Magnetite-sepiolite nanoarchitectonics for improving zein-based bionanocomposite foams.

Magnetic nanoarchitectures have been used to introduce multifunctionality in biopolymeric matrices. Bionanocomposite foams based on the corn protein zein were prepared for the first time using the hydrophobic properties of zein in a sequential treatment consisting of the removal of ethanol-soluble fractions, followed by the water swelling of the remaining phase and a further freeze-drying process. When this protocol is applied to zein pellets, they can be consolidated as porous monoliths. Moreover, it is possible to incorporate diverse types of inorganic nanoparticles in the starting pellet to produce the bionanocomposite foams. In particular, the preparation of superparamagnetic foams has been explored using two approaches: the direct incorporation of magnetite nanoparticles in a ferrofluid by impregnation in the foams, and the application of the foaming process to mixtures of zein with magnetite nanoparticles alone or previously assembled into sepiolite clay fibers. The first methodology leads to the production of inhomogeneous foams, while the use of magnetite nanoparticles and better Fe3O4-sepiolite nanoarchitectured materials as fillers results in more homogeneous materials with improved water stability and mechanical properties, offering superparamagnetic behavior. The resulting multifunctional foams have been tested in adsorption processes using the herbicide 4-chloro-2-methylphenoxyacetic acid as a model pollutant, confirming their potential utility in decontamination applications in open waters as they can be easily recovered from the aqueous medium using a magnet.

A pre-formulation study of tetracaine loaded in optimized nanostructured lipid carriers.

Tetracaine (TTC) is a local anesthetic broadly used for topical and spinal blockade, despite its systemic toxicity. Encapsulation in nanostructured lipid carriers (NLC) may prolong TTC delivery at the site of injection, reducing such toxicity. This work reports the development of NLC loading 4% TTC. Structural properties and encapsulation efficiency (%EE > 63%) guided the selection of three pre-formulations of different lipid composition, through a 23 factorial design of experiments (DOE). DLS and TEM analyses revealed average sizes (193-220 nm), polydispersity (< 0.2), zeta potential |- 21.8 to - 30.1 mV| and spherical shape of the nanoparticles, while FTIR-ATR, NTA, DSC, XRD and SANS provided details on their structure and physicochemical stability over time. Interestingly, one optimized pre-formulation (CP-TRANS/TTC) showed phase-separation after 4 months, as predicted by Raman imaging that detected lack of miscibility between its solid (cetyl palmitate) and liquid (Transcutol) lipids. SANS analyses identified lamellar arrangements inside such nanoparticles, the thickness of the lamellae been decreased by TTC. As a result of this combined approach (DOE and biophysical techniques) two optimized pre-formulations were rationally selected, both with great potential as drug delivery systems, extending the release of the anesthetic (> 48 h) and reducing TTC cytotoxicity against Balb/c 3T3 cells.

Preparation, characterization and in vitro anticancer performance of nanoconjugate based on carbon quantum dots and 5-Fluorouracil.

This study is focused on the development of a nanodevice for loading and release of 5-Fluorouracil (5-FU) with a view to improving its therapeutic efficiency, using as strategy the fabrication of a nanoconjugate through drug anchorage on the surface of carbon quantum dots (CQD). Several physicochemical and analytical techniques were employed to obtain information about materials morphology, structure, and optical properties. The results indicated that the interactions between both entities resulted in good physicochemical properties and photostability. Acid pH favored drug release, indicating a tendency to release 5-FU from 5-FU-CQD into the tumor microenvironment. The cytotoxicity of CQD and 5-FU-CQD nanoconjugate was evaluated against normal human lung fibroblast (GM07492A) and human breast cancer (MCF-7) cell lines. The CQD was non-toxic, indicating that these materials are biocompatible and can be used as a nanocarrier for 5-FU in biological systems. For the 5-FU-CQD nanoconjugate, it was observed a reduction in toxicity for normal cells compared to free 5-FU, suggesting that drug anchoring in CQD reduced drug-associated toxicity, while for cancer cells exhibited an antitumor effect equivalent to that of the free drug, opening perspectives for the application of this material in anticancer therapy.

Combination of synthetic anthelmintics and monoterpenes: Assessment of efficacy, and ultrastructural and biophysical properties of Haemonchus contortus using atomic force microscopy.

The resistance of Haemonchus contortus to synthetic anthelmintics is of increasing concern; and different strategies are being evaluated to improve parasite control. The present study investigated the in vitro effects of combinations of synthetic compounds and monoterpenes. Additionally, the chemical association of the best combinations and their impact on the ultrastructural and biophysical properties of H. contortus eggs was evaluated. We assessed the efficacy of the monoterpenes, carvacrol, thymol, r-carvone, s-carvone, citral, and p-cymene and the anthelmintics, albendazole and levamisole using the egg hatch test (EHT) and the larval migration inhibition test (LMIT), respectively. The minimum effective concentrations of the monoterpenes, according to the EHT (efficacy ranging from 4.4%-11.8%) and LMIT (efficacy ranging from 5.6%-7.4%), were used in combination with different concentrations of synthetic compounds, and the IC50 and synergism rate (SR) were calculated. Fourier-transform infrared spectroscopy (FTIR) was used to analyze the chemical association between the best combinations as revealed by the in vitro tests (albendazole and levamisole with r-carvone or s-carvone). Atomic force microscopy (AFM) was used to assess the ultrastructural and biophysical properties of H. contortus eggs treated with the albendazole and r-carvone combination. Among the monoterpenes, the highest efficacies were exhibited by carvacrol (IC50 = 185.9 µg/mL) and thymol (IC50 = 187.0 µg/mL), according to the EHT, and s-carvone and carvacrol (IC50 = 1526.0 and 1785.3 µg/mL, respectively), according to the LMIT. According to the EHT, albendazole showed a slight statistically significant synergism in combination with r-carvone (SR = 3.8) and s-carvone (SR = 3.0). According to the LMIT, among the monoterpenes, r-carvone (SR = 1.7) and s-carvone (SR = 1.7) showed an increase in efficacy with levamisole; however, this was not statistically significant. The FTIR spectra of albendazole and levamisole, in association with r-carvone and s-carvone, indicated the presence of chemical interactions between the synthetic and natural molecules, contributing to the possible synergistic effects of these associations. Eggs treated with albendazole and r-carvone showed an increase in roughness and a decrease in height, suggesting that the treatment induced damage to the egg surface and an overflow of its internal contents. Overall, the combination of albendazole with r-carvone and s-carvone was efficacious against H. contortus, demonstrating a chemical association between the compounds; the significant changes in the egg ultrastructure justify this efficacy.

Au@Ag bimetallic nanoparticles deposited on palygorskite in the presence of TiO2 for enhanced photodegradation activity through synergistic effect.

Herbicides are hazardous organic pollutants that contribute to the risk of environmental contamination. The aim of this work was to investigate the synergistic effect of silver (Ag) and gold (Au) bimetallic nanoparticles deposited on palygorskite (PAL) in the presence of TiO2 for photodegradation of bentazone (BTZ) herbicide under UV light. Ag and Au@Ag nanoparticles exhibited an average size below 75 nm and surface charge values less than - 30 mV. UV-Vis spectroscopy indicates the formation of core@shell bimetallic nanoparticles. XRD results showed the interactions between the NPs and the palygorskite structure. SEM images clearly illustrate the presence of small spherical particles distributed in the clay fibers. The control of the size and distribution of the nanoparticles played an important role in the properties of the composites. The degradation of the herbicide BTZ showed that nanoparticles, clay, and only TiO2 did not produce satisfactory results; however, when Ag-Pal and Au@Ag-Pal were in the presence of the TiO2, the degradation was efficient. The best photodegradative system was Au@Ag-Pal+TiO2, which was maintained after the third cycle. The bentazone photodegradation using Au@Ag-PAL+TiO2 exhibited toxicity against Artemia salina. Therefore, Au@Ag-PAL+TiO2 photocatalyst showed that the synergy of bimetallic nanoparticles deposited on clay for enhanced photodegradation activity of bentazone herbicide.

Hybrid nanofilms as topical anesthetics for pain-free procedures in dentistry.

Topical anesthetics are widely applied in order to relieve the discomfort and anxiety caused by needle insertion and other painful superficial interventions at the oral cavity. So far, there are no commercially available effective topical anesthetic formulations for that purpose, and the most of developments are related to hydrophilic and low mucoadhesive forms. Therefore, we have prepared different hybrid nanofilms composed of biopolymer matrices (chitosan, pectin, and chitosan-pectin) blended with nanostructured lipid carriers (NLC) loading the eutectic mixture of 5% lidocaine-prilocaine (LDC-PLC), in order to fulfill this gap in the market. These dual systems were processed as hybrid nanofilms by the solvent/casting method, and its mucoadhesive, structural and mechanical properties were detailed. The most appropriate hybrid nanofilm combined the advantages of both pectin (PCT) and NLC components. The resultant material presented sustained LDC-PLC release profile for more than 8 h; permeation across porcine buccal mucosa almost twice higher than control and non-cytotoxicity against 3T3 and HACAT cell lines. Then, the in vivo efficacy of PCT/NLC formulation was compared to biopolymer film and commercial drug, exhibiting the longest-lasting anesthetic effect (> 7 h), assessed by tail flick test in mice. These pectin-based hybrid nanofilms open perspectives for clinical trials and applications beyond Dentistry.

Zein-layered hydroxide biohybrids: strategies of synthesis and characterization.

This work constitutes a basic study about the first exploration on the preparation of biohybrids based on the corn protein zein and layered metal hydroxides, such as layered double hydroxides (LDH) and layered single hydroxides (LSHs). For this purpose, MgAl layered double hydroxide and the Co2(OH)3 layered single hydroxide were selected as hosts, and various synthetic approaches were explored to achieve the formation of the zein-layered hydroxide biohybrids, profiting from the presence of negatively charged groups in zein in basic medium. Zein-based layered hydroxide biohybrids were characterized by diverse physicochemical techniques such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis/differential thermal analysis (TG/DTA), solid state 13C cross-polarization magical angle spinning nuclear magnetic resonance (CP-MAS NMR), field emission-scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), etc., which suggest that the different synthesis procedures employed and the anion located in the interlayer region of the inorganic host material seem to have a strong influence on the final features of the biohybrids, resulting in mixed, single intercalated, or highly exfoliated intercalated phases. Thus, the resulting biohybrids based on zein and layered hydroxides could have interest in applications in biomedicine, biosensing, materials for electronic devices, catalysis, and photocatalysis.

Improved efficacy of naproxen-loaded NLC for temporomandibular joint administration.

Inflammatory conditions of the temporomandibular joint (TMJ) and peripheral tissues affect many people around the world and are commonly treated with non-steroidal anti-inflammatory drugs (NSAIDs). However, in order to get desirable results, treatments with NSAIDs may take weeks, causing undesirable side effects and requiring repeated administration. In this sense, this work describes the development of an optimized nanostructured lipid carrier (NLC) formulation for intra-articular administration of naproxen (NPX). An experimental design (23) selected the best formulation in terms of its physicochemical and structural properties, elucidated by different methods (DLS, NTA, TEM, DSC, and ATR-FTIR). The chosen formulation (NLC-NPX) was tested on acute inflammatory TMJ nociception, in a rat model. The optimized excipients composition provided higher NPX encapsulation efficiency (99.8%) and the nanoparticles were found stable during 1 year of storage at 25 °C. In vivo results demonstrated that the sustained delivery of NPX directly in the TMJ significantly reduced leukocytes migration and levels of pro-inflammatory cytokines (IL-1ß and TNF-α), for more than a week. These results point out the NLC-NPX formulation as a promising candidate for the safe treatment of inflammatory pain conditions of TMJ or other joints.

Building Up Functional Bionanocomposites from the Assembly of Clays and Biopolymers.

Functional bionanocomposites are developed from the assembly of naturally occurring polymers and inorganic solids that show at least one dimension at the nanoscale. Our research group focused on the development of bionanocomposites based on clay minerals, including smectites and fibrous silicates, as well as layered double hydroxides. The resulting materials show interesting properties regarding biocompatibility and biodegradability, together with improved mechanical and thermal properties in comparison to the pristine biopolymer. Besides these characteristics, they offer also other interesting functional properties that allow their potential use in a wide range of applications, including sensors, drug delivery and other health care applications, bioplastics and environmental remediation. For these materials, nature provides not only the components but also the inspiration to develop new combinations that may give rise to nanostructured biomaterials with exceptional features.

Functional Carboxymethylcellulose/Zein Bionanocomposite Films Based on Neomycin Supported on Sepiolite or Montmorillonite Clays.

The present work introduces new functional bionanocomposite materials based on layered montmorillonite and fibrous sepiolite clays and two biopolymers (carboxymethylcellulose polysaccharide and zein protein) to produce drug-loaded bionanocomposite films for antibiotic topical delivery. Neomycin, an antibiotic indicated for wound infections, was employed as the model drug in this study. The physical properties and the antimicrobial activity of these materials were evaluated as a function of the type of hybrid and the amount of zein protein incorporated in the bionanocomposite films. In addition, the interfacial and physicochemical properties of these new clay-drug hybrids have been studied through a combination of experimental and computational methodologies, where the computational studies confirm the intercalation of neomycin into the montmorillonite layers and the possible penetration of the drug in the tunnels of sepiolite, as pointed out by N2 adsorption and X-ray diffraction techniques. The antimicrobial activity of these bionanocomposite materials show that the films based on montmorillonite-neomycin display a more pronounced inhibitory effect of the bacterial growth than those prepared with the sepiolite-neomycin hybrid. Such effect can be related to the difficult release of neomycin adsorbed on sepiolite due to a strong interaction between both components.

Bionanocomposite systems based on montmorillonite and biopolymers for the controlled release of olanzapine.

Olanzapine (OLZ) is a drug that is used in the treatment of schizophrenia and other psychoses, and it belongs to the thienobenzodiazepine class. The OLZ molecule has low solubility decreasing bioavailability, but has high permeability in membrane biological being classified as a Class II drug substance according to the Biopharmaceutics Classification System. It was reported many side effects of administering OLZ orally. So, in order to increase the bioavailability of drug and possibly reducing some of side effects, this paper proposes a new material able to controllably release the drug in the body. To control the dissolution rate, this work proposes a system that incorporates the drug into montmorillonite (MMT) dispersed in a mixture of alginate (ALG) and xanthan gum (XG) biopolymers. The proposed hybrids and bionanocomposites were characterized by several physicochemical techniques, including XRD, IR-ATR, TG DTA, SEM-EDS and HPLC. The characterization data confirmed the intercalation of the OLZ into the MMT by the ion exchange process, as well as the interaction of the MMT-OLZ with the biopolymers. The release test, conducted under various pH conditions, showed that the proposed system exhibited a more controlled drug release than commercial tablets, indicating that the ALG-XG/MMT-OLZ bionanocomposite can act as a controlled release system for OLZ.

Nanostructured lipid carriers as robust systems for topical lidocaine-prilocaine release in dentistry.

In dental practice, local anesthesia causes pain, fear, and stress, and is frequently the reason that patients abandon treatment. Topical anesthetics are applied in order to minimize the discomfort caused by needle insertion and injection, and to reduce the symptoms of superficial trauma at the oral mucosa, but there are still no efficient commercially available formulations. Factorial design is a multivariate data analysis procedure that can be used to optimize the manufacturing processes of lipid nanocarriers, providing valuable information and minimizing development time. This work describes the use of factorial design to optimize a process for the preparation of nanostructured lipid carriers (NLC) based on cetyl palmitate and capric/caprylic triglycerides as structural lipids and Pluronic 68 as the colloidal stabilizer, for delivery of the local anesthetics lidocaine and prilocaine (both at 2.5%). The factors selected were the excipient concentrations, and three different responses were followed: particle size, polydispersity index and zeta potential. The encapsulation efficiency of the most effective formulations (NLC 2, 4, and 6) was evaluated by the ultrafiltration/centrifugation method. The formulations that showed the highest levels of encapsulation were tested using in vitro release kinetics experiments with Franz diffusion cells. The NLC6 formulation exhibited the best sustained release profile, with 59% LDC and 66% PLC released after 20h. This formulation was then characterized using different techniques (IR-ATR, DSC, DRX, TEM, and NTA) to obtain information about its molecular organization and its physicochemical stability, followed during 14months of storage at 25°C. This thorough pre-formulation study represents an important advance towards the development of an efficient pre-anesthetic for use in dentistry.

Effective intercalation of zein into Na-montmorillonite: role of the protein components and use of the developed biointerfaces.

Biohybrid materials based on the intercalation of zein, the major storage protein in corn, into sodium-exchanged montmorillonite were prepared following two synthesis strategies. The first one made use of zein dissolved in 80% (v/v) ethanol/water solution, the usual solvent for this protein, while the second method is new and uses a sequential process that implies the previous separation of zein components in absolute ethanol. This treatment of zein with ethanol renders a soluble yellow phase and an agglomerate of insoluble components, which are able to intercalate the layered silicate when an aqueous dispersion of montmorillonite is added to the ethanol medium containing both phases. The diverse steps in this second route were investigated individually in order to understand the underlying mechanism that drives to the intercalation of this complex hydrophobic biomacromolecule into the hydrophilic interlayer space of sodium-exchanged montmorillonite. In addition to physicochemical characterization of the resulting materials, these biohybrid interfaces were also evaluated as biofillers in the preparation of diverse ecofriendly nanocomposites.

Bionanocomposites containing magnetic graphite as potential systems for drug delivery.

New magnetic bio-hybrid matrices for potential application in drug delivery are developed from the assembly of the biopolymer alginate and magnetic graphite nanoparticles. Ibuprofen (IBU) intercalated in a Mg-Al layered double hydroxide (LDH) was chosen as a model drug delivery system (DDS) to be incorporated as third component of the magnetic bionanocomposite DDS. For comparative purposes DDS based on the incorporation of pure IBU in the magnetic bio-hybrid matrices were also studied. All the resulting magnetic bionanocomposites were processed as beads and films and characterized by different techniques with the aim to elucidate the role of the magnetic graphite on the systems, as well as that of the inorganic brucite-like layers in the drug-loaded LDH. In this way, the influence of both inorganic components on the mechanical properties, the water uptake ability, and the kinetics of the drug release from these magnetic systems were determined. In addition, the possibility of modulating the levels of IBU release by stimulating the bionanocomposites with an external magnetic field was also evaluated in in vitro assays.

Pectin-coated chitosan-LDH bionanocomposite beads as potential systems for colon-targeted drug delivery.

This work introduces results on a new drug delivery system (DDS) based on the use of chitosan/layered double hydroxide (LDH) biohybrid beads coated with pectin for controlled release in the treatment of colon diseases. Thus, the 5-aminosalicylic acid (5ASA), the most used non-steroid-anti-inflammatory drug (NSAID) in the treatment of ulcerative colitis and Crohn's disease, was chosen as model drug aiming to a controlled and selective delivery in the colon. The pure 5ASA drug and the hybrid material prepared by intercalation in a layered double hydroxide of Mg2Al using the co-precipitation method, were incorporated in a chitosan matrix in order to profit from its mucoadhesiveness. These compounds processed as beads were further treated with the polysaccharide pectin to create a protective coating that ensures the stability of both chitosan and layered double hydroxide at the acid pH of the gastric fluid. The resulting composite beads presenting the pectin coating are stable to water swelling and procure a controlled release of the drug along their passage through the simulated gastrointestinal tract in in vitro experiments, due to their resistance to pH changes. Based on these results, the pectin@chitosan/LDH-5ASA bionanocomposite beads could be proposed as promising candidates for the colon-targeted delivery of 5ASA, with the aim of acting only in the focus of the disease and minimizing side effects.