Coumarin/ß-Cyclodextrin Inclusion Complexes Promote Acceleration and Improvement of Wound Healing.

Coumarins have great pharmacotherapeutic potential, presenting several biological and pharmaceutical applications, like antibiotic, fungicidal, anti-inflammatory, anticancer, anti-HIV, and healing activities, among others. These molecules are practically insoluble in water, and for biological applications, it became necessary to complex them with cyclodextrins (CDs), which influence their bioavailability in the target organism. In this work, we studied two coumarins, and it was possible to conclude that there were structural differences between 4,7-dimethyl-2H-chromen-2-one (DMC) and 7-methoxy-4-methyl-2H-chromen-2-one (MMC)/ß-CD that were solubilized in ethanol, frozen, and lyophilized (FL) and the mechanical mixtures (MM). In addition, the inclusion complex formation improved the solubility of DMC and MMC in an aqueous medium. According to the data, the inclusion complexes were formed and are more stable at a molar ratio of 2:1 coumarin/ß-CD, and hydrogen bonds along with π-π stacking interactions are responsible for the better stability, especially for (MMC)2@ß-CD. In vivo wound healing studies in mice showed faster re-epithelialization and the best deposition of collagen with the (DMC)2@ß-CD (FL) and (MMC)2@ß-CD (FL) inclusion complexes, demonstrating clearly that they have potential in wound repair. Therefore, (DMC)2@ß-CD (FL) deserves great attention because it presented excellent results, reducing the granulation tissue and mast cell density and improving collagen remodeling. Finally, the protein binding studies suggested that the anti-inflammatory activities might exert their biological function through the inhibition of MEK, providing the possibility of development of new MEK inhibitors.

Development and validation of analytical methods by HPLC for quality control of avermectins and milbemycins in bulk samples

This work aims to develop analytical methods using high-performance liquid chromatography with a diode array detector (HPLC-DAD) for analysis and quantification of avermectins (AVMs) and milbemycins (MBMs) in bulk samples. First, the methods were optimized and some parameters such as temperature, flow rate, injection volume and mobile phase with different proportions of solvents were evaluated. The best chromatographic conditions were obtained using the Phenomenex® C18 (150 × 4.60 mm, 5 µm) column at a temperature of 20 °C, flow rate of 1.2 mL min-1, injection volume of 20 µL, and detection at 250 nm. Acetonitrile: ultrapure water (87: 13, v/v) was used as mobile phase for moxidectin and eprinomectin, and acetonitrile: methanol: ultrapure water (53: 35: 12, v/v/v) for abamectin and ivermectin. Under these conditions satisfactory results were obtained, with appropriate limits of detection and quantification, acceptable linearity, precision, accuracy, and robustness. These methods satisfy the need for analytical methods for the multi-determination of MBMs and the B1a and B1b forms of AVMs by HPLC-DAD, which can be considered simple, effective, innovative and should aid in the development of the fiel

Synthesis of mesoporous magnetic polypyrrole and its application in studies of removal of acidic, neutral, and basic pharmaceuticals from aqueous medium.

As an alternative to traditional adsorbents, mesoporous magnetic polypyrrole (MMPPy) was first used as an adsorbent for the removal of acid, neutral, and basic pharmaceutical compounds considered aqueous pollutants. Ibuprofen (IBU, acid), caffeine (CAF, neutral), and bupropion (BUP, basic) were chosen as adsorbates and applied in adsorption studies. They proved to be pH dependent of the aqueous solution and the best results were found at pH 4 for IBU and CAF and pH 7 for BUP and 60 mg was the optimal amount of adsorbent to be used in the studies. Adsorption was extremely fast and the equilibrium was reached up to 180 s. The adsorption data of all analytes could be well interpreted by the pseudo second-order kinetic model and the dual-site Langmuir-Freundlich isotherm model. The adsorption capacities obtained by the dual-site Langmuir-Freundlich model were 53.67 mg g-1, 16.74 mg g-1, and 24.72 mg g-1 for IBU, CAF, and BUP, respectively. Thermodynamic parameters revealed that IBU adsorption becomes spontaneous as temperature increases and CAF and BUP adsorption occurs through a non-spontaneous process. In addition, this study shows endothermic nature of the adsorption process. Analytes were desorbed using an aqueous solution at pH 10 for IBU, pH 7 for CAF, and pH 4 for BUP and then the material was regenerated successfully. The results suggest that MMPPy can be efficiently used in the removal of different organic analytes found in contaminated water.

Pipette-tip solid-phase extraction using poly(1-vinylimidazole-co-trimethylolpropane trimethacrylate) as a new molecularly imprinted polymer in the determination of avermectins and milbemycins in fruit juice and water samples.

A simple HPLC method was developed for the determination of abamectin (ABA), eprinomectin (EPR), and moxidectin (MOX). Pipette-tip molecularly imprinted polymer solid-phase extraction (PT-MIP-SPE) using poly(1-vinylimidazole-co-trimethylolpropane trimethacrylate) as a selective adsorbent material was studied in detail, including the washing solvent, type and volume of eluent, pH, quantity of adsorbent material and sample volume. The performance criteria for linearity, sensitivity, precision, accuracy, recovery, robustness and stability have been assessed and were within the recommended guidelines. The mean extraction recoveries/relative standard deviation for ABA 1b, EPR, ABA 1a and MOX were 98.77 ±â€¯3.82%, 88.19 ±â€¯2.57%, 110.54 ±â€¯1.52% and 100.42 ±â€¯0.59%, respectively. Finally, the results proved that PT-MIP-SPE coupled to HPLC-UV is an economical, simple and easy-to-perform technique, and presented a high potential for extraction of macrocyclic lactones in mineral water and grape and juice samples.

Functional polyaniline/multiwalled carbon nanotube composite as an efficient adsorbent material for removing pharmaceuticals from aqueous media.

The composite polyaniline/multiwalled carbon nanotube (PAni/MWCNT, 1:0.1 w/w) was developed with the intention of binding the adsorbent properties of two materials and using it to adsorb pharmaceuticals from aqueous media. PAni/MWCNT was characterized by scanning electron microscopy, thermogravimetry, infrared spectroscopy, pH at the point of zero charge, and the effect on the surface wettability of the material. As proof of concept, adsorption studies were carried out using meloxicam (MLX) as the pharmaceutical and it was evaluated as a function of pH, temperature, ionic strength, contact time and variation in concentration. Kinetics and isothermal models were applied to evaluate the mechanism of the adsorption process. The best MLX adsorption result was at pH 2 with 6 min of contact with PAni/MWCNT. The kinetics models that fitted the experimental data were pseudo-second order and Elovich and the kinetics model was the dual-site Langmuir-Freundlich. Both models suggest that the adsorption occurs by the chemical nature of the surface and in the pores of the energetically heterogeneous composite. The PAni/MWCNT presented an adsorption capacity of 221.2 mg g-1, a very good value when compared with the literature and can be used to remove pharmaceuticals from aqueous environments.

Pipette-tip solid-phase extraction using polypyrrole as efficient adsorbent for extraction of avermectins and milbemycins in milk.

In this work, we developed a HPLC method for the multidetermination of avermectins (AVM) (abamectin-ABA 1b and ABA 1a, eprinomectin-EPR, and ivermectin-IVM) and milbemycins (moxidectin-MOX) in milk samples using polypyrrole (PPy) as adsorbent material in pipette-tip solid-phase extraction (PT-PPy-SPE). PPy was characterized by scanning electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, and X-ray diffraction and the data agreed with the literature. The sample preparation included the clean-up of the milk by protein precipitation (PP) with acetonitrile and extraction of the analytes by PT-PPy-SPE. The chromatographic method was developed in reverse phase and isocratic mode with flow rate at 1.2 mL min-1 and ultraviolet detection at 250 nm. The mobile phase composition was acetonitrile:methanol:water (55:25:20, v/v/v). The studied parameters and the optimized conditions for the sample preparation were washing solvent (300 µL water), volume and type of eluent (500 µL methanol), volume and pH of sample (1 mL and pH 10), amount of adsorbent material (50 mg PPy), and without addition of salt (NaCl). The method was linear over the concentration range from 20 to 3000 ng mL-1 with coefficients of correlation (r) ≥ 0.99 for all analytes and recoveries around 100%. The method developed and validated was used for the analyses of real milk samples from cow treated with Ivomec® (IVM 3.5%), in which were found 21.51 ± 2.94 ng mL-1 of IVM. Finally, the results proved that PT-PPy-SPE coupled to HPLC-UV was economical, simple, and easy-to-perform technique. Graphical abstract Pipette-tip solid phase extraction using polypirrole as adsorbent material for determination of avermectins and milbemycins in milk.