Jessica Mendes Nadal

An innovative quaternary ammonium methacrylate polymer can provide improved antimicrobial properties for a dental adhesive system.

A quaternary ammonium methacrylate polymer (QAMP) with antimicrobial potential was synthesized. The resulting product (QAMP) was characterized by FTIR spectroscopy, NMR spectroscopy, visible spectrophotometry, XRPD and TGA. The in vitro susceptibility tests against Streptococcus mutans of QAMP were investigated prior and after incorporation into a commercial adhesive system (Clearfil™ SE Bond). The release of quaternary ammonium compounds from the experimental adhesive system (Clearfil™ SE Bond + 5% QAMP) was performed during 1, 7, 14, 21 and 30 days. Spectroscopic data confirmed that QAMP was successfully obtained. Thermogravimetric analysis indicated that QAMP was heat stable. Prior incorporation into the adhesive system, QAMP revealed an inhibition halo of 18.33 ± 0.6 mm. By agar disk diffusion test, Clearfil™ SE Bond containing 5% QAMP presented an inhibition halo (16.67 ± 1.5 mm) similar to Clearfil™ Protect Bond (positive control, 17.00 ± 1.7, p = 0.815) and significantly higher than Clearfil™ SE Bond (negative control, 11.00 ± 1.0, p = 0.006). The minimum inhibitory/bactericidal concentrations for Clearfil™ SE Bond containing 5% QAMP were 20 μL mL−1. The release of quaternary ammonium compounds from the experimental adhesive containing QAMP was very low (5.1%) when compared to Clearfil™ Protect Bond that released 47.2% of its quaternary ammonium monomer (MDPB) after 30 days. The QAMP can offer enhanced antimicrobial properties for self-etching adhesive systems.

Effect of a Novel Quaternary Ammonium Methacrylate Polymer (QAMP) on Adhesion and Antibacterial Properties of Dental Adhesives

This study investigated the resin–dentin bond strength (μTBS), degree of conversion (DC), and antibacterial potential of an innovative adhesive system containing a quaternary ammonium methacrylate polymer (QAMP) using in situ and in vitro assays. Forty-two human third molars were flattened until the dentin was exposed and were randomly distributed into three groups of self-etching adhesive systems: Clearfil™ SE Bond containing 5% QAMP (experimental group), Clearfil™ Protect Bond (positive control) and Clearfil™ SE Bond (negative control). After light curing, three 1 mm-increments of composite resin were bonded to each dentin surface. A total of thirty of these bonded teeth (10 teeth per group) was sectioned to obtain stick-shaped specimens and tested under tensile stress immediately, and after 6 and 12 months of storage in distilled water. Twelve bonded teeth (4 teeth per group) were longitudinally sectioned in a mesio-to-distal direction to obtain resin-bonded dentin slabs. In situ DC was evaluated by micro-Raman spectroscopy. In vitro DC of thin films of each adhesive system was measured using Fourier transform infrared spectroscopy. In vitro susceptibility tests of these three adhesive systems were performed by the minimum inhibitory/minimum bactericidal concentration (MIC/MBC) assays against Streptococcus mutans, Lactobacillus casei, and Actinomyces naeslundii. No statistically significant difference in μTBS was observed between Clearfil™ SE Bond containing 5% QAMP and Clearfil™ SE Bond (p > 0.05) immediately, and after 6 and 12 months of water storage. However Clearfil™ Protect Bond showed a significant reduction of μTBS after 12 months of storage (p = 0.039). In addition, QAMP provided no significant change in DC after incorporating into Clearfil™ SE Bond (p > 0.05). Clearfil™ SE Bond containing 5% QAMP demonstrated MIC/MBC values similar to the positive control against L. casei and A. naeslundii and higher than the negative control for all evaluated bacterial strains. The use of QAMP in an adhesive system demonstrated effective bond strength, a suitable degree of conversion, and adequate antibacterial effects against oral bacteria, and may be useful as a new approach to provide long-lasting results for dental adhesives.

Enhanced gastric tolerability and improved anti-obesity effect of capsaicinoids-loaded PCL microparticles.

Capsaicinoids show several pharmacological effects including weight loss. However, their pungency limits the long-term use through the gastrointestinal tract. In that sense, the goal of this study was to prepare capsaicinoids-loaded poly(ε-caprolactone) microparticles as an oral carrier in order to improve their gastric tolerability and to make feasible the long-term treatment of obesity. Formulations containing 3, 5 and 10% capsaicinoids were successfully obtained by simple emulsion/solvent evaporation method. Values of encapsulation efficiency above 90% were achieved. Microparticles showed spherical shape and smooth surface. The particle size was suitable for oral use in order to provide an extended release through the gastrointestinal tract. No chemical bond was observed between drug and polymer. Microencapsulation led to drug amorphization. Formulations prolonged the release of capsaicinoids without changing the release kinetic (biexponential model). Microencapsulation increased the gastric tolerability of capsaicinoids because it prevented inflammatory processes in the stomach of rats. Microparticles containing 5% capsaicinoids demonstrated a statistically significant reduction of Lee index, mesenteric and retroperitoneal fat pads of rats with obesity induced by hypothalamic lesion using monosodium l-glutamate. In summary, capsaicinoids-loaded poly(ε-caprolactone) microparticles are low-irritative oral controlled-release carriers for a long-term use in obesity.

Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect

This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3μm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects.

Spray-dried solid dispersions containing ferulic acid: comparative analysis of three carriers, in vitro dissolution, antioxidant potential and in vivo anti-platelet effect

Abstract This article aimed to improve the relative solubility and dissolution rate of ferulic acid (FA) by the use of spray-dried solid dispersions (SDs) in order to ensure its in vitro antioxidant potential and to enhance its in vivo anti-platelet effect. These SDs were prepared by spray-drying at 10 and 20% of drug concentration using polyvinylpyrrolidone K30 (PVP-K30), polyethylene glycol 6000 (PEG 6000) and poloxamer-188 (PLX-188) as carriers. SDs and physical mixtures (PM) were characterized by SEM, XRPD, FTIR spectroscopy and TGA analysis. Spray-dried SDs containing FA were successfully obtained. Relative solubility of FA was improved with increasing carrier concentration. PVP-K30 and PEG 6000 formulations showed suitable drug content values close to 100%, whereas PLX-188 presented mean values between 70 and 90%. Agglomerates were observed depending on the carrier used. XRPD patterns and thermograms indicated that spray-drying led to drug amorphization and provided appropriate thermal stability, respectively. FTIR spectra demonstrated no remarkable interaction between carrier and drug for PEG 6000 and PLX-188 SDs. PVP-K30 formulations had changes in FTIR spectra, which denoted intermolecular O–H•••O = C bonds. Spray-dried SDs played an important role in enhancing dissolution rate of FA when compared to pure drug. The free radical-scavenging assay confirmed that the antioxidant activity of PEG 6000 10% SDs was kept. This formulation also provided a statistically increased in vivo anti-platelet effect compared to pure drug. In summary, these formulations enhanced relative solubility and dissolution rate of FA and chosen formulation demonstrated suitable in vitro antioxidant activity and improved in vivo anti-platelet effect.

A Stability-Indicating HPLC-DAD Method for Determination of Ferulic Acid into Microparticles: Development, Validation, Forced Degradation, and Encapsulation Efficiency

A simple stability-indicating HPLC-DAD method was validated for the determination of ferulic acid (FA) in polymeric microparticles. Chromatographic conditions consisted of a RP C18 column (250 mm × 4.60 mm, 5 μm, 110 Å) using a mixture of methanol and water pH 3.0 (48 : 52 v/v) as mobile phase at a flow rate of 1.0 mL/min with UV detection at 320 nm. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of quantification, limit of detection, accuracy, precision, and robustness provided suitable results regarding all parameters investigated. The calibration curve was linear in the concentration range of 10.0–70.0 μg/mL with a correlation coefficient >0.999. Precision (intraday and interday) was demonstrated by a relative standard deviation lower than 2.0%. Accuracy was assessed by the recovery test of FA from polymeric microparticles (99.02% to 100.73%). Specificity showed no interference from the components of polymeric microparticles or from the degradation products derived from acidic, basic, and photolytic conditions. In conclusion, the method is suitable to be applied to assay FA as bulk drug and into polymeric microparticles and can be used for studying its stability and degradation kinetics.

Nanocapsules improve indole-3-carbinol photostability and prolong its antinociceptive action in acute pain animal models

ABSTRACT This study aimed the development of nanocapsules (NCs) for oral indole‐3‐carbinol (I3C) administration and evaluation of antinociceptive potential of this compound in its two forms, free and nanoencapsulated, using acute pain models. NCs showed adequate physicochemical characteristics and protected the I3C against UVC radiation exposure. It was observed no chemical bond between I3C and polymer by FTIR. Besides, X‐ray and DSC analysis suggested that I3C was molecularly dispersed in NCs. The dialysis bag technique showed that almost 100% of the compound was released from NCs at 360 min. Mathematical modeling demonstrated that this release occurred in two rates, with an initial burst effect followed by a slower release of I3C. Regarding the in vivo analysis, time‐response curve showed that both forms of I3C caused an inhibition in inflammatory phase of nociception induced by formalin and increased the latency response in hot plate test. Interestingly, NCs were able to prolong the I3C effect in both tests. Furthermore, in dose‐response curve, only I3C in its nanoencapsulated form presented effect on inflammatory phase of the formalin test. In conclusion, NCs to I3C incorporation presented adequate nanometric characteristics and prolonged its antinociceptive action in acute pain models tested. Graphical abstract Figure. No Caption available.

Evaluation of larvicidal activity and ecotoxicity of linalool, methyl cinnamate and methyl cinnamate/linalool in combination against Aedes aegypti

The frequent use of synthetic pesticides to control Aedes aegypti population can lead to environmental and/or human contamination and the emergence of resistant insects. Linalool and methyl cinnamate are presented as an alternative to the synthetic pesticides, since they can exhibit larvicidal, repellent and/or insecticidal activity and are considered safe for use. The aim of this study was to evaluate the larvicidal activity of methyl cinnamate, linalool and methyl cinnamate/linalool in combination (MC-L) (1:4 ratio, respectively) against Aedes aegypti. The in vitro preliminary toxicity through brine shrimp lethality assay and hemolytic activity, and the phytotoxic potential were also investigated to assess the safety of their use as larvicide. Methyl cinnamate showed significant larvicidal activity when compared to linalool (LC50 values of 35.4µg/mL and 275.2µg/mL, respectively) and to MC-L (LC50 138.0µg/mL). Larvae morphological changes subjected to the specified treatments were observed, as the flooding of tracheal system and midgut damage, hindering the larval development and survival. Preliminary in vitro toxicity through brine shrimp showed the high bioactivity of the substances (methyl cinnamate LC50 35.5µg/mL; linalool LC50 96.1µg/mL) and the mixture (MC-L LC50 57.7µg/mL). The results showed that, despite the higher larvicidal activity of methyl cinnamate, the use of MC-L as a larvicide seems to be more appropriate due to its significant larvicidal activity and low toxicity.

Effect on vascular permeability of a self-etching adhesive system containing an antimicrobial quaternary ammonium polymer QAMP into subcutaneous tissue of rats

OBJECTIVE This study investigated the effect of a self-etching adhesive system containing an antimicrobial quaternary ammonium methacrylate polymer (QAMP) on the vascular permeability using Evans blue and laser-Doppler flowmetric methods. DESIGN Forty rats were anesthetized and divided into groups: saline solution; Clearfil™ Protect Bond; Clearfil™ SE Bond; Clearfil™ SE Bond containing QAMP. Injections of Evans blue were administrated intravenously and the substances were injected intradermally. Immediately before injection and after 3 and 6h, was evaluated the blood flow. The animals were killed 3 and 6h after injection. The dorsal skin was dissected and experimental sites were obtained. The vascular permeability was evaluated by dye extravasation area, the dye was extracted and absorbance measured. RESULTS Concerning the Evans blue method, Clearfil™ SE Bond containing QAMP showed an extravasation area statistically similar to Clearfil™ SE Bond and lower than Clearfil™ Protect Bond. No statistical difference was verified among experimental groups for the amount of dye extracted. Clearfil™ SE Bond containing QAMP provided better laser-Doppler flowmetric parameters than Clearfil™ Protect Bond immediately and 3h after injection. CONCLUSION The QAMP had lower effect on the exudative phase of the inflammatory process.

Long-lasting anti-platelet activity of cilostazol from poly(ε-caprolactone)-poly(ethylene glycol) blend nanocapsules

Cilostazol (CLZ) acts as a vasodilator and antiplatelet agent and is the main drug for the treatment of intermittent claudication (IC) related to peripheral arterial disease (PAD). The usual oral dose is 100 mg twice a day, which represents a disadvantage in treatment compliance. CLZ presents several side effects, such as headache, runny nose, and dizziness. This paper aimed to obtain novel polymeric nanocapsules prepared from poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG) blend containing CLZ. Nanocapsules showed pH values between 6.1 and 6.3, average size lower than 137 nm, low polydispersity index (<0.22) and negative zeta potential. These nanoformulations demonstrated spherical shape with smooth surface. Results achieved by X-ray diffraction (XRD) and differential scanning calorimetry (DSC) indicated drug amorphization compared to pure CLZ. Fourier-transformed infrared spectroscopy (FTIR) showed no chemical bonds between drug and polymers. Formulations presented suitable stability for physical parameters. The in vitro drug release demonstrated prolonged release with no burst effect. Drug release was controlled by both mechanisms of polymer relaxation/degradation and Fickian diffusion. Moreover, chosen CLZ-loaded nanocapsules provided an in vivo prolonged antiplatelet effect for CLZ statistically similar to aspirin. These formulations can be further used as a feasible oral drug delivery carrier for controlled release of CLZ in order to treat PAD and IC events.