Opportunities and challenges for antimicrobial nanostructured materials in the management of skin infections

The management of skin and soft-tissue infections represents a burden for healthcare systems worldwide, demanding additional scientific efforts. Despite combined advances in modern medicine from different disciplines, chronic non-healing topical wounds still represent an unresolved clinical challenge. Nanotechnology has contributed significantly to the development of advanced therapeutic and diagnostic approaches in wound care. From this perspective, recommendations on the design of nano-based approaches for the management of infected non-healing chronic wounds are suggested. Preclinical results have demonstrated that nanostructured antimicrobial-loaded dressings and hydrogels can reduce the pathogenic bioburden and can restore the wound’s physiological balance. Future clinical trials that ensure meaningful results are recommended

High Speed Sterilization of Water using Cellulose Grafted Membranes with Metallic Nanoparticles

The removal of bacteria and other organisms from water is an extremely important process, not only for drinking and sanitation but also industrially as bio-fouling is a commonplace and serious problem. This project presents a cellulose membrane filter grafted with silver nanoparticles for the high speed sterilization of water. In order to study the antimicrobial effects of silver nanoparticles, silver nano wires and nano spheres were synthesized , dispersed in water and characterized by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) to reveal their formation and corresponding morphologies, dynamic light scattering (DLS) particle size analyser for particle size distribution, RadWag for concentration and finally Ultraviolet visible (UV-vis) scanning spectrophotoscopy to detect the distinct spectrum of the silver nanoparticles produced. These nanoparticles were then covalently bonded to commercially available cellulose filters, and functionalized by either thiol or amine groups. Followed by characterization by HR(S)-TEM, FE-SEM, energy-dispersive X-ray spectroscopy (EDXS), inductively coupled plasma atomic emission spectroscopy (ICP-AES), Attenuated total reflection Fourier-transform infrared (ATR FT-IR) to reveal that the cellulose membranes were effectively modified by the thiol or amine groups and highly loaded with well dispersed nanoparticles. As well as X-ray photoelectron spectroscopy (XPS) analysis was used showed that the nanoparticles were immobilized in the membrane by a stable covalent bond with the respective functional groups. The resulting cellulose-metal membranes were subjected to mechanical release testing, thus proving their robustness and suppression to release of the nanoparticles from their cellulose backbone. The metal cellulose filters showed high antimicrobial activity in excess of 99.9% growth inhibition against E. coli a member of the total coliform group. Thus we anticipate our filters with their high antibacterial property and durability can be produced in a cost effective manner and if developed is capable of producing affordable, clean and safe drinking water

Microflow nanoprecipitation of positively charged gastroresistant polymer nanoparticles of Eudragit® RS100: A study of fluid dynamics and chemical parameters

The objective of the present work was to produce gastroresistant Eudragit® RS100 nanoparticles by a reproducible synthesis approach that ensured mono-disperse nanoparticles under the size of 100 nm. Batch and micromixing nanoprecipitation approaches were selected to produce the demanded nanoparticles, identifying the critical parameters affecting the synthesis process. To shed some light on the formulation of the targeted nanoparticles, the effects of particle size and homogeneity of fluid dynamics, and physicochemical parameters such as polymer concentration, type of solvent, ratio of solvent to antisolvent, and total flow rate were studied. The physicochemical characteristics of resulting nanoparticles were studied applying dynamic light scattering (DLS) particle size analysis and electron microscopy imaging. Nanoparticles produced using a micromixer demonstrated a narrower and more homogenous distribution than the ones obtained under similar conditions in conventional batch reactors. Besides, fluid dynamics ensured that the best mixing conditions were achieved at the highest flow rate. It was concluded that nucleation and growth events must also be considered to avoid uncontrolled nanoparticle growth and evolution at the collection vial. Further, rifampicin-encapsulated nanoparticles were prepared using both approaches, demonstrating that the micromixing-assisted approach provided an excellent control of the particle size and polydispersity index. Not only the micromixing-assisted nanoprecipitation promoted a remarkable control in the nanoparticle formulation, but also it enhanced drug encapsulation efficiency and loading, as well as productivity. To the best of our knowledge, this was the very first time that drug-loaded Eudragit® RS100 nanoparticles (NPs) were produced in a continuous fashion under 100 nm (16.5 ± 4.3 nm) using microreactor technology. Furthermore, we performed a detailed analysis of the influence of various fluid dynamics and physicochemical parameters on the size and uniformity of the resulting nanoparticles. According to these findings, the proposed methodology can be a useful approach to synthesize a myriad of nanoparticles of alternative polymers

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 longlasting 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. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND licens

Terapia fototérmica mediante un fotosensibilizador intracelular: La Croconaina

El mundo de la nanomedicina aplicada en el tratamiento de cáncer está creciendo muy rápidamente. De hecho, a lo largo de las últimas décadas se han diseñado muchas nanoterapias como alternativa o mejora de las terapias ya existentes contra el cáncer y contra las enfermedades infecciosas principalmente. Una de ellas, la terapia fototérmica, tiene como finalidad el aprovechar el calor emitido por algunos agentes fototérmicos al absorber luz en el infrarrojo cercano (NIR), para poder así destruir células cancerígenas por ablación térmica. Por otro lado, la croconaina es una molécula ya estudiada como agente fotosensibilizante por su dualidad estructural y de absorbancia frente a cambios de pH, presentando una importante absorción en 800 nm cuando se encuentra en medio ácido (pH 5). Esta característica resulta interesante para una terapia fototérmica más segura y efectiva que solo permite la inactivación de las células cuando se encuentra en su interior (ya que algunos compartimentos intracelulares, endosomas, son ácidos) pues el medio extracelular es ligeramente alcalino. En este trabajo se presenta la compleja síntesis de la croconaina incluida en un macrociclo para evitar su posterior agregación y posible quenching de absorbancia. Asimismo, se muestran nuevas encapsulaciones de croconaina que se han llevado a cabo tanto en nanopartículas poliméricas, mediante nanoprecipitación o doble emulsión, como en niosomas. Estas innovadoras encapsulaciones exhiben beneficios frente a los liposomas ya utilizados para encapsular dicha molécula, pues tienen una mayor estabilidad y reducidos costes. También se resalta la dificultad de lograr el comportamiento dual en medio ácido y alcalino de las nanopartículas cargadas de croconaina, debido a la baja difusión del medio en la nanopartícula, impidiendo su cambio de estructura, o bien de la posible baja concentración de molécula encapsulada dentro de las nanopartículas. Todas las síntesis químicas se han caracterizado mediante resonancia magnética nuclear (RMN), y todas las síntesis de nanopartículas se han caracterizado mediante técnicas de visualización ya sea mediante microscopía electrónica de barrido (SEM) o mediante microscopía electrónica de transmisión (TEM). Por otro lado, el comportamiento fototérmico de la croconaina y las nanopartículas se ha evaluado mediante ensayo espectroscópico de absorción UV/VIS y mediante la monitorización de la temperatura al irradiar las muestras con un láser de 808 nm. Finalmente, se ha comprobado la baja citotoxicidad de la molécula en cultivos celulares de monocitos, y su imposible aplicación, a las dosis estudiadas y con las irradiancias usadas, como agente de terapia fototérmica para la ablación de Estafilococos Aureus en infecciones a causa de la alta resistencia térmica de dicha cepa bacteriana

Ordered mesoporous silica monoliths: synthesis, preparation and potential applications

The work carried out was focused on the preparation of rigid porous silica monoliths, in order to investigate applications as controlled drug release matrices. All work was based on the hexagonally-ordered mesoporous SBA-15 materials, and monoliths were obtained by gel-casting procedures. SBA-15 powder was successfully synthesized and characterized using SEM and TEM imaging, nitrogen adsorption and small-angle X-ray diffraction. Synthesis yielded fibrous SBA-15 particles with diameters between 4,5 and 7,5µm and lengths between 75 and 105µm, and highly ordered cylindrical pores arranged in a hexagonal fashion with a diameter between 5,6 and 6,9 nm. Functionalization of SBA-15 powder was carried out using (3-Aminopropyl)triethoxysilane as a functionalizing agent, in order to test functionalization effects on drug release, and to prepare more stable monoliths. Monoliths were prepared using gel-casting procedures; a suspension of polyacrylamide precursors and powder SBA-15 was centrifuged in a glass mold, and polymer hardening and further removal of the polymer template yielded stable monoliths exhibiting a bimodal pore structure confirmed by intrusion characterization. Macroscopic dimensions of the monoliths were 3mm in diameter and approximately 6 mm in length, with macropores around 3 µm and the characteristic mesopores of SBA-15. Monoliths were also functionalized using (3-Aminopropyl)triethoxysilane. Drug loading for drug delivery experiments was carried out by placing as-synthesized and functionalized SBA-15 powders and monoliths in direct contact with a solution of a model antibiotic, namely cefuroxime sodium salt. Functionalized powders yielded the highest loads, followed by unmodified powders, modified monoliths and with as-synthesized monoliths exhibiting the lowest loads. Drug release experiments were focused on release of cefuroxime from as-synthesized and amino-functionalized SBA-15 powders and monoliths. Monoliths exhibit an initial burst release that was attributed to antibiotic loaded in the macroporous reservoirs, while a more controlled release was obtained from the powder counterparts

A bone-on-a-chip collagen hydrogel-based model using pre-differentiated adipose-derived stem cells for personalized bone tissue engineering

Mesenchymal stem cells have contributed to the continuous progress of tissue engineering and regenerative medicine. Adipose-derived stem cells (ADSC) possess many advantages compared to other origins including easy tissue harvesting, self-renewal potential, and fast population doubling time. As multipotent cells, they can differentiate into osteoblastic cell linages. In vitro bone models are needed to carry out an initial safety assessment in the study of novel bone regeneration therapies. We hypothesized that 3D bone-on-a-chip models containing ADSC could closely recreate the physiological bone microenvironment and promote differentiation. They represent an intermedium step between traditional 2D–in vitro and in vivo experiments facilitating the screening of therapeutic molecules while saving resources. Herein, we have differentiated ADSC for 7 and 14 days and used them to fabricate in vitro bone models by embedding the pre-differentiated cells in a 3D collagen matrix placed in a microfluidic chip. Osteogenic markers such as alkaline phosphatase activity, calcium mineralization, changes on cell morphology, and expression of specific proteins (bone sialoprotein 2, dentin matrix acidic phosphoprotein-1, and osteocalcin) were evaluated to determine cell differentiation potential and evolution. This is the first miniaturized 3D-in vitro bone model created from pre-differentiated ADSC embedded in a hydrogel collagen matrix which could be used for personalized bone tissue engineering

Desarrollo de recubrimientos antimicrobianos sobre dispositivos médicos

Se conocen numerosos casos en los que una amplia variedad de dispositivos médicos como catéteres, stents, prótesis, reservorios de acceso venoso, etc, se infectan tras su implantación en el cuerpo del paciente. Esto se debe a que durante este proceso, los microorganismos que habitan de forma habitual en el interior del cuerpo del paciente o en su epidermis o en la del personal médico sin las debidas medidas de prevención o que proceden de otras fuentes como material quirúrgico y equipos o líquidos de infusión contaminados, colonizan el tejido interno alrededor del dispositivo. Esta colonización puede provocar una infección localizada que en muchas ocasiones deriva en problemas más graves como bacteriemia en la que la infección se transloca al torrente sanguíneo, generando así complicaciones más severas que en la mayoría de los casos conllevan a la retirada del dispositivo médico infectado y a la reimplantación de un nuevo dispositivo con el consiguiente perjuicio para el paciente tras el sometimiento a una nueva cirugía y el consecuente elevado coste terapéutico. Como posible solución a este extendido problema, se plantea el desarrollo de una película polimérica que recubra el dispositivo en cuestión y que presente la capacidad de almacenar un antibiótico que será liberado localmente tras la implantación. De esta manera, junto con el tratamiento vía oral que se administra al paciente, se conseguiría reducir o evitar el riesgo de infección del dispositivo y se conseguirá una liberación local del antimicrobiano deseado

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 Replacemen

Encapsulation of iron-saturated lactoferrin for proteolysis protection with preserving iron coordination and sustained release

Lactoferrin (Lf) is a globular glycoprotein found mainly in milk. It has a very high affinity for iron(III) ions, and its fully saturated form is called holoLf. The antimicrobial, antiviral, anticancer, and immunomodulatory properties of Lf have been studied extensively for the past two decades. However, to demonstrate therapeutic benefits, Lf has to be efficiently delivered to the intestinal tract in its structurally intact form. This work aimed to optimize the encapsulation of holoLf in a system based on the versatile Eudragit® RS polymer to protect Lf against the proteolytic environment of the stomach. Microparticles (MPs) with entrapped holoLf were obtained with satisfactory entrapment efficiency (90–95%), high loading capacity (9.7%), and suitable morphology (spherical without cracks or pores). Detailed studies of the Lf release from the MPs under conditions that included simulated gastric or intestinal fluids, prepared according to the 10th edition of the European Pharmacopeia, showed that MPs partially protected holoLf against enzymatic digestion and ionic iron release. The preincubation of MPs loaded with holoLf under conditions simulating the stomach environment resulted in the release of 40% of Lf from the MPs. The protein released was saturated with iron ions at 33%, was structurally intact, and its iron scavenging properties were preserved