Comparison of the Therapeutic Effects of Adipose- and Bone Marrow-Derived Mesenchymal Stem Cells on Renal Fibrosis.

Mesenchymal stem cells (MSCs) have attracted a great deal of interest as a therapeutic tool for renal fibrosis. Although both adipose-derived and bone marrow-derived MSCs (ADSCs and BMSCs, respectively) suppress renal fibrosis, which of these two has a stronger therapeutic effect remains unclear. This study aimed to compare the antifibrotic effects of ADSCs and BMSCs extracted from adipose tissue and bone marrow derived from the same rats. When cultured in serum-containing medium, ADSCs had a more potent inhibitory effect than BMSCs on renal fibrosis induced by ischemia-reperfusion injury in rats. ADSCs and BMSCs cultured in serum-free medium were equally effective in suppressing renal fibrosis. Mice infused with ADSCs (serum-containing or serum-free cultivation) had a higher death rate from pulmonary embolism than those infused with BMSCs. In vitro, mRNA levels of tissue factor, tumor necrosis factor-α-induced protein 6 and prostaglandin E synthase were higher in ADSCs than in BMSCs, while that of vascular endothelial growth factor was higher in BMSCs than in ADSCs. Although ADSCs had a stronger antifibrotic effect, these findings support the consideration of thromboembolism risk in clinical applications. Our results emphasize the importance of deciding between ADSCs and BMSCs based upon the target disease and culture method.

Effects of neutron radiation generated in deep space-like environments on food resources.

The impact of deep space cosmic rays on food resources is as important as the risks of cosmic rays to the human body. This study demonstrates the potential for neutrons as secondary radiation in deep space spacecraft to cause meat activation and oxidative modification of proteins and lipids. We conducted a series of experiments such as the neutron irradiation experiment, the radioactivation analysis and the biochemical analysis. Neutrons with energies from 1 to 5 MeV with doses from 0.01 Gy to 4 Gy were irradiated by the RIKEN accelerated-driven neutron source (RANS). Radioactive nuclei, 24Na, 42K, and 38Cl, were detected in the neutron-irradiated meat. The modification products of the proteins by oxidative nitration, 6-nitrotryptophan (6NO2Trp), and by a lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE), were detected in several proteins with neutron dose dependent. The proteome analysis showed that many oxidative modifications were detected in actin and myosin which are major proteins of myofibrils. This study is of crucial importance not only as risk factors for human space exploration, but also as fundamental effects of radiation on the components of the human body.

Thermal energy and tableting effects in benznidazole product: the impacts of industrial processing.

OBJECTIVE: The investigation of benznidazole (BZN), excipients, and tablets aims to evaluate their thermal energy and tableting effects. They aim to understand better the molecular and pharmaceutical processing techniques of the formulation. SIGNIFICANCE: The Product Quality Review, part of Good Manufacturing Practices, is essential to highlight trends and identify product and process improvements. METHODS: A set of technique approaches, infrared spectroscopy, X-ray diffraction, and thermal analysis with isoconversional kinetic study, were applied in the protocol. RESULTS: X-ray experiments suggest talc and α-lactose monohydrate dehydration and conversion of ß-lactose to stable α-lactose upon tableting. The signal crystallization at 167 °C in the DSC curve confirmed this observation. A calorimetric study showed a decrease in the thermal stability of BZN tablets. Therefore, the temperature is a critical process parameter. The specific heat capacity (Cp) of BZN, measured by DSC, was 10.04 J/g at 25 °C and 9.06 J/g at 160 °C. Thermal decomposition required 78 kJ mol-1. Compared with the tablet (about 200 kJ mol-1), the necessary energy is two-fold lower, as observed in the kinetic study by non-isothermal TG experiment at 5; 7.5; 10; and 15 °C min-1. CONCLUSIONS: These results indicate the necessity of considering the thermal energy and tableting effects of BZN manufacturing, which contributes significantly to the molecular mechanistic understanding of this drug delivery system.

Solid-state properties of pink clay from Jequitinhonha Valley in Brazil for pre-formulation study

Abstract Clay minerals are still widely used in pharmaceutical products for human health and cosmetic purposes. Pre-formulation studies were conducted to identify solid-state properties of pink clay, a sample from Diamantina, Brazil. Among the solid properties to be analyzed, we have selected type identification, iron phases, crystallinity, powder flow characteristics, thermal behavior, and non-isothermal phase transition kinetics. The pink clay is composed of (1:1) clay type and kaolinite as the main component. The Mössbauer spectrum of pink clay shows Fe3+(α-Fe2O3) Clay minerals are still widely used in pharmaceutical products for human health and cosmetic purposes. Pre-formulation studies were conducted to identify solid-state properties of pink clay, a sample from Diamantina, Brazil. Among the solid properties to be analyzed, we have selected type identification, iron phases, crystallinity, powder flow characteristics, thermal behavior, and non-isothermal phase transition kinetics. The pink clay is composed of (1:1) clay type and kaolinite as the main component. The Mössbauer spectrum of pink clay shows Fe3+(α-Fe2O3) hematite, Fe2+, and Fe3+ with large Δ/2ξq of about 2.80 and 2.69 mm.s-1 respectively, related to iron silicates, most likely pyroxene, and a superparamagnetic Fe3+. Pink clay exhibits poor flow properties. The thermal behavior indicates a phase-transition between 400 - 600 ºC associated with the dehydroxylation of the pink clay system requiring ~300 kJ mol-1, being constant until the process reaches a conversion of ~50% when the energy is enhanced to ~530 kJ mol-1, concluding the whole dehydroxylation process (α=80%). Solid-state properties and characteristics found for the pink clay must be considered for the proper design of formulations. This type of clay shows unique pharmaceutical properties that can be favorably exploited by the cosmetic industry

Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain

Abstract Chagas disease is a neglected parasitic disease caused by Trypanosoma cruzi, whose treatment has remained unsatisfactory for over 50 years, given that it is limited to two drugs. Benznidazole (BZN) is an efficient antichagasic drug used as the first choice, although its poor water-solubility, irregular oral absorption, low efficacy in the chronic phase, and various associated adverse effects are limiting factors for treatment. Incorporating drugs with such characteristics into nanostructured lipid carriers (NLC) is a promising alternative to overcome these limiting obstacles, enhancing drug efficacy and bioavailability while reducing toxicity. Therefore, this study proposed NLC-BZN formulations in different compositions prepared by hot-melt homogenization followed by ultrasound, and the optimized formulation was characterized by FTIR, DRX, DSC, and thermogravimetry. Biological activities included in vitro membrane toxicity (red blood cells), fibroblast cell cytotoxicity, and trypanocidal activity against epimastigotes of the Colombian strain of T. cruzi. The optimized NLC-BZN had a small size (110 nm), negative zeta potential (-18.0 mV), and high encapsulation (1.64% of drug loading), as shown by infrared spectroscopy, X-ray diffraction, and thermal analysis. The NLC-BZN also promoted lower in vitro membrane toxicity (<3% hemolysis), and 50% cytotoxic concentration (CC50) for NLC-BZN in L929 fibroblast cells (110.7 µg/mL) was twice the value as the free BZN (51.3 µg/mL). Our findings showed that the NLC-BZN had higher trypanocidal activity than free BZN against the epimastigotes of the resistant Colombian strain, and this novel NLC-BZN formulation proved to be a promising tool in treating Chagas disease and considered suitable for oral and parenteral administration

Effect of polyvinyl alcohol and carboxymethylcellulose on the technological properties of fish gelatin films.

The objective of this work was to develop biodegradable films by mixing gelatin/carboxymethylcellulose (FG/CMC) and gelatin/polyvinyl alcohol (FG/PVOH) and to evaluate the effect of adding these polymers on the properties of fish gelatin films. The films FG/CMC and FG/PVOH were produced in the proportions 90/10, 80/20 and 70/30 and characterized their physical, chemical and functional properties. The addition of CMC and PVOH improved the mechanical strength, barrier property and water solubility of gelatin films. FG/CMC films showed greater tensile strength and greater solubility than FG/PVOH. The maximum concentration of CMC promoted the highest mechanical resistance, while the highest PVOH content produced the film with the lowest solubility. The proposed mixing systems proved to be adequate to improve the properties of fish gelatin films, with potential for application in the packaging sector.

Encapsulation of safflower oil in nanostructured lipid carriers for food application.

Safflower oil (SO) is mainly rich in linoleic acid (ω-6), oleic acid (ω-9), and other bioactives with potential antioxidant, antidiabetic, thermogenic, anti-inflammatory, cardioprotective and anticancer activities. The reduced aqueous solubility and high susceptibility to oxidative degradation are undesirable for food applications and can be overcome by incorporation in lipid nanoparticles. Thus, the main goal was to develop and characterize SO-loaded nanostructured lipid carriers (NLC-SO) and to evaluate their potential for protection of the antioxidant activity of the bioactive. NLC-SO showed average size of 222 ± 2.0 nm, zeta potential of  43 ± 3.5 mV and the encapsulation efficiency was 49.0 ± 2.8%, combined with high thermal compatibility (up to 228 °C) and physical stability for up to 60 days in aqueous dispersion. Besides, the NLC-SO showed threefold reduction in the DPPH radical scavenge activity after encapsulation, indicating protection of the antioxidant components of the SO and preservation of the bioactives. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05078-5.

Development and characterization of PLGA-Bupivacaine and PLGA-S75: R25 Bupivacaine (Novabupi®) biodegradable implants for postoperative pain

Abstract In the hospital environment, postoperative pain is a common occurrence that impairs patient recovery and rehabilitation and lengthens hospitalization time. Racemic bupivacaine hydrochloride (CBV) and Novabupi® (NBV) (S (-) 75% R (+) 25% bupivacaine hydrochloride) are two examples of local anesthetics used in pain management, the latter being an alternative with less deleterious effects. In the present study, biodegradable implants were developed using Poly(L-lactide-co-glycolide) through a hot molding technique, evaluating their physicochemical properties and their in vitro drug release. Different proportions of drugs and polymer were tested, and the proportion of 25%:75% was the most stable for molding the implants. Thermal and spectrometric analyses were performed, and they revealed no unwanted chemical interactions between drugs and polymer. They also confirmed that heating and freeze-drying used for manufacturing did not interfere with stability. The in vitro release results revealed drugs sustained release, reaching 64% for NBV-PLGA and 52% for CBV-PLGA up to 30 days. The drug release mechanism was confirmed by microscopy, which involved pores formation and polymeric erosion, visualized in the first 72 h of the in vitro release test. These findings suggest that the developed implants are interesting alternatives to control postoperative pain efficiently.

Thermal Stability Kinetics and Shelf Life Estimation of the Redox-Active Therapeutic and Mimic of Superoxide Dismutase Enzyme, Mn(III) meso-Tetrakis(N-ethylpyridinium-2-yl)porphyrin Chloride (MnTE-2-PyPCl5, BMX-010).

Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin chloride (MnTE-2-PyPCl5, BMX-010, and AEOL10113) is among the most studied superoxide dismutase (SOD) mimics and redox-active therapeutics, being currently tested as a drug candidate in a phase II clinical trial on atopic dermatitis and itch. The thermal stability of active pharmaceutical ingredients (API) is useful for estimating the expiration date and shelf life of pharmaceutical products under various storage and handling conditions. The thermal decomposition and kinetic parameters of MnTE-2-PyPCl5 were determined by thermogravimetry (TG) under nonisothermal and isothermal conditions. The first thermal degradation pathway affecting Mn-porphyrin structural integrity and, thus, activity and bioavailability was associated with loss of ethyl chloride via N-dealkylation reaction. The thermal stability kinetics of the N-dealkylation process leading to MnTE-2-PyPCl5 decomposition was investigated by using isoconversional models and artificial neural network. The new multilayer perceptron (MLP) artificial neural network approach allowed the simultaneous study of ten solid-state kinetic models and showed that MnTE-2-PyPCl5 degradation is better explained by a combination of various mechanisms, with major contributions from the contraction models R1 and R2. The calculated activation energy values from isothermal and nonisothermal data were about 90 kJ mol-1 on average and agreed with one another. According to the R1 modelling of the isothermal decomposition data, the estimated shelf life value for 10% decomposition (t 90%) of MnTE-2-PyPCl5 at 25°C was approximately 17 years, which is consistent with the high solid-state stability of the compound. These results represent the first study on the solid-state decomposition kinetics of Mn(III) 2-N-alkylpyridylporphyrins, contributing to the development of this class of redox-active therapeutics and SOD mimics and providing supporting data to protocols on purification, handling, storage, formulation, expiration date, and general use of these compounds.

Lower Geriatric Nutritional Risk Index (GNRI) Is Associated with Higher Risk of Fractures in Patients Undergoing Hemodialysis.

BACKGROUND: Although malnutrition and bone fracture are both major complications in patients undergoing hemodialysis, their association has not been clarified. The aim of our study was to clarify the association between the geriatric nutritional risk index (GNRI), an indicator of nutritional status, and the incidence of bone fractures in patients undergoing hemodialysis. METHODS: We included 1342 registered patients undergoing hemodialysis and performed a post hoc analysis. We divided patients into the high GNRI group (≥92), considered to have a low risk of malnutrition, and the low GNRI group (<92), considered to have a high risk of malnutrition. Fracture-free survival in the low and high GNRI groups was evaluated by the Kaplan-Meier method. Cox proportional hazards models were used to identify the risk factors for fractures requiring hospitalization. All results were stratified by sex. RESULTS: New bone fractures developed in 108 (8.0%) patients in 5 years of follow-up. Bone fractures occurred more frequently in the low GNRI group compared with the high GNRI group (HR: 3.51, 95% CI: 1.91-6.42, p < 0.01 in males; HR: 2.47, 95% CI: 1.52-4.03, p < 0.01 in females). A low GNRI was significantly associated with an increased incidence of bone fractures, even after adjustment for covariates. However, the serum levels of calcium, phosphate, parathyroid hormone, and alkaline phosphatase were not associated with the incidence of bone fractures. CONCLUSIONS: A low GNRI is an independent risk factor for bone fractures in patients undergoing hemodialysis. Early intervention for the low GNRI group may be important in preventing the occurrence of fractures.

Effect of the incorporation of lignin microparticles on the properties of the thermoplastic starch/pectin blend obtained by extrusion.

The present study aimed to produce thermoplastic starch films with different concentrations of thermoplastic pectin and the addition of 4% lignin microparticles as a reinforcing and active agent. The pectin improved the modulus of elasticity, and decreased the elongation at break. In addition, it improved the UV light protection to 100% at 320 nm and 95.9% at 400 nm. The incorporation of lignin microparticles improved the thermal stability of the blends made with 25% and 50% thermoplastic pectin when compared to the pectin-free blends. The blend with 25% thermoplastic pectin led to an increase of 75.8% and 34% in elongation at break and deformation of the films, respectively. This blend also improved the UV light protection to 100% due to its dark brown color. Regarding the permeability properties, the films with 25% and 50% thermoplastic pectin showed lower oxygen permeability (48% and 65%) and an increase in the antioxidant activities from 2.7% to 71.08% and 4.1% to 79.28%, respectively. Thus, the polymer blend with 25% thermoplastic pectin with the incorporation of lignin microparticles proved to be a good alternative for use in foods sensitive to the effects of oxygen and UV light.

Low-Vacuum Scanning Electron Microscopy to Assess Histopathological Resolution of Class V Lupus Nephritis: A Case Report.

Lupus nephritis (LN) is most frequently associated with poor outcomes in patients with systemic lupus erythematosus (SLE). LN manifests as histopathological changes in the kidney caused by immune complex formation and deposition. In particular, immunoglobulin G (IgG) deposits are frequently observed by immunofluorescence staining, which helps to establish the diagnosis of LN. In this case report, we describe a 57-year-old woman with SLE who had been undergoing treatment on an outpatient basis for 11 years. Her first and second renal biopsies revealed class V LN with a coarsely granular pattern of IgG deposition in the peripheral capillary walls. However, her third renal biopsy showed no IgG deposition, which indicated histopathological resolution of her class V LN. We used low-vacuum scanning electron microscopy (LV-SEM) to examine the three-dimensional structural alterations in her glomerular basement membranes. In this report, we describe findings that indicated resorption of epithelial deposits, that is, resolution of LN. The results of repeated kidney biopsies confirmed by LV-SEM suggested the possibility of a state unrelated to LN.

Chronic kidney disease caused by maternally inherited diabetes and deafness: a case report.

Maternally inherited diabetes and deafness (MIDD) is a mitochondrial genetic disorder with variable clinical presentations, which can delay its diagnosis. Herein, we report the case of a 57-year-old Japanese man with MIDD who developed chronic kidney disease. He developed proteinuria long before his diabetes and deafness; at the age of 36 years, a renal biopsy showed minor glomerular abnormality and electron microscopy showed mild mitochondrial degeneration in the distal tubular epithelial cells. Twenty years later, a second renal biopsy showed nephrosclerosis with interstitial fibrosis and arteriolar hyaline thickening, despite the absence of hypertension and relatively good glycemic control. Granular swollen epithelial cells were found in the medullary collecting duct epithelium. Electron microscopy showed accumulating mitochondria in podocytes and tubular cells, leading to the diagnosis of MIDD. A muscle biopsy also showed ragged-red fibers, despite the absence of muscle weakness. Mitochondrial DNA analysis revealed an m.3243A > G mutation, and taurine supplementation was initiated. Our findings suggest that mitochondrial dysfunction is mainly associated with progressive renal damage.

Nanostructured lipid carriers as a novel tool to deliver sclareol: physicochemical characterisation and evaluation in human cancer cell lines

Sclareol (SC) is arousing great interest due to its cytostatic and cytotoxic activities in several cancer cell lines. However, its hydrophobicity is a limiting factor for its in vivo administration. One way to solve this problem is through nanoencapsulation. Therefore, solid lipid nanoparticles (SLN-SC) and nanostructured lipid carriers (NLC-SC) loaded with SC were produced and compared regarding their physicochemical properties. NLC-SC showed better SC encapsulation than SLN-SC and was chosen to be compared with free SC in human cancer cell lines (MDA-MB-231 and HCT-116). Free SC had slightly higher cytotoxicity than NLC-SC and produced subdiploid DNA content in both cell lines. On the other hand, NLC-SC led to subdiploid content in MDA-MB-231 cells and G2/M checkpoint arrest in HCT-116 cells. These findings suggest that SC encapsulation in NLC is a way to allow the in vivo administration of SC and might alter its biological properties

Encapsulation of camu-camu extracts using prebiotic biopolymers: Controlled release of bioactive compounds and effect on their physicochemical and thermal properties.

Camu-camu (Myrciaria dubia [H.B.K] McVaugh) is a Amazonian fruit rich in ascorbic acid and phenolic compounds, and has been attracting great interest from the food, pharmaceutical and nutraceutical industries due to its potential health benefits. The bioactive compounds from camu-camu are considered sensitive and unstable, resulting in nutritional losses and impairment of its commercialization and export. For this reason, the camu-camu extract (pulp and peel) was subjected to microencapsulation by spray drying process using maltodextrin (MD), inulin (IN), and oligofructose (OL) as carrier agents. Lyophilized in natura camu-camu extract (CEL) was also evaluated. Thus, physicochemical and thermal properties and controlled release at different temperatures (25 °C and 35 °C) were investigated. In contrast with the IN and OL microparticles, the MD microparticles showed lower density and hygroscopicity, besides greater thermal stability, antioxidant activity, and retention of ascorbic acid and anthocyanins. FTIR spectra allowed the qualitative evidence of encapsulation of the bioactive compounds from the camu-camu extract. The highest percentage of volatile compounds was observed in IN microparticles, followed by OL and MD microparticles. The major group of compounds identified in CEL were terpenes (88%). The Korsmeyer-Peppas mathematical model allowed to describe the controlled release behavior of ascorbic acid and anthocyanins in the powder extracts. The controlled release followed a Fickian diffusion mechanism (n ≤ 0.43). The increase of temperature from 25 °C to 35 °C influenced on the release of bioactive compounds in all treatments, showing greater release for MD microparticles. The encapsulating materials were considered effective for the production of camu-camu extract powder, contributing to the better use of this Amazonian fruit. In addition, the encapsulation process increased the stability of its bioactive compounds, representing a tool to facilitate their incorporation in several matrices to act as antioxidant and coloring agents, as well as nutraceutical.

Novel self-nanoemulsifying drug-delivery system enhances antileukemic properties of all-trans retinoic acid.

Aim: All-trans retinoic acid (ATRA) shows erratic oral bioavailability when administered orally against leukemia, which can be solved through its incorporation in self-nanoemulsifying drug-delivery systems (SEDDS). The SEDDS developed contained a hydrophobic ion pair between benzathine (BZT) and ATRA and was enriched with tocotrienols by the input of a palm oil tocotrienol rich fraction (TRF) in its composition. Results: SEDDS-TRF-ATRA-BZT allowed the formation of emulsions with nanometric size that retained ATRA within their core after dispersion. Pharmacokinetic parameters after oral administration of SEDDS-TRF-ATRA-BZT in mice were improved compared with what was seen for an ATRA solution. Moreover, SEDDS-TRF-ATRA-BZT had improved activity against HL-60 cells compared with SEDDS without TRF. Conclusion: SEDDS-TRF-ATRA-BZT is a promising therapeutic choice over ATRA conventional medicine.

Chitosan/hydroxyethyl cellulose inserts for sustained-release of dorzolamide for glaucoma treatment: In vitro and in vivo evaluation.

Eye drops containing hydrophilic drugs are commonly used to reduce intraocular pressure (IOP) in glaucoma patients, but compliance to the treatement is commonly reduced by frequent dosing and eventual systemic side effects. Sustained-release drug delivery systems, such as ocular inserts, can reduce dosing, limit systemic exposure, reduce side effects, and, then, improve patient adherence to therapy. Here, we developed and evaluated chitosan/hydroxyethyl cellulose-based ocular inserts for sustained release of dorzolamide, a hydrophilic drug. Dorzolamide inserts (DI) were produced by solvent/casting method and characterized by various physicochemical techniques. Pharmacokinetics studies were performed using scintigraphic images and ex vivo biodistribution. The effectiveness of inserts was tested in glaucomatous rats. Characterization studies showed that the drug strongly interacted with the polymeric matrix, but in vitro results showed that DI took only 3 h to release 75% of dorzolamide entraped. However, scintigraphic images and ex vivo biodistribution studies revealed that more than 50% of 99mTc-dorzolamide remained in the eye after 18 h of DI administration, while only about 30% of the drug remained in the eye after drops instilation. DI exerted significant hypotensive effect for two weeks, after single administration, while IOP values remained high in placebo and untreated groups. Eye drops were effective only during the treatment period. Only DI treatment prevented retinal ganglion cells death. Altogether, these findings evidenced the potential application of polymeric-based inserts for sustained release of dorzolamide in glaucoma management.

Sclareol is a potent enhancer of doxorubicin: Evaluation of the free combination and co-loaded nanostructured lipid carriers against breast cancer.

AIMS: In this work, it was sought to determine if there was synergism between doxorubicin (DOX), a well-known antineoplastic, and sclareol (SC), a diterpene from natural origin, in breast cancer treatment. Moreover, it was investigated if their co-loading in the same nanocarrier would result in a gain of activity and/or a toxicity diminishment. MAIN METHODS: The synergism of the DOX:SC combination was evaluated in MDA-MB-231 and 4T1 cells. A nanostructured lipid carrier (NLC) co-encapsulating DOX and SC in their synergistic molar ratio was prepared and characterised, in terms of mean diameter, zeta potential, DOX encapsulation efficiency, small angle X-ray scattering, differential scanning calorimetry, and polarised light microscopy for further intravenous administration. The anticancer activity of the combination, free and encapsulated, was evaluated in 4T1-tumour bearing mice. KEY FINDINGS: It was determined that DOX:SC combination at the molar ratio 1:1.9 presents better synergistic anticancer activity than the molar ratio 1:7.5 in vitro. DOX:SC-loaded NLC (NLC-DOX-SC) improved in vitro cytotoxic and in vivo antitumour activity compared to free DOX. Although NLC-DOX-SC and free DOX:SC, at the synergistic molar ratio, showed similar activity in the in vivo study, the free combination provoked body weight loss, behaviour alterations and haematological toxicity in the animals, while this was not observed for NLC-DOX-SC. SIGNIFICANCE: This work shows that SC and DOX present synergistic anticancer activity for breast cancer treatment whereas NLC-DOX-SC was a feasible alternative to attain the benefits posed by DOX:SC combination but with none to fewer side effects.

ß-Cyclodextrin inclusion complexes with essential oils: Obtention, characterization, antimicrobial activity and potential application for food preservative sachets.

The current study aimed obtaining antimicrobial sachets that could be used as preservatives for foods. Basil (BEO) and Pimenta dioica (PDEO) essential oils (EOs) were analyzed by GC-FID and GC-MS and tested against the foodborne bacteria S. aureus, E. coli, L. monocytogenes, P. aeruginosa, S. Enteritidis, and the food-spoilage mold B. nivea. Then, inclusion complexes (ICs) with EOs and ß-cyclodextrin (ß-CD) were prepared as a strategy to reduce volatility and increase the release time of EOs. Eight ICs were prepared by kneading and freeze-drying methods, in two molar ratios, and have been characterized by complementary methods: FT-IR, thermal analysis (DSC and TG/DTG), powder XRD, and solid state 13C NMR. In vitro antimicrobial activities of ICs, both dispersed in agar and loaded in sachets, have also been investigated. Complexation was confirmed for all samples. PDEO-based ICs prepared by kneading method, at both molar ratios, displayed better in vitro antimicrobial activity. The obtained results strongly suggest a potential application of these ICs as natural antimicrobials.

Polymorphic characterization and implications on biopharmaceutics properties of potential anti-inflammatory drug candidate eremantholide C from Lychnophora trichocarpha (Brazilian Arnica).

OBJECTIVES: To perform the polymorphic and physicochemical characterization of the potential anti-inflammatory drug, eremantholide C (EREC), as well as to evaluate the influence of these characteristics on its biopharmaceutics classification. METHODS: Eremantholide C was obtained from chloroformic extract of Lychnophora trichocarpha and crystallized in two distinct solvents: chloroform (EREC 1) and ethyl acetate (EREC 2). To evaluate the polymorphism, EREC samples were submitted to melting point, purity, infrared spectroscopy, differential scanning calorimetry (DSC), X-ray powder diffraction, optical microscopy and scanning electron microscopy analysis. In addition, EREC samples crystallized after intrinsic dissolution study were submitted to DSC and X-ray powder diffraction analysis. KEY FINDINGS: EREC 1 showed fusion at 234.7-241.6 °C, while EREC 2 showed fusion at 238.6-243.7 °C. No polymorphic transitions were observed during the intrinsic dissolution experiment. A single sharp endothermic peak was obtained for the EREC samples. X-ray diffraction showed no crystallographic differences between the EREC samples. EREC 1 and EREC 2 showed birefringence under polarized light and indefinite morphology; however, the shape of the crystals was common to the two samples. CONCLUSIONS: Eremantholide C does not present classical or morphological polymorphism; therefore, there is no influence of crystalline transitions in the solubility and consequently in its biopharmaceutics classification and oral absorption process.