Tuning complement activation and pathway through controlled molecular architecture of dextran chains in nanoparticle corona

International audienceThe understanding of complement activation by nanomaterials is a key to a rational design of safe and efficient nanomedicines. This work proposed a systematic study investigating how molecular design of nanoparticle coronas made of dextran impacts on mechanisms that trigger complement activation. The nanoparticles used for this work consisted of dextran-coated poly(isobutylcyanoacrylate) (PIBCA) nanoparticles have already been thoroughly characterized. Their different capacity to trigger complement activation established on the cleavage of the protein C3 was also already described making these nanoparticles good models to investigate the relation between the molecular feature of their corona and the mechanism by which they triggered complement activation. Results of this new study shows that complement activation pathways can be selected by distinct architectures formed by dextran chains composing the nanoparticle corona. Assumptions that explain the relation between complement activation mechanisms triggered by the nanoparticles and the nanoparticle corona molecular feature were proposed. These results are of interest to better understand how the design of dextran-coated nanomaterials will impact on interactions with the complement system. It can open perspectives with regard to the selection of a preferential complement activation pathway or prevent the nanoparticles to activate the complement system, based on a rational choice of the corona configuration

MICROEMULSÃO: UM PROMISSOR CARREADOR PARA MOLÉCULAS INSOLÚVEIS

Microemulsão (ME) é um sistema que foi descoberto por Hoar e Schulman no ano de 1943 e que é termodinamicamente estável e isotropicamente translúcido de dois líquidos imiscíveis (óleo/água), estabilizados por um filme interfacial de tensoativos. O estudo de sistemas microemulsionados se baseia nas suas três teorias de formação: (1) teoria da solubilização, (2) teoria da tensão interfacial e (3) teoria termodinâmica. A estrutura formada é influenciada pelas propriedades físico-químicas dos componentes utilizados e da razão entre os componentes. O objetivo desta revisão foi avaliar o estado da arte de sistemas microemulsionados enfatizando uma abordagem teórica. Além disso, os recentes avanços sobre a aplicabilidade clínca e utilização como carreador de moléculas insolúveis foram discutidas. Palavras-chave: Aplicações Clínicas. Diagrama de Fases. Microemulsão. ABSTRACT Microemulsion: a promising carrier system for insoluble compounds Microemulsions (ME) are thermodynamically stable and isotropic systems of two immiscible liquids (oil/water), stabilized by an interfacial film of surfactants, discovered by Hoar and Schulman in 1943. The study of ME formation is based on three areas of theory: (1) solubilization, (2) interfacial tension and (3) thermodynamics. ME structures are influenced by the physicochemical properties and proportions of their ingredients. The goal of this review is to assess the state of the art of microemulsified systems, from a theoretical viewpoint. Also, recent progress on their clinical application and use as carriers for insoluble compounds is discussed. Keywords: Microemulsion. Pharmaceutical Application. Phase Diagram

Desenvolvimento de biofilmes à base de xilana e xilana/gelatina para produção de embalagens biodegradáveis

Resumo O objetivo deste trabalho foi desenvolver e caracterizar filmes biodegradáveis à base de xilana extraída de sabugo de milho com potencial uso como uma nova matéria-prima para embalagens biodegradáveis. Para tanto, os filmes foram produzidos através da secagem das dispersões filmogênicas com diferentes concentrações de xilana (150 mg, 300 mg, 600 mg), e glicerol (5%, 10%, 15%), com ou sem adição de gelatina (1000 mg). A caracterização avaliou a morfologia, espessura, solubilidade, biodegradabilidade e opacidade. Os filmes com melhores propriedades foram testados como biocobertura em uvas ‘Itália’ em duas condições de temperatura: ambiente (25 °C) e refrigerada (4 °C). Os parâmetros de perda de massa e acidez objetivaram avaliar sua eficácia. Os resultados mostraram que os filmes a base de xilana/gelatina apresentaram os melhores aspectos macroscópicos. Além disso, o aumento da concentração de xilana fez decrescer sua solubilidade. Conclui-se que a eficácia dos filmes como bioembalagem foi dependente da concentração de xilana na formulação e do período de avaliação

Influence of the Lipophilic External Phase Composition on the Preparation and Characterization of Xylan Microcapsules—A Technical Note

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Producing xylan/Eudragit (R) S100-based microparticles by chemical and physico-mechanical approaches as carriers for 5-aminosalicylic acid

Xylan is a biopolymer found in a variety of cell wall plants. Eudragit (R) S-100 (ES100), a pH-dependent polymer, is used as a coating material in gastroresistant delivery systems. In this study, microparticles based on both polymers were produced by interfacial cross-linking polymerisation and/or spray-drying technique in order to investigate feasibility and stability of the systems. Size and morphology of the microparticles were characterised by optical and SEM while FT-IR, thermal analysis (TG/DTA), and X-ray diffraction (XRD) evaluated the drug-polymer interactions and the thermal behaviour of the systems. FT-IR confirmed the absence of chemical interaction between the polymers. TG/DTA analysis showed a higher stability for spray-dried microparticles and XRD data proved the amorphous feature of both carriers. The results reveal that xylan/ES100 microparticles can be produced by chemical or physico-mechanical ways, the latter being the best option due to the lack of toxic cross-linking agents and easy scale-up.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Development of diethylcarbamazine-loaded poly(caprolactone) nanoparticles for anti-inflammatory purpose: Preparation and characterization

Diethylcarbamazine-loaded nanoparticles were previously evaluated for their anti-inflammatory activity. However, little is known regarding their physicochemical properties. Thus, the purpose of this study was to physiochemically characterize diethylcarbamazine-loaded poly(caprolactone) nanoparticles and evaluate their in vitro cytotoxicity. All formulations were prepared using the double-emulsion method. The average particle size was in the ranged between 298 and 364 nm and the polydispersity indexes were below 0.3. The zeta potential values were marginally negative, which may be related to drug loading, as higher loading led to an increase in the modulus of the zeta potential values. Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XRD) analysis did not reveal any chemical interactions between the chemicals used and the absence of drug in crystalline form on the nanoparticle surfaces. The in vitro drug release study revealed a concentration-dependent release from the nanoparticles into the medium. The in vitro cytotoxicity assay demonstrated the biocompatibility of the blank and loaded nanoparticles. Hence, all formulations presented good physicochemical and safety properties, corroborating the in vivo anti-inflammatory activity, previously reported by our group

Xylan from corn cobs, a promising polymer for drug delivery: Production and characterization

Although many authors have reported several beneficial effects ascribed to xylan, such as inhibitory action on mutagenicity activity. antiphlogistic effects, and mitogenic and comitogenic activities, few papers have investigated a systematic study on the technological properties of this polymer. The aim of the present work was to evaluate xylan as a promise raw material for the pharmaceutical industry. The water-insoluble xylan samples were extracted from corn cobs following several steps. The obtained powered sample was analyzed by infrared and RMN spectroscopy, and characterized regarding their particle size, bulk and tap densities, compressibility index, compactability, Hausner ratio, and angle of repose. According to the results, infrared and RMN spectroscopy were shown to be able to evaluate the xylan structural conformation and composition, respectively. In addition, rheological data demonstrated that xylan powder obtained from corn cobs may be characterized as a material with low density and very cohesive flow properties. (C) 2010 Elsevier Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES