Conxita Solans

Multifunctional polyurethane–urea nanoparticles to target and arrest inflamed vascular environment: A potential tool for cancer therapy and diagnosis

Activation of inflammatory pathways in endothelial cells contributes to tumour growth and progression in multiple human cancers. Cellular adhesion molecules are involved in leukocyte recruitment to the vascular inflammatory environment where it plays a critical role in angiogenesis, suppression of apoptosis, proliferation, invasion and metastasis. We describe here the development of streptavidin-coated polyurethane-urea nanoparticles as multifunctional nanocarriers for fluorescence imaging or targeting of the tumour environment to identify and arrest the vascular network irrigating the tumour tissue. The design of these multifunctional nanoparticles involves incorporating streptavidin to the nanoparticle polymeric matrix. The obtained nanoparticles are spherical and exhibit an average diameter of 70-74 nm. Streptavidin-coated nanoparticles spontaneously bind biotinylated antibodies against VCAM-1 and ICAM-1 which in vitro and in vivo specifically attached to inflamed endothelial cells. Indeed the incorporation of CBO-P11 (a specific inhibitor of the vascular endothelial growth factor proangiogenic and proinflammatory pathway) to these nanoparticles allows a targeted pharmacological effect thereby decreasing the proliferation only in inflamed endothelial cells. The multiple functionalisation strategy described here could be exploited for tumour diagnostics or targeted drug delivery to tumour vasculature with a good safety profile and an attractive array of possibilities for biomedical applications.

Comparison and Functionalization Study of Microemulsion-Prepared Magnetic Iron Oxide Nanoparticles

Magnetic iron oxide nanoparticles (MION) for protein binding and separation were obtained from water-in-oil (w/o) and oil-in-water (o/w) microemulsions. Characterization of the prepared nanoparticles have been performed by TEM, XRD, SQUID magnetometry, and BET. Microemulsion-prepared magnetic iron oxide nanoparticles (ME-MION) with sizes ranging from 2 to 10 nm were obtained. Study on the magnetic properties at 300 K shows a large increase of the magnetization ~35 emu/g for w/o-ME-MION with superparamagnetic behavior and nanoscale dimensions in comparison with o/w-ME-MION (10 emu/g) due to larger particle size and anisotropic property. Moringa oleifera coagulation protein (MOCP) bound w/o- and o/w-ME-MION showed an enhanced performance in terms of coagulation activity. A significant interaction between the magnetic nanoparticles and the protein can be described by changes in fluorescence emission spectra. Adsorbed protein from MOCP is still retaining its functionality even after binding to the nanoparticles, thus implying the extension of this technique for various applications.

PLGA nanoparticles prepared by nano-emulsion templating using low-energy methods as efficient nanocarriers for drug delivery across the blood-brain barrier.

Neurodegenerative diseases have an increased prevalence and incidence nowadays, mainly due to aging of the population. In addition, current treatments lack efficacy, mostly due to the presence of the blood-brain barrier (BBB) that limits the penetration of the drugs to the central nervous system. Therefore, novel drug delivery systems are required. Polymeric nanoparticles have been reported to be appropriate for this purpose. Specifically, the use of poly-(lactic-co-glycolic acid) (PLGA) seems to be advantageous due to its biocompatibility and biodegradability that ensure safe therapies. In this work, a novel approximation to develop loperamide-loaded nanoparticles is presented: their preparation by nano-emulsion templating using a low-energy method (the phase inversion composition, PIC, method). This nano-emulsification approach is a simple and very versatile technology, which allows a precise size control and it can be performed at mild process conditions. Drug-loaded PLGA nanoparticles were obtained using safe components by solvent evaporation of template nano-emulsions. Characterization of PLGA nanoparticles was performed, together with the study of the BBB crossing. The in vivo results of measuring the analgesic effect using the hot-plate test evidenced that the designed PLGA loperamide-loaded nanoparticles are able to efficiently cross the BBB, with high crossing efficiencies when their surface is functionalized with an active targeting moiety (a monoclonal antibody against the transferrin receptor). These results, together with the nanoparticle characterization performed here are expected to provide sufficient evidences to end up to clinical trials in the near future.

Nano-emulsions prepared by the phase inversion composition method: Preparation variables and scale up

The aim of this work is to study, through experimental design, the effect of vessel geometry and scale-up in the properties of nano-emulsions prepared through the phase inversion composition method (PIC). Results show that a proper mixing is crucial for small droplet-sized nano-emulsions, especially when remaining free oil is found together with the key liquid crystal phase formed during the emulsification process. In these cases, mixing must be near the perfect mixed model. Proper geometries must be selected to promote a good mixture. Small addition rates V(ad) and high mixing rates omega promote the necessary mixing level. However, results indicate that, if free oil remains together with liquid crystal formed during emulsification, a too high omega could promote coalescence of oil droplets. When a cubic liquid crystal phase Pm3n is formed instead during emulsification, without free oil, coalescence is not promoted, probably due to the extremely high viscosity. For the system where Pm3n is formed during emulsification, scale-up cannot be done, as it would be expected, maintaining adimensional variables--Reynolds, Re, and adimensional time. A perfect correspondence between scales is observed when the total addition time and the lineal mixing rate are maintained between scales instead. Re, i.e. the ratio between inertial and viscous forces, does not seem adequate to describe the system, as inertial forces are worthless due to the extremely high viscosity.

Formation of polymeric nano-emulsions by a low-energy method and their use for nanoparticle preparation

Formation of polymeric O/W nano-emulsions has been studied in the water/polyoxyethylene 4 sorbitan monolaurate/ethylcellulose solution system by the phase inversion composition (PIC) method. These nano-emulsions were used for the preparation of nanoparticles by solvent evaporation. Composition variables such as O/S ratio or final water content as well as emulsification path have been found to play a key role in the formation of stable, nanometer sized emulsions. Nano-emulsions with a constant water content of 90 wt.% and O/S ratios from 50/50 to 70/30 showed an average droplet size of about 200 nm as assessed by dynamic light scattering. Mean nanoparticle diameters, as determined by transmission electron microscopy image analysis, were of the order of 50 nm and showed a slight increase as well as a broader size distribution at increasing O/S ratios. The findings verify that the low-energy emulsification methods are not only valid for aliphatic and semipolar oils, but also for a highly polar solvent such as ethylacetate containing a preformed polymer.

Studies of the relation between phase behavior and emulsification methods with nanoemulsion formation

The main aim of this work was to study the relationship between the type of phases present during the emulsification process, the order of addition of components and the droplet size of the resulting emulsions. In this study, a pseudoternary water/poly(oxyethylene) nonionic surfactant/decane system was chosen as a model system to form oil-in-water emulsions at 25 °C. The phase behavior of the model system was determined at constant temperature in order to know the equilibrium phases and also those involved in the emulsification process. The low-energy emulsification methods studied were A. Addition of oil to an aqueous surfactant dispersion. B. Addition of water to a surfactant solution in oil. C. Mixing preequilibrated samples of the components.

Highly concentrated (gel) emulsions, versatile reaction media

Abstract Highly concentrated (gel) emulsions are characterised by dispersed phase volume fractions exceeding 0.74, the critical value for the most compact packing of monodispersed undistorted spheres. Their structure consists of polyhedral droplets separated by thin films of continuous phase, a structure resembling gas–liquid foams. Their rheological properties vary from elastic to viscoelastic having a gel appearance. One of the most promising applications is their use as reaction media. The recent advances in the preparation of low-density polymeric materials (solid foams, aerogels) are reviewed and new applications are described. These include the preparation of dual meso/macroporous inorganic oxide materials and the use of gel emulsions as alternative to conventional solvent media in chemical and enzyme-catalysed reactions.

Study of nano-emulsion formation by dilution of microemulsions

The influence of different dilution procedures on the properties of oil-in-water (O/W) nano-emulsions obtained by dilution of oil-in-water (O/W) and water-in-oil (W/O) microemulsions has been studied. The system water/SDS/cosurfactant/dodecane with either hexanol or pentanol as cosurfactant was chosen as model system. The dilution procedures consisted of adding water (or microemulsion) stepwise or at once over a microemulsion (or water). Starting emulsification from O/W microemulsions, nano-emulsions with droplet diameters of 20 nm are obtained, independently on the microemulsion composition and the dilution procedure used. In contrast, starting emulsification from W/O microemulsions, nano-emulsions are only obtained if the emulsification conditions allow reaching the equilibrium in an O/W microemulsion domain during the process. These conditions are achieved by stepwise addition of water over W/O microemulsions with O/S ratios at which a direct microemulsion domain is crossed during emulsification. The nature of the alcohol used as cosurfactant has been found to play a key role on the properties of the nano-emulsions obtained: nano-emulsions in the system using hexanol as cosurfactant are smaller in size, lower in polydispersity, and have a higher stability than those with pentanol.

Formation and stability of nano-emulsions in mixed nonionic surfactant systems

The formation of nano-emulsions has been studied in water/ mixed nonionic surfactant/oil systems using two emulsification methods. In one method, the composition was kept constant and the temperature was changed (phase-inversion temperature, PIT, method), while in the other method, water was added dropwise to a solution of the mixed surfactants in oil at constant temperature (method B). The droplet size and stability were determined as a function of surfactant mixing ratio, W1, at 25 °C. The droplet size of nano-emulsions obtained by the PIT method is practically independent of W1 and falls in the range 60-80 nm. In contrast, the droplet size of nano-emulsions prepared by method B, is highly dependent on W1 and varies between 60 and 300 nm. At W1 values where the PIT or the hydrophile—lipophile balance temperature (Thlb) of the system is close to 25 °C, the droplet sizes of the nano-emulsions are similar for both emulsification methods. There are three equilibrium phases of the latter compositions: an aqueous micellar solution or oil-in-water microemulsion (W m), a lamellar liquid-crystalline phase and an oil phase (O) in addition, these nano-emulsions showed higher kinetic stability than those with lower W 1 values (higher T hlb) and consisting of two liquid phases (W m + O).

Novel preparation methods for highly concentrated water-in-oil emulsions

Abstract Kinetically stable water-in-oil (W/O) high-internal-phase-volume-ratio emulsions with gel-like appearance have been formed in water/hydrogenated non-ionic surfactant/oil systems. Their visual aspect varies from transparent to translucent or white depending on composition variables and temperature. Systematic studies undertaken to characterize these emulsions, referred to as gel emulsions, have revealed that they form above the hydrophilic-lipophilic balance (HLB) temperature of the corresponding ternary system. They consist of two isotropic liquid phases; the dispersed phase is composed of aqueous droplets and the continuous phase is a W/O microemulsion. These emulsions can be prepared by gradual addition of the internal phase to the external phase while stirring, the most common method for preparing highly concentrated emulsions. In the ternary systems water/non-ionic surfactant/hydrocarbon we found two new procedures for preparing gel emulsions. (a) Mixing of the three components, at their final composition, with vigorous stirring, can lead, at the appropriate temperature, to gel emulsion formation. (b) Increasing the temperature of an isotropic phase, the composition of which is that of the final emulsion. These methods of preparation have been rationalized in terms of the evolution of system properties during the process.