Micro-Injection Moulding of PEO/PCL Blend-Based Matrices for Extended Oral Delivery of Fenbendazole.

Fenbendazole (FBZ) is a broad-spectrum anthelmintic administered orally to ruminants; nevertheless, its poor water solubility has been the main limitation to reaching satisfactory and sustained levels at the site of the target parasites. Hence, the exploitation of hot-melt extrusion (HME) and micro-injection moulding (µIM) for the manufacturing of extended-release tablets of plasticised solid dispersions of poly(ethylene oxide) (PEO)/polycaprolactone (PCL) and FBZ was investigated due to their unique suitability for semi-continuous manufacturing of pharmaceutical oral solid dosage forms. High-performance liquid chromatography (HPLC) analysis demonstrated a consistent and uniform drug content in the tablets. Thermal analysis using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) suggested the amorphous state of the active ingredient, which was endorsed by powder X-ray diffraction spectroscopy (pXRD). Fourier transform infrared spectroscopy (FTIR) analysis did not display any new peak indicative of either a chemical interaction or degradation. Scanning electron microscopy (SEM) images showed smoother surfaces and broader pores as we increased the PCL content. Electron-dispersive X-ray spectroscopy (EDX) revealed that the drug was homogeneously distributed within the polymeric matrices. Drug release studies attested that all moulded tablets of amorphous solid dispersions improved the drug solubility, with the PEO/PCL blend-based matrices showing drug release by Korsmeyer-Peppas kinetics. Thus, HME coupled with µIM proved to be a promising approach towards a continuous automated manufacturing process for the production of oral solid dispersions of benzimidazole anthelmintics to grazing cattle.

Nanocellulose for peripheral nerve regeneration in rabbits using citric acid as crosslinker with chitosan and freeze/thawed PVA.

This work investigates peripheral nerve regeneration using membranes consisting of pure chitosan (CHI), which was further blended with nanofibrillated cellulose, with citric acid as crosslinker, with posterior addition of polyvinyl alcohol, with subsequent freeze thawing. Nanocellulose improves the mechanical and thermal resistance, as well as flexibility of the film, which is ideal for the surgical procedure. The hydrogel presented a slow rate of swelling, which is adequate for cell and drug delivery. A series ofin vitrotests revealed to be non-toxic for neuronal Schwann cell from the peripheral nervous system of Rattus norvegicus, while there was a slight increase in toxicity if crosslink is performed-freeze-thaw. Thein vivoresults, using rabbits with a 5 mm gap nerve defect, revealed that even though pure CHI was able to regenerate the nerve, it did not present functional recovery with only the deep pain attribute being regenerated. When autologous implant was used jointly with the biomaterial membrane, as a covering agent, it revealed a functional recovery within 15 d when cellulose and the hydrogel were introduced, which was attributed to the film charge interaction that may help influence the neuronal axons growth into correct locations. Thus, indicating that this system presents ideal regeneration as nerve conduits.

Antioxidant, antibacterial and antitumoural activities of kraft lignin from hardwood fractionated by acid precipitation.

Kraft lignin, so far useful for energy generation, has been gathering considerable attention as an alternative material to replace fossil-based resources mainly due to its high phenolic content. However, the wide molecular weight distribution and chemical composition heterogeneity led to the development of fractionation methods. Herein, to narrow such characteristics we used eucalypt kraft lignin fractionated at pH's 9, 7, 5 and 3 by sequential acid precipitation. These lignin fractions were first characterised by simultaneous pyrolysis and trimethylsilylation (SPyT) with N-Methyl-N-(trimethylsilyl) trifluoroacetamide with posterior tests of antioxidant, antibacterial, and antitumour activities. We observed higher ratio of syringyl/guaiacyl groups and increase in antioxidant activity in those fractions with lower molecular weight (precipitated at lower pH's). Fractions precipitated at pH's 9 and 7 have shown an outstanding antibacterial activity against five bacteria. Moreover, fractions 7 and 5 presented at cytotoxicity tests higher ability to inhibit the growth of U87MG and T98G glioma cells, while only a slight inhibition of adult human fibroblasts (non-tumour cells) was detected.

Synthesis and in vivo evaluation of a scaffold containing wollastonite/ß-TCP for bone repair in a rabbit tibial defect model.

Scaffolds are models designed to aid the interaction between cells and extracellular bone matrix, providing structural support for newly formed bone tissue. In this work, wollastonite with ß-TCP porous ceramic scaffolds was developed by the polymer sponge replication. Their microstructure, cell viability and bioactivity were tested. in vivo was performed to evaluate the use of a calcium silicate-based implant in the repair of rabbit tibias. Holes were made in the both proximal and distal tibial metaphysis of each animal and filled with calcium silicate-based implant, and in the left tibia, no implant were used, serving as control group. Animals underwent euthanasia after 30 and 60 days of study. The animals were submitted to clinical-radiographic evaluations and their histology was analyzed by optical and scanning electron microscope. The studied calcium silicate implant provided biocompatibility and promoted bone formation, stimulating the process of bone repair in rabbits, features observed by gradual radiopacity shown in the radiographic evaluations.

Synthesis and in Vivo Behavior of PVP/CMC/Agar Hydrogel Membranes Impregnated with Silver Nanoparticles for Wound Healing Applications.

The field of wound healing has seen an increase in research activity in wound care and hydrogel-based dressings have been targeted as a solution for these applications. Hydrogels with silver nanoparticles can present many advantages for this field. However, if the aggregation and sterilization of this product have not been carefully considered, the effectiveness or use could be limited. Therefore, in the current study, a hydrogel-based wound dressing membrane was developed using polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), agar, and carboxymethyl cellulose (CMC). Silver ions (Ag+) were dispersed in the polymer matrix and its reduction with formation of a hydrogel and silver nanoparticles was performed using 60Co gamma irradiation to enhance the dressings antimicrobial properties. The resulting hydrogel presented a high degree of swelling and a good size control of silver nanoparticles. The incorporation of AgNPs was confirmed via Raman spectroscopy and the samples presented no signs of toxicity in vitro as assessed using an elution assay with neutral red uptake as the cytotoxic end point. Membranes were tested in vivo using a full thickness defeat model in rabbits. Postmortem histopathological analysis indicated that the use of the hydrogel membranes that incorporated AgNPs had a stimulatory action on wound healing as evidenced by a high intensity of fibroblasts and neovascularization in the tissue, which promoted a faster healing process when compared to the untreated wounds. We demonstrate the possibility of producing a hydrogel with good size control of AgNPs, which can also be directly sterilized within the formation of this material via gamma irradiation. Furthermore, the mechanism of hydrogel healing, in vivo, with silver nanoparticles was found to have a direct correlation of silver nanoparticles with in vitro cell results.

Mechanical properties of anodic titanium films containing ions of Ca and P submitted to heat and hydrothermal treatment.

Anodic oxidation is a technique widely used to improve the bioactivity of Ti surface. In this study, micro-arc oxidation (MAO) was used to obtain an anodic film incorporating Ca and P ions to evaluate the effect of heat and hydrothermal treatment on the mechanical and in vitro bioactivity properties of these new layers. The MAO process was carried out using (CH3COO)2Ca·H2O and NaH2PO4·2H2O electrolytes under galvanostatic mode (150mA/cm(2)). The thermal treatments were made at 400°C and 600°C in air atmosphere while hydrothermal treatment was made in an alkaline water solution at 130°C. These surfaces presented desired mechanical properties for biomedical applications owing to the rutile and anatase phases in the anodic film that are more crystalline after thermal treatments; which provided an increase in hardness values and lower elastic modulus. The dry sliding wear resistance increased by performing thermal treatments on the surfaces with one condition still maintaining the film after the test. Bioactivity was investigated by immersion in simulated body fluid during 21 days and hydroxyapatite was formed on all samples. Finally, lower values of contact angle were obtained for heat treated samples.

Extraction Method Plays Critical Role in Antibacterial Activity of Propolis-Loaded Hydrogels.

Extracted propolis has been used for a long time as a remedy. However, if the release rate of propolis is not controlled, the efficacy is reduced. To overcome this issue, extracted propolis was added to a cryogel system. Propolis collected from southern Brazil was extracted using different methods and loaded at different concentrations into polyvinyl alcohol (PVA) and polyacrylic acid hydrogels as carrier systems. The material properties were investigated with a focus on the propolis release profiles and the cryogel antibacterial properties against 4 different bacteria, namely: Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and Pseudomonas putida. Swelling studies indicated that the swelling of the hydrogel was inversely related to propolis content. In addition, propolis release studies indicated a decreased release rate with increased propolis loading. PVA and PVA/polyacrylic acid-loaded propolis were effective against all 4 bacteria studied. These results indicate that the efficacy of propolis can be enhanced by incorporation into hydrogel carrier systems and that hydrogels with higher concentrations of propolis can be considered for use as bactericide dressing.

Improved tribo-mechanical behavior of CaP-containing TiO2 layers produced on titanium by shot blasting and micro-arc oxidation.

The combination of shot blasting (SB) and micro-arc oxidation (or anodic oxidation--AO) in titanium surfaces was shown to provide enhanced conditions for cell differentiation and osseointegration than those provided by SB or AO alone. This study associated both methods aiming to attain titania layers on Ti with adequate tribo-mechanical features for bone implants. SB was performed using alumina particles, and titania layers were grown by AO using a CaP-based electrolyte. Mechanical properties and scratch resistance were characterized at nanoscale by instrumented indentation and nanoscratch, and correlated with morphological and microstructural changes (XRD, SEM, EDS, AFM, and profilometry). Analytical methods were employed to correct roughness and substrate effects on the indentation results. CaP-containing TiO2 layers were produced on AO and SB + AO. The latter presented small pore size and inhomogeneous layer thickness and Ca/P ratios, caused by the non-uniform surface straining by SB that affects the oxide growth kinetics in the electrochemical process. Elastic modulus of SB + AO layer (37 GPa) were lower than the AO one (45 GPa); both of them were smaller than bulk Ti (130 GPa) and close to bone values. The hardness profiles of AO and SB + AO were similar to the substrate ones. Because of the improved load bearing capacity and unique layer features, the critical load to remove the SB + AO titania coating in scratch tests was three times as much or higher than in AO. Results indicate improved mechanical biocompatibility and tribological strength of anodic titania layers grown on sand blasted Ti surfaces.

Tribo-mechanical characterization of rough, porous and bioactive Ti anodic layers.

Rough and porous titanium oxide layers, which are important features for improving the osseointegration of Ti implants with bone tissues, are obtained through the technique of anodic oxidation. The thicknesses of such coatings are typically in the order of micrometers, and their mechanical characterization can be assessed by instrumented indentation, provided that the composite nature of the surface is considered. Titania anodic layers were produced on Ti under galvanostatic mode using Ca-P-based electrolytes (a mixture of (CH3COO)2Ca⋅H2O and NaH2PO(4)⋅2H2O), employing current densities (J) of 150 mA/cm2 and 300 mA/cm2. The structure and morphology were characterized by X-ray diffraction (XRD), scanning electron microscopy with electron dispersive X-ray spectroscopy (SEM/EDS), and profilometry, and the chemical features were characterized by X-ray photoelectron spectroscopy (XPS). TiO2 layers presented the crystalline phases rutile and anatase, and incorporation of Ca and P presented as a calcium phosphate compound. The porosity, roughness, and thickness increased with J. Analytical methods were employed to obtain the modified layers' elastic modulus and hardness from instrumented indentation data, deducting the substrate and roughness effects. The elastic moduli were about 40 GPa for both values of J, which are similar to the values for human bones (10-40 GPa). The hardness decreased with indentation load, varying from 5 GPa at the near surface to 1 GPa at the layer-substrate interface. Such hardness behavior is a consequence of the surface brittleness under normal loading. Additional scratch tests using an acute tip indicated that the layer integrity under shear forces was 220 mN (J=150 mA/cm2) and 280 mN (J=300 mA/cm2). TiO2 layers produced with both current densities presented good results for in vitro bioactivity tests using simulated body fluid (SBF) solution, which can be attributed to a combined effect of the microstructure, layer porosity, and hydroxyl radicals in plenty at the near surface.