Gold Nanoparticles Capped with a Novel Titanium(IV)-Containing Polyoxomolybdate Cluster: Selective and Enhanced Bactericidal Effect Against Escherichia coli.

Bacterial infections are a public health threat of increasing concern in medical care systems; hence, the search for novel strategies to lower the use of antibiotics and their harmful effects becomes imperative. Herein, the antimicrobial performance of four polyoxometalate (POM)-stabilized gold nanoparticles (Au@POM) against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as Gram-negative and Gram-positive bacteria models, respectively, is studied. The bactericidal studies performed, both in planktonic and sessile forms, evidence the antimicrobial potential of these hybrid nanostructures with selectivity toward Gram-negative species. In particular, the Au@GeMoTi composite with the novel [Ti2 (HGeMo7 O28 )2 ]10- POM capping ligand exhibits outstanding bactericidal efficiency with a minimum inhibitory concentration of just 3.12 µm for the E. coli strain, thus outperforming the other three Au@POM counterparts. GeMoTi represents the fourth example of a water-soluble TiIV -containing polyoxomolybdate, and among them, the first sandwich-type structure having heteroatoms in high-oxidation state. The evaluation of the bactericidal mechanisms of action points to the cell membrane hyperpolarization, disruption, and subsequent nucleotide leakage and the low cytotoxicity exerted on five different cell lines at antimicrobial doses demonstrates the antibiotic-like character. These studies highlight the successful design and development of a new POM-based nanomaterial able to eradicate Gram-negative bacteria without damaging mammalian cells.

Metallocenyl 7-ACA Conjugates: Antibacterial Activity Studies and Atomic-Resolution X-ray Crystal Structure with CTX-M ß-Lactamase.

The conjugation of organometallic groups to current ß-lactam antibiotics is a field of increasing study due to the ability of certain organometallic groups to enhance the antibiotic potency of these drugs. Herein, we report the antibacterial properties of two metallocenyl (ferrocenyl and ruthenocenyl) 7-aminocephalosporanic acid (7-ACA) antibiotic conjugates. Continuing a trend we found in our previous studies, the ruthenocenyl conjugate showed greater antibacterial activity than its ferrocenyl counterpart. Compared with the previously published 7-aminodesacetoxycephalosporanic acid (7-ADCA) conjugates, the 3-acetyloxymethyl group significantly improved the compounds' activity. Furthermore, the Rc-7-ACA compound was more active against clinical Staphylococcus aureus isolates than the ampicillin reference. Noticeably, neither of the two new compounds showed an undesirable toxic effect in HeLa and L929 cells at the concentrations at which they displayed strong antibacterial effects. The antibacterial activity of the two metallocenyl 7-ACA derivatives was further confirmed by scanning electron microscopy (SEM). SEM micrographs showed that bacteria treated with metallocenyl 7-ACA derivatives feature cell wall damage and morphology changes. Using a CTX-M-14 ß-lactamase competition assay based on nitrocefin hydrolysis, we showed that the Rc-7-ACA bound more favorably to CTX-M-14 than its ferrocenyl counterpart, again confirming the superiority of the ruthenocenyl moiety over the ferrocenyl one in interacting with proteins. We also report a 1.47 Å resolution crystal structure of Rc-7-ACA in complex with the CTX-M-14 E166A mutant, an enzyme sharing a similar active site configuration with penicillin-binding proteins, the molecular target of ß-lactam antibiotics. These results strengthen the case for the antibacterial utility of the Rc and Fc groups.

Isolation of exosomes from whole blood by a new microfluidic device: proof of concept application in the diagnosis and monitoring of pancreatic cancer.

BACKGROUND: Exosomes are endocytic-extracellular vesicles with a diameter around 100 nm that play an essential role on the communication between cells. In fact, they have been proposed as candidates for the diagnosis and the monitoring of different pathologies (such as Parkinson, Alzheimer, diabetes, cardiac damage, infection diseases or cancer). RESULTS: In this study, magnetic nanoparticles (Fe3O4NPs) were successfully functionalized with an exosome-binding antibody (anti-CD9) to mediate the magnetic capture in a microdevice. This was carried out under flow in a 1.6 mm (outer diameter) microchannel whose wall was in contact with a set of NdFeB permanent magnets, giving a high magnetic field across the channel diameter that allowed exosome separation with a high yield. To show the usefulness of the method, the direct capture of exosomes from whole blood of patients with pancreatic cancer (PC) was performed, as a proof of concept. The captured exosomes were then subjected to analysis of CA19-9, a protein often used to monitor PC patients. CONCLUSIONS: Here, we describe a new microfluidic device and the procedure for the isolation of exosomes from whole blood, without any need of previous isolation steps, thereby facilitating translation to the clinic. The results show that, for the cases analyzed, the evaluation of CA19-9 in exosomes was highly sensitive, compared to serum samples.

Exosome origin determines cell targeting and the transfer of therapeutic nanoparticles towards target cells.

BACKGROUND: Exosomes are considered key elements for communication between cells, but very little is known about the mechanisms and selectivity of the transference processes involving exosomes released from different cells. RESULTS: In this study we have investigated the transfer of hollow gold nanoparticles (HGNs) between different cells when these HGNs were loaded within exosomes secreted by human placental mesenchymal stem cells (MSCs). These HGNs were successfully incorporated in the MSCs exosome biogenesis pathway and released as HGNs-loaded exosomes. Time-lapse microscopy and atomic emission spectroscopy allowed us to demonstrate the selective transfer of the secreted exosomes only to the cell type of origin when studying different cell types including cancer, metastatic, stem or immunological cells. CONCLUSIONS: In this study we demonstrate the selectivity of in vitro exosomal transfer between certain cell types and how this phenomenon can be exploited to develop new specific vectors for advanced therapies. Specifically, we show how this preferential uptake can be leveraged to selectively induce cell death by light-induced hyperthermia only in cells of the same type as those producing the corresponding loaded exosomes. We describe how the exosomes are preferentially transferred to some cell types but not to others, thus providing a better understanding to design selective therapies for different diseases.

Evaluation of the Antimicrobial Activity and Cytotoxicity of Different Components of Natural Origin Present in Essential Oils.

Even though essential oils (EOs) have been used for therapeutic purposes, there is now a renewed interest in the antimicrobial properties of phytochemicals and EOs in particular. Their demonstrated low levels of induction of antimicrobial resistance make them interesting for bactericidal applications, though their complex composition makes it necessary to focus on the study of their main components to identify the most effective ones. Herein, the evaluation of the antimicrobial action of different molecules present in EOs against planktonic and biofilm-forming Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria was assessed. The bactericidal mechanisms of the different molecules, as well as their cytocompatibility, were also studied. Carvacrol, cinnamaldehyde, and thymol exhibit the highest in vitro antimicrobial activities against E. coli and S. aureus, with membrane disruption the bactericidal mechanism identified. The addition of those compounds (≥0.5 mg/mL) hampers S. aureus biofilm formation and partially eliminates preformed biofilms. The subcytotoxic values of the tested EO molecules (0.015⁻0.090 mg/mL) are lower than the minimum inhibitory and bactericidal concentrations obtained for bacteria (0.2⁻0.5 mg/mL) but are higher than that obtained for chlorhexidine (0.004 mg/mL), indicating the reduced cytotoxicity of EOs. Therefore, carvacrol, cinnamaldehyde, and thymol are molecules contained in EOs that could be used against E. coli⁻ and S. aureus⁻mediated infections without a potential induction of bactericidal resistance and with lower cell toxicity than the conventional widely used chlorhexidine.

Cymantrenyl-Nucleobases: Synthesis, Anticancer, Antitrypanosomal and Antimicrobial Activity Studies.

The synthesis of four cymantrene-5-fluorouracil derivatives (1-4) and two cymantrene-adenine derivatives (5 and 6) is reported. All of the compounds were characterized by spectroscopic methods and the crystal structure of two derivatives (1 and 6), together with the previously described cymantrene-adenine compound C was determined by X-ray crystallography. While the compounds 1 and 6 crystallized in the triclinic P-1 space group, compound C crystallized in the monoclinic P21/m space group. The newly synthesized compounds 1-6 were tested together with the two previously described cymantrene derivatives B and C for their in vitro antiproliferative activity against seven cancer cell lines (MCF-7, MCF-7/DX, MDA-MB-231, SKOV-3, A549, HepG2m and U-87-MG), five bacterial strains Staphylococcus aureus (methicillin-sensitive, methicillin-resistant and vancomycin-intermediate strains), Staphylococcus epidermidis, and Escherichia coli, including clinical isolates of S. aureus and S. epidermidis, as well as against the protozoan parasite Trypanosoma brucei. The most cytotoxic compounds were derivatives 2 and C for A549 and SKOV-3 cancer cell lines, respectively, with 50% growth inhibition (IC50) values of about 7 µM. The anticancer activity of the cymantrene compounds was determined to be due to their ability to induce oxidative stress and to trigger apoptosis and autophagy in cancer cells. Three derivatives (1, 4 and 5) displayed promising antitrypanosomal activity, with GI50 values in the low micromolar range (3-4 µM). The introduction of the 5-fluorouracil moiety in 1 enhanced the trypanocidal activity when compared to the activity previously reported for the corresponding uracil derivative. The antibacterial activity of cymantrene compounds 1 and C was within the range of 8-64 µg/mL and seemed to be the result of induced cell shrinking.

Antimicrobial Photodynamic Therapy Using Encapsulated Protoporphyrin IX for the Treatment of Bacterial Pathogens.

Herein, we report on the antimicrobial photodynamic effect of polymeric nanoparticles containing the endogenous photosensitizer protoporphyrin IX. Compared to equivalent doses of the free photosensitizer, we demonstrated that the photodynamic antimicrobial efficacy of PLGA (polylactic-co-glycolic acid) nanoparticles containing protoporphyrin IX (PpIX) against pathogenic Staphylococcus aureus (S. aureus) is preserved after encapsulation, while photobleaching is reduced. In addition, compared to equivalent doses of the free porphyrin, we show that a reduction in the cytotoxicity in mammalian cell cultures is observed when encapsulated. Therefore, the encapsulation of protoporphyrin IX reduces its photodegradation, while the released photosensitizer maintains its ability to generate reactive oxygen species upon light irradiation. The polymeric nanoencapsulation promotes aqueous solubility for the hydrophobic PpIX, improves its photostability and reduces the cytotoxicity, while providing an extended release of this endogenous photosensitizer.

PLGA nanoparticle-encapsulated lysostaphin for the treatment of Staphylococcus aureus infections.

Staphylococcus aureus possesses the ability to become pathogenic, leading to severe and life-threatening infections. Its methicillin-resistant variant MRSA has garnered high-priority status due to its increased morbidity and associated mortality. This emphasizes the urgency for novel anti-staphylococcal agents. The bacteriocin lysostaphin stands out for its remarkable bactericidal activity against S. aureus, including MRSA, outperforming conventional antibiotics. However, the clinical application of lysostaphin faces challenges, including enzymatic activity loss under physiological conditions and potential immunogenicity. This study introduces a novel approach by encapsulating lysostaphin within polylactic-co-glycolic acid (PLGA) nanoparticles, a biodegradable copolymer known for its biocompatibility and sustained drug release ability. The study assesses the antimicrobial activity of lysostaphin-loaded PLGA nanoparticles against different S. aureus strains, and we also used GFP-expressing S. aureus for facilitating its traceability in planktonic, biofilm, and intracellular infection models. The results showed the significant reduction in bacteria viability both in planktonic and biofilm states. The in vitro intracellular infection model demonstrated the significantly enhanced efficiency of the developed nanoparticles compared to the treatment with the free bacteriocin. This research presents lysostaphin encapsulation within PLGA nanoparticles and offers promising avenues for enhancing lysostaphin's therapeutic efficacy against S. aureus infections.

Tissue-derived mesenchymal stromal cells used as vehicles for anti-tumor therapy exert different in vivo effects on migration capacity and tumor growth.

BACKGROUND: Mesenchymal stem cells (MSCs) have been promoted as an attractive option to use as cellular delivery vehicles to carry anti-tumor agents, owing to their ability to home into tumor sites and secrete cytokines. Multiple isolated populations have been described as MSCs, but despite extensive in vitro characterization, little is known about their in vivo behavior.The aim of this study was to investigate the efficacy and efficiency of different MSC lineages derived from five different sources (bone marrow, adipose tissue, epithelial endometrium, stroma endometrium, and amniotic membrane), in order to assess their adequacy for cell-based anti-tumor therapies. Our study shows the crucial importance of understanding the interaction between MSCs and tumor cells, and provides both information and a methodological approach, which could be used to develop safer and more accurate targeted therapeutic applications. METHODS: We first measured the in vivo migration capacity and effect on tumor growth of the different MSCs using two imaging techniques: (i) single-photon emission computed tomography combined with computed tomography (SPECT-CT), using the human sodium iodine symporter gene (hNIS) and (ii) magnetic resonance imaging using superparamagnetic iron oxide. We then sought correlations between these parameters and expression of pluripotency-related or migration-related genes. RESULTS: Our results show that migration of human bone marrow-derived MSCs was significantly reduced and slower than that obtained with the other MSCs assayed and also with human induced pluripotent stem cells (hiPSCs). The qPCR data clearly show that MSCs and hiPSCs exert a very different pluripotency pattern, which correlates with the differences observed in their engraftment capacity and with their effects on tumor growth. CONCLUSION: This study reveals differences in MSC recruitment/migration toward the tumor site and the corresponding effects on tumor growth. Three observations stand out: 1) tracking of the stem cell is essential to check the safety and efficacy of cell therapies; 2) the MSC lineage to be used in the cell therapy needs to be carefully chosen to balance efficacy and safety for a particular tumor type; and 3) different pluripotency and mobility patterns can be linked to the engraftment capacity of the MSCs, and should be checked as part of the clinical characterization of the lineage.

New insights in osteoarthritis diagnosis and treatment: Nano-strategies for an improved disease management.

Osteoarthritis (OA) is a common chronic joint pathology that has become a predominant cause of disability worldwide. Even though the origin and evolution of OA rely on different factors that are not yet elucidated nor understood, the development of novel strategies to treat OA has emerged in the last years. Cartilage degradation is the main hallmark of the pathology though alterations in bone and synovial inflammation, among other comorbidities, are also involved during OA progression. From a molecular point of view, a vast amount of signaling pathways are implicated in the progression of the disease, opening up a wide plethora of targets to attenuate or even halt OA. The main purpose of this review is to shed light on the recent strategies published based on nanotechnology for the early diagnosis of the disease as well as the most promising nano-enabling therapeutic approaches validated in preclinical models. To address the clinical issue, the key pathways involved in OA initiation and progression are described as the main potential targets for OA prevention and early treatment. Furthermore, an overview of current therapeutic strategies is depicted. Finally, to solve the drawbacks of current treatments, nanobiomedicine has shown demonstrated benefits when using drug delivery systems compared with the administration of the equivalent doses of the free drugs and the potential of disease-modifying OA drugs when using nanosystems. We anticipate that the development of smart and specific bioresponsive and biocompatible nanosystems will provide a solid and promising basis for effective OA early diagnosis and treatment. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement.

Antibody-Functionalized Polymer Nanoparticles for Targeted Antibiotic Delivery in Models of Pathogenic Bacteria Infecting Human Macrophages.

The efficacy of antibody-functionalized poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs), prepared by nanoprecipitation, carrying rifampicin (RIF) against planktonic, sessile, and intracellular Staphylococcus aureus and Escherichia coli is reported here. A biotinylated anti-S. aureus polyclonal antibody, which binds to structural antigens of the whole bacterium, was functionalized on the surface of RIF-loaded PLGA-based NPs by using the high-affinity avidin-biotin complex. This general strategy allows the binding of commercially available biotinylated antibodies. Coculture models of S. aureus ATCC 25923 and Escherichia coli S17 were used to demonstrate the preferential selectivity of the antibody-functionalized NPs against the Gram-positive bacterium only. At 0.2 µg/mL, complete S. aureus eradication was observed for the antibody-functionalized RIF-loaded NPs, whereas only a 5-log reduction was observed for the nontargeted RIF-loaded NPs. S. aureus is a commensal facultative pathogen having part of its live cycle intracellularly in both phagocytic and nonphagocytic cells. Those intracellular bacterial persisters, named small colony variants, have been postulated as reservoirs of relapsed episodes of infection and consequent treatment failure. At 0.5 µg/mL, the RIF-loaded NPs reduced in 2-log intracellular S. aureus-infecting human macrophages. The ability of those antibody-functionalized nanoparticles to prevent biofilm formation or to reduce the bacterial burden in already-formed mature biofilms is also reported here using S. aureus and E. coli single and cocultured biofilms. In the prevention of S. aureus biofilm formation, the antibody-functionalized NPs exerted a superior inhibition of bacterial growth (up to 2 logs) compared to the nonfunctionalized ones. This study demonstrates the selectivity of the synthesized immunonanoparticles and their antimicrobial efficacy in different scenarios, including planktonic cultures, sessile conditions, and even against intracellular infective pathogens.

Elucidating the mechanisms of action of antibiotic-like ionic gold and biogenic gold nanoparticles against bacteria.

The antimicrobial action of gold depends on different factors including its oxidation state in the intra- and extracellular medium, the redox potential, its ability to produce reactive oxygen species (ROS), the medium components, the properties of the targeted bacteria wall, its penetration in the bacterial cytosol, the cell membrane potential, and its interaction with intracellular components. We demonstrate that different gold species are able to induce bacterial wall damage as a result of their electrostatic interaction with the cell membrane, the promotion of ROS generation, and the consequent DNA damage. In-depth genomic and proteomic studies on Escherichia coli confirmed the superior toxicity of Au (III) vs Au (I) based on the different molecular mechanisms analyzed including oxidative stress, bacterial energetic metabolism, biosynthetic processes, and cell transport. At equivalent bactericidal doses of Au (III) and Au (I) eukaryotic cells were not as affected as bacteria did, maintaining unaffected cell viability, morphology, and focal adhesions; however, increased ROS generation and disruption in the mitochondrial membrane potential were also observed. Herein, we shed light on the antimicrobial mechanisms of ionic and biogenic gold nanoparticles against bacteria. Under selected conditions antibiotic-like ionic gold can exert a strong antimicrobial activity while being harmless to human cells.

Real-time in vivo monitoring of the antimicrobial action of combination therapies in the management of infected topical wounds.

The increasing prevalence of non-healing infected wounds has become a serious concern in the clinical practice, being associated to population aging and to the rising prevalence of several chronic conditions such as diabetes. Herein, the evaluation of the bactericidal and antibiofilm effects of the natural antiseptic terpenes thymol and farnesol standing alone or in combination with the standard care antiseptic chlorhexidine was carried out both in vitro and in vivo. The in vitro combinatorial treatment of chlorhexidine associated with those terpenes against Staphylococcus aureus in its planktonic and sessile forms demonstrated a superior antibacterial activity than that of chlorhexidine alone. Real-time in vivo monitoring of infection progression and antimicrobial treatment outcomes were evaluated using the bioluminescent S. aureus strain Xen36. In vivo studies on infected wound splinting murine models corroborated the superior bactericidal effects of the combinatorial treatments here proposed. Moreover, the encapsulation of thymol in electrospun Eudragit® S100 (i.e., a synthetic anionic copolymer of methacrylic acid and ethyl acrylate)-based wound dressings was also carried out in order to design efficient antimicrobial wound dressings.

The E1a Adenoviral Gene Upregulates the Yamanaka Factors to Induce Partial Cellular Reprogramming.

The induction of pluripotency by enforced expression of different sets of genes in somatic cells has been achieved with reprogramming technologies first described by Yamanaka's group. Methodologies for generating induced pluripotent stem cells are as varied as the combinations of genes used. It has previously been reported that the adenoviral E1a gene can induce the expression of two of the Yamanaka factors (c-Myc and Oct-4) and epigenetic changes. Here, we demonstrate that the E1a-12S over-expression is sufficient to induce pluripotent-like characteristics closely to epiblast stem cells in mouse embryonic fibroblasts through the activation of the pluripotency gene regulatory network. These findings provide not only empirical evidence that the expression of one single factor is sufficient for partial reprogramming but also a potential mechanistic explanation for how viral infection could lead to neoplasia if they are surrounded by the appropriate environment or the right medium, as happens with the tumorogenic niche.

Hybrid thermoresponsive nanoparticles containing drug nanocrystals for NIR-triggered remote release.

The on-demand administration of anaesthetic drugs can be a promising alternative for chronic pain management. To further improve the efficacy of drug delivery vectors, high drug loadings combined with a spatiotemporal control on the release can not only relief the pain according to patient's needs, but also improve the drawbacks of conventional burst release delivery systems. In this study, a hybrid nanomaterial was developed by loading bupivacaine nanocrystals (BNCs) into oligo(ethylene glycol) methyl ether methacrylate (OEGMA)-based thermoresponsive nanogels and coupling them to NIR-absorbing biodegradable copper sulphide nanoparticles (CuS NPs). Those CuS NPs were surface modified with polyelectrolytes using layer-by-layer techniques to be efficiently attached to the surface of nanogels by means of supramolecular interactions. The encapsulation of bupivacaine in the form of nanocrystals allowed to achieve CuS@BNC-nanogels having drug loadings as high as 65.5 wt%. The nanocrystals acted as long-lasting drug reservoirs, leading to an elevated localized drug content, which was useful for their application in prolonged pain relief. The CuS@BNC-nanogels exhibited favorable photothermal transducing properties upon NIR-light irradiation. The photothermal effect granted by the CuS NPs triggered the nano-crystallized drug release to be boosted by the collapse of the thermoresponsive nanogels upon heating. Remote control was achieved for on-demand release at a specific time and place, indicating their potential use as an externally activated triggerable drug-delivery system. Furthermore, cell viability tests and flow cytometry analysis were performed showing satisfactory cytocompatibility in the dose-ranging study having a subcytotoxic concentration of 0.05 mg/mL for CuS@BNC-nanogels. This remotely activated nanoplatform is a promising strategy for long-lasting controlled analgesia and a potential alternative for clinical pain management.

Microfluidic Synthesis of Block Copolymer Micelles: Application as Drug Nanocarriers and as Photothermal Transductors When Loading Pd Nanosheets.

The synthesis of polymeric nanoparticles from a block copolymer based on poly(ethylene glycol) and a polymethacrylate containing the nucleobase analog 2,6-diacylaminopyridine is optimized by microfluidics to obtain homogeneous spherical micelles. Loading and delivery properties are studied using naproxen as a model. The incorporation of a Pd precursor in the polymer organic solution fed into the micromixer allows the preparation of Pd(II) precursor-polymer hybrid systems and the subsequent reduction with CO leads to the in situ synthesis of Pd nanosheets inside of the hydrophobic core of the polymeric micelles. This methodology is highly efficient to yield all polymeric nanoparticles loaded with Pd nanosheets as detected by electron microscopy and energy-dispersive X-ray spectroscopy. The cell viability of these Pd nanosheets-containing polymeric nanoparticles is evaluated using five cell lines, showing a high cytocompatibility at the tested concentrations without detrimental effects in cell membrane and nuclei. Furthermore, the use of these hybrid polymeric nanoparticles as photothermal transductors is evaluated using near infrared as irradiation source as well as its application in photothermal therapy using different cell lines demonstrating a high efficiency in all cell cultures.

Pharmacokinetic control on the release of antimicrobial drugs from pH-responsive electrospun wound dressings.

The acidic pH of healthy skin changes during wound healing due to the exposure of the inner dermal and subcutaneous tissue and due to the potential colonization of pathogenic bacteria. In chronic non-healing wounds, the pH values vary in a wide pH range but the appearance of an alkaline shift is common. After a wound is incurred, neutral pH in the wound bed is characteristic of the activation of the cascade of regenerative and remodeling processes. In order to adjust drug release to the specific pH of the wound, herein, drug-loaded wound dressings having pH-responsiveness containing antiseptics and antibiotics and exerting different release kinetics in order to have a perfect match between the drug release kinetics, and the pH conditions of each wound type, were developed. We have fabricated drug-loaded electrospun nanofibers loaded with the antiseptic chlorhexidine, with the broad-spectrum antibiotic rifampicin, and with the antimicrobial of natural origin thymol, using the pH-dependent methacrylic acid copolymer Eudragit® L100-55, which dissolves at pH > 5.5; those drugs were loaded within Eudragit® S100, which dissolves at pH > 7 and, finally, within the methacrylic ester copolymer Eudragit® RS100 which is pH independent and slowly erodes and releases its contained cargo. The antibacterial action of those advanced wound dressings has been evaluated against methicillin-sensitive S. aureus Newman strain expressing the coral green fluorescent protein (cGFP), as a model of a Gram-positive bacteria, and against E. coli S17 strain as a model of a Gram-negative bacteria. It was demonstrated that those combinational products integrate in one device the required characteristics for a wound dressing with the therapeutic action of a contained active principle and can be selected depending on the wound acidic or alkaline status for its appropriated management.

Anti-Inflammatory and Chondroprotective Effects Induced by Phenolic Compounds from Onion Waste Extracts in ATDC-5 Chondrogenic Cell Line.

Osteoarthritis is a prevalent degenerative condition that is closely related to the destruction and inflammation of cartilage. The high prevalence of this pathology exhorts researchers to search for novel therapeutic approaches. Vegetable-fruit wastes have emerged as a promising origin of anti-inflammatory and antioxidant compounds that, in some cases, may also exert chondroprotective effects. This study aims to decipher the potential of onion waste products in the inhibition of molecular events involved in osteoarthritis. Onion extracts showed a high content of phenolic compounds and antioxidant properties. Cytocompatibility was demonstrated in the chondrogenic cell line ATDC-5, exerting viability percentages higher than 90% and a slight increase in the S phase cycle cell. The induction of inflammation mediated by the lipopolysaccharide and onion extracts' treatment substantially inhibited molecular markers related to inflammation and cartilage degradation, highlighting the promising application of onion extracts in biomedical approaches. The in silico analyses suggested that the results could be attributed to protocatechuic, ellagic, and vanillic acids' greater cell membrane permeability. Our work provides distinctive information about the possible application of waste onion extracts as functional components with anti-inflammatory and chondroprotective characteristics in osteoarthritis.

Valorization of Onion Waste by Obtaining Extracts Rich in Phenolic Compounds and Feasibility of Its Therapeutic Use on Colon Cancer.

In this study, the total phenolic content, the antioxidant and antiproliferative activities of onion waste extracts were characterized. Some phenolic compounds present in the extracts were also identified and quantified by HPLC-DAD. Additionally, an in-silico analysis was performed to identify the phenolic compounds with the highest intestinal absorption and Caco-2 permeability. The onion extract possessed a high amount of phenolic compounds (177 ± 9 mg/g extract) and had an effective antioxidant capacity measured by ABTS, FRAP and DPPH assays. Regarding the antiproliferative activity, the onion extracts produced cell cycle arrest in the S phase with p53 activation, intrinsic apoptosis (mitochondrial membrane potential modification) and caspase 3 activation. Likewise, onion waste increased intracellular ROS with possible NF-kB activation causing a proteasome down regulation. In addition, the extracts protected the intestine against oxidative stress induced by H2O2. According to the in-silico analysis, these results could be related to the higher Caco-2 permeability to protocatechuic acid. Therefore, this study provides new insights regarding the potential use of these types of extract as functional ingredients with antioxidant and antiproliferative properties and as medicinal agents in diseases related to oxidative stress, such as cancer. In addition, its valorization would contribute to the circular economy.

Light activated pulsatile drug delivery for prolonged peripheral nerve block.

Regional anesthesia is widely used in peripheral nerve block and in neuraxial anesthesia to reduce anesthetics systemic side effects and shorten recovery times. However, when applied as a single injection (e.g., peripheral nerve block) it is limited by the duration of its effect. Herein, we develop a thermoresponsive nanogel based on poly(oligoethylene glycol methacrylate) containing the long-lasting anesthetic bupivacaine, which can be externally activated by using near-infrared light due to the photothermal properties of hollow gold nanoparticles embedded in the nanogel which facilitate its phase transition, triggering drug release at a controlled temperature above body temperature. Bupivacaine in vitro release can be repeatedly triggered to achieve a controlled pulsatile release of the drug due to the reversible nature of the thermosensitive nanogel, achieving a spatio-temporal control of the release. In vivo sciatic nerve block demonstrates that whereas the administered dose of free bupivacaine produces sensory block and impaired motor function for 2 h, the equivalent bupivacaine dose included in the developed release system can significantly prolong its neurobehavioral anesthetic effect for over 6 h. This release system can also be reactivated multiple times by subsequent irradiation cycles without observing detrimental toxicity in the infiltrated tissues.