9.2 ± 0.2 µg/mL, superior to results obtained for LE (10.8 µg/mL) and butylated hydroxytoluene (BHT), a synthetic antioxidant (12.5 µg/mL). MIC and MFC against Candida albicans (ATCC1023) were 312.5 µg/mL and 1250 µg/mL, respectively, a moderate antimicrobial activity for phytochemical-based products. SDP is shown as a veritable tool to encapsulate hydrophilic and lipophilic rosemary polyphenols generating a product with optimal physicochemical and biological properties.

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Present study was aimed to prepare and characterize fluconazole loaded nanostructured lipid carriers (FLZ-NLCs) for the treatment of fungal infections. Fungal infections are tremendously widespread and are the often faced dermatological condition worldwide. FLZ-NLCs was prepared by ultrasonication emulsion technique using stearic acid (SA) as solid lipid, castor oil as liquid lipid and tween 20 as a surfactant. The mean diameter of optimized FLZ-NLCs were found to be 359.15 ± 9.83 nm. The drug content and entrapment efficiency of NLCs was found to be 102.97 ± 7.45% and 87 ± 0.59%, respectively. In vitro drug release studies of FLZ-NLCs showed 37.34 ± 2.08% drug release over a period of 72 h. The above studies confirmed the prepared FLZ-NLCs may be useful for the treatment of fungal infections.

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In this article, data from a 3.5kW mini split air conditioning is presented. A screening 23 design experiment was performed to evaluate the effects of indoor air temperature, absolute humidity and evaporator fan speed in the performance of the air conditioning. This dataset also includes noise factors as outdoor air temperature, fans energy consumption and response as indoor air exit conditions.

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Fenticonazole is an antifungal drug widely used in a cream formulation including as a generic medicine. Stability studies of fenticonazole in a cream formulation are very scarce. In this research, we intent to contribute to generic medicines quality control and provide reliable data seeking for insertion of fenticonazole monograph in official compendia. Therefore, in this work it was studied the behavior of fenticonazole under several conditions and developed a stability-indicating LC method to separate the degradation products and quantify the drug in presence of them, using the Design of Experiments (DoE) as tool to achieve robust and easy transferable method. Fenticonazole stability was evaluated under aqueous, alkaline (0.1 M NaOH), acidic (0.1 M HCL) and oxidative (3% v/v, H2O2) at ambient temperature and heating at 90°C, over 6 hours. The drug shows to be unstable under all stressed test conditions. It was completely degraded under acid medium with arising of degradation products. The robust and stability indicating LC method was validated. It is able to reveal the fenticonazole instability and to separate its degradation product with accuracy and precision (CV ˂ 2%) and without any placebo interferences.(AU)

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Polyurethanes are materials with a strong structure-property relationship. The goal of this research was to study the effect of a polyol blend composition of polyurethanes on its properties using a mixture design and setting mathematic models for each property. Water absorption, hydrolytic degradation, contact angle, tensile strength hardness and modulus were studied. Additionally, thermal stability was studied by thermogravimetric analysis. Area under the curve was used to evaluate the effect of polyol blend composition on thermal stability and kinetics of water absorption and hydrolytic degradation. Least squares were used to calculate the regression coefficients. Models for the properties were significant, and lack of fit was not (p < 0.05). Fit statistics suggest both good fitting and prediction. Water absorption, hydrolytic degradation and contact angle were mediated by the hydrophilic nature of the polyols. Tensile strength, modulus and hardness could be regulated by the PE content and the characteristics of polyols. Regression of DTG curves from thermal analysis showed improvement of thermal stability with the increase of PCL and PE. An ANOVA test of the model terms demonstrated that three component influences on bulk properties like water absorption, hydrolytic degradation, hardness, tensile strength and modulus. The PEG*PCL interaction influences on the contact angle, which is a surface property. Mixture design application allowed for an understanding of the structure-property relationship through mathematic models.

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The aim of the work was to develop rhein loaded polymeric nanoparticles (R-PNPs). Nanoparticles were prepared by three methods, solvent emulsion-evaporation, double emulsion, and nanoprecipitation, by means of experimental design. Additionally, the effects of the best formulation on in vitro cytotoxicity and inflammation were evaluated. The solvent emulsion-evaporation method presented the highest encapsulation efficiency of the three techniques (38.41%), as well as had a mean diameter of 189.33 nm and a polydispersity index of less than 0.1. Despite efforts to optimize the encapsulation of rhein, the drug release from nanoparticles was close to 50% during the first 5 min, followed by a continuous release within 60 min. It was observed that macrophages exposed to the highest concentration of R-PNPs showed cell viability about 80% and at the lowest nanoparticle concentrations was closed to 100%. IL-1ß in cell culture supernatants was decreased in the presence of R-PNPs and TNFα concentrations were lower than the sensitivity of the assay. ROS production was only inhibited with R-PNPs at concentrations of 2.5 and 5 µM. In conclusion, the solvent emulsion-evaporation was the best method evaluated to obtain nanoparticles with the desired specifications. It was possible to assess R-PNPs with low cytotoxicity and anti-inflammatory properties showed by the inhibition of IL-1ß production and a low decrease in ROS production.

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