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In this article, we present a facile and robust method for the surfactant-free preparation of polynorepinephrine stabilised microcapsules templated from an oil-in-water emulsion. The resulting microcapsule structures are dependent on the concentration of Cu2+ used to catalyse norepinephrine polymerisation. When the concentration of Cu2+ increases, the diameter of the microcapsules and the thickness of the shell increase correspondingly. The mechanical and chemical stability provided by the polynorepinephrine shell are explored using surface pressure measurements and atomic force microscopy, demonstrating that a rigid and robust polynorepinephrine shell is formed. In order to demonstrate potential application of the microcapsules in sustained release, Nile red stained squalane was encapsulated, and pH responsive release was monitored. It was seen that by controlling pH, the release profile could be controlled, with highest release efficacy achieved in alkaline conditions, offering a new pathway for development of encapsulation systems for the delivery of water insoluble actives.
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Nanocompuestos/química , Norepinefrina/química , Antibacterianos/síntesis química , Antibacterianos/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Cápsulas/síntesis química , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Emulsiones/química , Escherichia coli/efectos de los fármacos , Humanos , Hidrogeles/síntesis química , Concentración de Iones de Hidrógeno , Recurrencia Local de Neoplasia/tratamiento farmacológico , Polietilenglicoles/química , Neoplasias Cutáneas , Staphylococcus aureus/efectos de los fármacos , Ingeniería de Tejidos , Cicatrización de HeridasRESUMEN
The efficient penetration of drugs into tumors is a major challenge that remains unmet. Reported herein is a strategy to promote extravasation and enhanced penetration using inertial cavitation initiated by focused ultrasound and cone-shaped gold nanoparticles that entrap gas nanobubbles. The cones are capable of initiating inertial cavitation under pressures and frequencies achievable with existing clinical ultrasound systems and of promoting extravasation and delivery of a model large therapeutic molecule in an in vitro tissue mimicking flow phantom, achieving penetration depths in excess of 2 mm. Ease of functionalization and intrinsic imaging capabilities provide gold with significant advantages as a material for biomedical applications. The cones show neither cytotoxicity in Michigan Cancer Foundation (MCF)-7 cells nor hemolytic activity in human blood at clinically relevant concentrations and are found to be colloidally stable for at least 5 d at 37 °C and several months at 4 °C.
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Sistemas de Liberación de Medicamentos/métodos , Oro , Nanopartículas del Metal , Neoplasias/tratamiento farmacológico , Ondas Ultrasónicas , Oro/química , Oro/farmacología , Humanos , Células MCF-7 , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Neoplasias/metabolismo , Neoplasias/patologíaRESUMEN
Engineered polymer films are of significant importance in the field of biomedicine. Poly(dopamine) (PDA) is becoming more and more a key player in this context. Herein, we deposited mixed films consisting of PDA and poly(L-lysine) (PLL) of different molecular weights. The coatings were characterized by quartz crystal microbalance with dissipation monitoring, atomic force microscopy, and X-ray photoelectron spectroscopy. The protein adsorption to the mixed films was found to decrease with increasing amounts of PLL. PDA/PLL capsules were also successfully assembled. Higher PLL content in the membranes reduced their thickness while the ζ-potential increased. Further, endothelial cell adhesion and proliferation over 96 h were found to be independent of the type of coating. Using PDA/PLL in liposome-containing composite coatings showed that sequential deposition of the layers yielded higher liposome trapping compared to one-step adsorption except for negatively charged liposomes. Association/uptake of fluorescent cargo by adherent endothelial cells was found to be different for PDA and PDA/PLL films. Taken together, our findings illustrate the potential of PDA/PLL mixed films as coatings for biomedical applications.
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Células Endoteliales/química , Indoles/química , Liposomas/química , Lisina/química , Polímeros/química , Adhesión Celular/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Indoles/metabolismo , Liposomas/metabolismo , Lisina/metabolismo , Microscopía de Fuerza Atómica , Espectroscopía de Fotoelectrones , Polímeros/metabolismo , Propiedades de SuperficieRESUMEN
Carbon dots (Cdots) have recently emerged as a novel platform of fluorescent nanomaterials. These carbon nanoparticles have great potential in biomedical applications such as bioimaging as they exhibit excellent photoluminescence properties, chemical inertness and low cytotoxicity in comparison to widely used semiconductor quantum dots. However, it remains a great challenge to prepare highly stable, water-soluble green luminescent Cdots with a high quantum yield. Herein we report a new synthesis route for green luminescent Cdots imbuing these desirable properties and demonstrate their potential in biomedical applications. Oligoethylenimine (OEI)-ß-cyclodextrin (ßCD) Cdots were synthesised using a simple and fast heating method in phosphoric acid. The synthesised Cdots showed strong green fluorescence under UV excitation with a 30% quantum yield and exhibited superior stability over a wide pH range. We further assembled the Cdots into nanocomplexes with hyaluronic acid for potential use as theranostic carriers. After confirming that the Cdot nanocomplexes exhibited negligible cytotoxicity with H1299 lung cancer cells, in vitro bioimaging of the Cdots and nanocomplexes was carried out. Doxorubicin (Dox), an anticancer drug, was also loaded into the nanocomplexes and the cytotoxicity effect of Dox loaded nanocomplexes with H1299 lung cancer cells was evaluated. Thus, this work demonstrates the great potential of the novel OEI-ßCD Cdots in bioimaging and as theranostic carriers.
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Liposomes are important components for biomedical applications. Their unique architecture and versatile nature have made them useful carriers for the delivery of therapeutic cargo. The scope of this minireview is to highlight recent developments of biomimetic liposome-based multicompartmentalized assemblies of polymer thin films and colloidal carriers, and to outline a selection of recent applications of these materials in bionanotechnology.
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Materiales Biomiméticos/síntesis química , Liposomas/química , Membranas Artificiales , Nanoestructuras/química , Nanoestructuras/ultraestructura , Polímeros/química , Coloides/química , Cristalización/métodosRESUMEN
Polymer capsules are an interesting concept considered in nanobiotechnology. Approaches that facilitate their assembly remain sought after. Poly(dopamine) (PDA) has been considered and successfully applied in this context. We recently demonstrated that PDA could be copolymerized with different types of poly(N-isopropylacrylamide) (pNiPAAm) to assemble mixed films on planar substrates. Herein, we transferred this approach onto colloidal substrates and characterized the film thickness depending on the film composition and template particles size. While the membrane of capsules assembled using 5 µm template particles exhibited strong dependency on the film composition, smaller templates led to capsules with similar membrane thickness. We then compared the permeability of different capsules using fluorescently labeled dextran and fluorescein. We found that the permeability of capsules was heavily dependent on the polymer composition and the template particle size. These fundamental findings contribute to the potential of these capsules, assembled in one-step, for biomedical applications.
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Resinas Acrílicas/química , Cápsulas/química , Indoles/química , Polímeros/químicaRESUMEN
Biocatalytic surface coatings are prepared herein for localized synthesis of drugs and their on-demand, site-specific delivery to adhering cells. This novel approach is based on the incorporation of an enzyme into multilayered polymer coatings to accomplish enzyme-prodrug therapy (EPT). The build-up of enzyme-containing multilayered coatings is characterized and correlations are drawn between the multilayer film assembly conditions and the enzymatic activity of the resulting coatings. Therapeutic effect elicited by the substrate mediated EPT (SMEPT) strategy is investigated using a prodrug for an anticancer agent, SN-38. The performance of biocatalytic coatings under flow conditions is investigated and it is demonstrated that EPT allows synthesizing the drugs on-demand, at the time desired and in a controllable amount to suit particular applications. Finally, using cells cultured in sequentially connected flow chambers, it is demonstrated that SMEPT affords a site-specific drug delivery, that is, exerts a higher therapeutic effect in cells adhering directly to the biocatalytic coatings than in the cells cultured "downstream". Taken together, these data illustrate biomedical opportunities made possible by engineering tools of EPT into multilayered polymer coatings and present a novel, highly versatile tool for surface mediated drug delivery.
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Biocatálisis , Técnicas de Cultivo de Célula/métodos , Materiales Biocompatibles Revestidos/farmacología , Preparaciones Farmacéuticas/síntesis química , Polímeros/farmacología , Camptotecina/análogos & derivados , Camptotecina/farmacología , Supervivencia Celular/efectos de los fármacos , Glucuronidasa/metabolismo , Células Hep G2 , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Irinotecán , Perfusión , Profármacos/síntesis química , Tecnicas de Microbalanza del Cristal de CuarzoRESUMEN
Liposomes, spherical vesicles consisting of one or more lipid bilayer membrane(s) encapsulating an aqueous medium, are among the prominent players in the field of nanomedicine. Herein, we highlight the newest, atypical applications of liposomes towards their use in biomedicine. In particular, we put special emphasis on innovative chemical modification of liposomes, the interactions of liposomes with cells under the influence of shear stress, and the utilisation of liposomes as drug deposits in polymeric films and as components in synthetic cell mimics.
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Many biomedical applications benefit from responsive polymer coatings. The properties of poly(dopamine) (PDA) films can be affected by codepositing dopamine (DA) with the temperature-responsive polymer poly(N-isopropylacrylamide) (pNiPAAm). We characterize the film assembly at 24 and 39 °C using DA and aminated or carboxylated pNiPAAm by a quartz crystal microbalance with dissipation monitoring (QCM-D), X-ray photoelectron spectroscopy, UV-vis, ellipsometry, and atomic force microscopy. It was found that pNiPAAm with both types of end groups are incorporated into the films. We then identified a temperature-dependent adsorption behavior of proteins and liposomes to these PDA and pNiPAAm containing coatings by QCM-D and optical microscopy. Finally, a difference in myoblast cell response was found when these cells were allowed to adhere to these coatings. Taken together, these fundamental findings considerably broaden the potential biomedical applications of PDA films due to the added temperature responsiveness.
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Resinas Acrílicas/química , Indoles/química , Liposomas/química , Mioblastos/química , Polímeros/química , Proteínas/química , Temperatura , Animales , Adhesión Celular , Línea Celular , Ratones , Estructura Molecular , Mioblastos/citología , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Mixed one-step poly(dopamine) (PDA)/highly branched poly(N-isopropylacrylamide) (pNiPAAm) coatings have been assembled and characterized by X-ray photoelectron spectroscopy (XPS), UV-vis spectroscopy, atomic force microscopy, and quartz crystal microbalance with dissipation monitoring (QCM-D) depending on the deposition temperature below and above the lower critical solution temperature (LCST) of the pNiPAAm. Mixed films were confirmed. The protein adsorption at 24 °C was found to be reduced with increasing amount of pNiPAAm in the mixed coatings, while there was no difference observed for proteins deposition at 39 °C. Further, the ability of these mixed coatings in comparison to the pure PDA and pNiPAAm films to serve as capping layer for surface-immobilized zwitterionic or positively charged liposomes has been assessed by QCM-D. The adhesion of hepatocytes, macrophages, and myoblast to these liposomes-containing hybrid coatings and the uptake of fluorescent lipids from the surface by the adhering cells depending on the capping layers were compared. The latter aspect was found to be dependent on the used capping layer and the type of liposome as carrier for the fluorescent lipid, with the highest uptake found for positive liposomes and pure pNiPAAm as capping layer. Taken together, the assembled hybrid coatings have the potential to be used as functional coatings toward surface-mediated drug delivery.
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Resinas Acrílicas/química , Indoles/química , Polímeros/química , Adsorción , Animales , Línea Celular , Liposomas/química , Ratones , Microscopía de Fuerza Atómica , Espectroscopía de Fotoelectrones , Proteínas/química , Proteínas/metabolismo , Tecnicas de Microbalanza del Cristal de Cuarzo , Dióxido de Silicio/química , TemperaturaRESUMEN
BACKGROUND: Liposomes have gained immerse attention in the field of drug delivery as carriers of therapeutic molecules. Their modification with a polymer either to make them stealth (e.g. using PEG) and/or more stable (e.g. using poly(dopamine) (PDA)) is a crucial aspect to improve their performance e.g. the blood circulation time. Despite their potential, there are only a few commercialized liposome-based formulations for intravenous drug delivery. Hence, there is still considerable need to address the challenges involved in the design and characterization of liposomal therapeutics. In the latter case, it is of paramount importance to consider the dynamic in vivo environment, e.g. the interstitial fluidic pressure in tumors, blood flow, or bile flow in the liver. METHODS: The PEGylation of PDA films was characterized by quartz crystal microbalance with dissipation monitoring, and the optimized protocol was used to assemble PEGylated PDA coated liposomes (LPDA_PEG). Dynamic light scattering, a plate reader, a flow cytometer and a cytotoxicity assay were used to characterize the liposomes and quantify cellular association/uptake and cell viability in the presence and absence of shear stress after 30min and 4h. The immortalized skeletal mouse myoblast (C2C12) cell line was chosen as model cancer cells, and a hepatic cell line (HepG2) was selected due to their importance in nanosized drug carrier clearance from the system in the liver. RESULTS: The presence of hydrophilic cargo did not affect the PDA assembly process. In the absence of shear stress, there was no difference in cellular uptake/association of both PDA coated liposomes (LPDA) and LPDA_PEG for hepatocytes while myoblasts preferentially internalized/associated with LPDA. In the presence of shear stress, hepatocytes preferentially internalized/associated with LPDA after 30min, while there was only a significant difference for myoblasts after 4h. The cell viability remained unaffected in all cases. CONCLUSIONS: LPDA_PEG are a promising platform towards drug delivery. The nature of cells and fluidic flow are important factors to be considered in their characterization using cell cultures. GENERAL SIGNIFICANCE: These findings will contribute in the better understanding of polymer coated liposomes with cells. The importance of microfluidics in cell culture based characterization is demonstrated, and this will eventually affect the way advanced drug delivery vehicles are designed and characterized prior to animal experiments.
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Indoles/química , Liposomas , Polietilenglicoles/química , Polímeros/química , Estrés Fisiológico , Animales , Línea Celular , Dextranos/química , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/química , Cinética , RatonesRESUMEN
Designing surfaces to deliver therapeutic compounds to adhering cells is of paramount importance for both implantable devices and tissue engineering. We report the assembly of composite films consisting of liposomes as drug deposits in a poly(dopamine) matrix. We monitor the film assembly using a quartz crystal microbalance with dissipation. We assess the response of adhering myoblast cells to these films containing fluorescent lipids in terms of uptake efficiency and cell mean fluorescence using flow cytometry. The viability of adhering myoblast cells, when the hydrophobic cytotoxic compound thiocoraline is entrapped in the lipid membrane, is assessed for different films. Coatings with one or two liposome deposition steps are considered. Further, the effect of the polymer separation layers between the liposome layers is determined. We found that it is possible to use the different nano-engineered composite coatings to impose a corresponding cellular response, e.g., a higher amount of embedded liposomes leads to higher uptake efficiency of the fluorescent lipids and cell mean fluorescence or a higher reduction in the viability of the adhering cells. Assessment of the uptake efficiency and cell mean fluorescence over time reveals a decrease in both parameters over 48 h. Our results demonstrate the ability to affect the cell response depending on the properties of the films, opening up a variety of opportunities for biomedical applications in substrate-mediated drug delivery.
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Air-filled lysozyme microbubbles (LSMBs) were engineered as a support for the immobilization of gold nanoparticles and an enzyme, alkaline phosphatase, in order to develop micro-antimicrobial and biosensing devices. Gold nanoparticles immobilized on LSMBs significantly improved the antimicrobial efficacy of the microbubbles against M. lysodeikticus. The surface functionalization of the microbubbles with gold nanoparticles did not affect their echogenicity when exposed to an ultrasound imaging probe. Alkaline phosphatase was conjugated on the surface of microbubbles without compromising its enzymatic activity. The functionalized microbubbles were used for the detection of paraoxon in aqueous solutions.
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Antibacterianos/química , Técnicas Biosensibles/instrumentación , Sistemas de Liberación de Medicamentos/instrumentación , Muramidasa/química , Nanopartículas/química , Antibacterianos/farmacología , Microburbujas , Micrococcus/efectos de los fármacos , Muramidasa/farmacología , Paraoxon/análisis , Plaguicidas/análisis , Ultrasonido , Contaminantes Químicos del Agua/análisisRESUMEN
Cholesterol is a molecule with many tasks in nature but also a long history in science. This feature article highlights the contribution of this small compound to bionanotechnology. We discuss relevant chemical aspects in this context followed by an overview of its self-assembly capabilities both as a free molecule and when conjugated to a polymer. Further, cholesterol in the context of liposomes is reviewed and its impact ranging from biosensing to drug delivery is outlined. Cholesterol is and will be an indispensable player in bionanotechnology, contributing to the progress of this potent field of research.
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Biotecnología/tendencias , Colesterol/química , Nanoestructuras/química , Nanoestructuras/ultraestructura , Nanotecnología/tendenciasRESUMEN
The sonochemical oil-in-water miniemulsion polymerization of n-butyl methacrylate (BMA) has been studied in mixtures with a range of aliphatic and aromatic hydrocarbon liquids under ambient conditions. Measurements of monomer conversion percentage and molecular weights of the BMA polymers were performed to investigate the effect of the various organic liquids on the kinetics of the polymerization process and on the properties of the resultant polymers. Both the rates of polymerization and the molecular weights of the polymers formed were found to be dependent on the amount and type of the organic liquid present in the emulsion. The experimental results revealed that when the organic liquids were aliphatic, there were no significant changes in the rates of BMA polymerization whereas when the organic liquids were aromatic, the rates of polymerization were greatly reduced. Molecular weight data of the BMA polymers showed that in the presence of an organic liquid, the size of the polymer significantly decreased. The results have been interpreted in terms of the formation of a radical complex between the propagating radical and the organic liquid in the oil mixture, as well as chain transfer reactions that affect the kinetics of the polymerization process.
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Hidrocarburos/química , Polímeros/química , Agua/química , Emulsiones/química , Cinética , Metacrilatos/química , Aceites/química , PolimerizacionRESUMEN
The sonochemical synthesis of nanosized surface-dissymmetrical (Janus) particles is described. The Janus particles were composed of silica and polystyrene, with the polystyrene portion loaded with nanosized magnetite particles. It is shown that the Janus particles can be used to form kinetically stable oil-in-water emulsions that can be spontaneously broken on application of an external magnetic field. The one-pot synthetic process used to prepare the Janus particles has several advantages over other conventional methods of producing such particles.
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Ultrasound was employed to synthesize poly(N-isopropylacrylamide) [poly(NIPAM)] either as aqueous solutions or microgels in the absence of a chemical initiator. Poly(NIPAM) of different microstructures can be readily prepared via ultrasound irradiation by varying the reaction temperature. At a preparation temperature of 20 degrees C, poly(NIPAM) was formed in aqueous solutions, whereas, at a higher preparation temperature (beyond the lower critical solution temperature of approximately 32 degrees C), poly(NIPAM) microgels were formed. In addition, the high shear gradients generated by the acoustic cavitation process aid to control or vary the molecular weights of poly(NIPAM) formed in aqueous solutions. The swelling behavior of poly(NIPAM) at different concentrations of sodium dodecyl sulfate (SDS) was also studied. An increase in the transition temperature and hydrodynamic size of the particles was attributed to SDS binding to the polymer network through hydrophobic interactions. Light scattering data reflected the formation of larger microgels at low cross-linker concentrations. The encapsulation of rhodamine B within the microgels was achieved by sonicating the monomer containing the dye. The subsequent release of the dye was consistent with Fickian diffusion and the diffusion coefficient of the dye was estimated as 4.0 x 10(-12) and 3.6 x 10(-11) m(2) s(-1) at 20 and 40 degrees C, respectively. From the diffusion coefficients, the viscosities of the polymer samples at 20 and 40 degrees C were determined using the Stokes-Einstein equation to be 77 and 10 cP, respectively.
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A simple and efficacious procedure for the synthesis of magnetite nanoparticles has been achieved via a sonochemical miniemulsion polymerization process. The sonochemically synthesized magnetite encapsulated polymer latex particles exhibit excellent colloidal stability and strong magnetic properties, and are of a size that makes them technologically relevant. This novel method may be readily extended to the preparation of multiple combinations of different polymers and encapsulated materials.
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Química/métodos , Óxido Ferrosoférrico/síntesis química , Látex/síntesis química , Nanopartículas/química , Nanotecnología/métodos , Coloides/química , Emulsiones , Óxido Ferrosoférrico/química , Látex/química , Luz , Magnetismo , Microscopía Electrónica de Transmisión , Tamaño de la Partícula , Polímeros/química , Dispersión de Radiación , Temperatura , UltrasonidoRESUMEN
The synthesis of nanosized polymer latex particles using high-frequency ultrasound (213 kHz) has been successfully performed. The effects of surfactant type and concentration of surfactants on the rates of polymerization, latex size, and molecular weights of the polymers produced are presented.
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Látex/química , Nanopartículas/química , Nanotecnología/métodos , Polímeros/síntesis química , Ultrasonido , Emulsiones , Peso Molecular , Tamaño de la Partícula , Polímeros/química , Tensoactivos/químicaRESUMEN
The ultrasound initiated emulsion polymerization of methyl methacrylate (MMA), n-butyl methacrylate (BMA) and 2-ethylhexyl methacrylate (2EHMA) in the presence of sodium dodecylsulfate as a stabiliser produced latex particles in the size range of 70 nm to 110 nm with molecular weights of the order of 2-6 x 10(6) g mol(-1). The experimental data obtained show significant differences in the rates of polymerization of the methacrylate monomers in the order 2EHMA>BMA>MMA. The rate trend is discussed with respect to the physicochemical properties of the monomers. It is suggested from the results obtained that the mechanism involved in sonochemical formation of the latex particles is very similar to that of a conventional miniemulsion polymerization process.