Effects of Organic Solvents on Hyaluronic Acid Nanoparticles Obtained by Precipitation and Chemical Crosslinking

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Hyaluronic acid is a hydrophilic mucopolysaccharide composed of alternating units of D-glucuronic acid and N-acetylglucosamine. It is used in many medical, pharmaceutical, and cosmetic applications, as sponges, films, or particle formulations. Hyaluronic acid nanoparticles can be synthesized free of oil and surfactants by nanoprecipitation in organic solvents, followed by chemical crosslinking. The organic solvent plays an important role in particles size and structure. Therefore, this study aimed to investigate the influence of acetone, ethanol, and isopropyl alcohol on the synthesis and physico-chemical properties of hyaluronic acid nanoparticles. Particles were crosslinked with adipic hydrazide and chloride carbodiimide under controlled conditions. The nanoparticles obtained with all three studied solvents were moderately electrostatically stable. Experiments with acetone produced the smallest particle size (120.44 nm) and polydispersity (0.27). The size and polydispersity of hyaluronic acid nanoparticles correlated with the surface tension between water and the organic solvents, not with the thermodynamic affinity of water for the organic solvents.12328492857Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Production of hyaluronic acid (HA) nanoparticles by a continuous process inside microchannels: Effects of non-solvents, organic phase flow rate, and HA concentration

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Nanostructured materials have drawn increased interest due to their potential applications in various scientific and technological areas. Additionally, interest in natural polymers has grown because of their biodegradability and non-toxicity. Although hyaluronic acid (HA) is an attractive natural polymer capable of hydration and interaction with cells of the immunological system, there have been few studies on the preparation of HA nanoparticles. Nanoparticles have generally been prepared through emulsification or nanoprecipitation in discontinuous processes. In this work, we describe an innovative process for production of HA nanoparticles by nanoprecipitation at the interface of organic solvent/water phases, flowing in laminar flow inside microchannels. The results showed that the production of nanosized HA nanoparticles crosslinked with adipic dihydrazide and chloride carbodiimide was feasible in a cross junction microchannel. This continuous process provided better controlled conditions, which led to more homogeneously sized nanoparticles than the conventional discontinuous processes. The influence of the organic solvent (HA non-solvent), its flow rate, and the HA concentration were studied. The produced nanoparticles presented sizes ranging from 140 to 460 nm, depending on operational conditions, low polydispersity, and negative zeta potential irrespective of the experimental conditions. The smallest particles were obtained with ethanol, due to its higher affinity for water, at the lower HA concentrations or with the higher flow rates of the organic phase. (C) 2012 Elsevier Ltd. All rights reserved.84134141Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES