Bioavailability and biodistribution of differently charged polystyrene nanoparticles upon oral exposure in rats
Walczak, A.P. ; Hendriksen, P.J.M. ; Woutersen, R.A. ; Zande, M. van der; Undas, A.K. ; Helsdingen, J.R. ; Berg, J.H.J. van den; Rietjens, I.M.C.M. ; Bouwmeester, H. - \ 2015
Journal of Nanoparticle Research : an Interdisciplinary Forum for Nanoscale Science and Technology 17 (2015). - ISSN 1388-0764 - 13 p.
zinc-oxide nanoparticles - titanium-dioxide nanoparticles - tissue distribution - silver nanoparticles - particle-size - absorption - food - translocation - microspheres - elimination
The likelihood of oral exposure to nanoparticles (NPs) is increasing, and it is necessary to evaluate the oral bioavailability of NPs. In vitro approaches could help reducing animal studies, but validation against in vivo studies is essential. Previously, we assessed the translocation of 50 nm polystyrene NPs of different charges (neutral, positive and negative) using a Caco-2/HT29-MTX in vitro intestinal translocation model. The NPs translocated in a surface charge-dependent manner. The present study aimed to validate this in vitro intestinal model by an in vivo study. For this, rats were orally exposed to a single dose of these polystyrene NPs and the uptake in organs was determined. A negatively charged NP was taken up more than other NPs, with the highest amounts in kidney (37.4 µg/g tissue), heart (52.8 µg/g tissue), stomach wall (98.3 µg/g tissue) and small intestinal wall (94.4 µg/g tissue). This partly confirms our in vitro findings, where the same NPs translocated to the highest extent. The estimated bioavailability of different types of NPs ranged from 0.2 to 1.7 % in vivo, which was much lower than in vitro (1.6–12.3 %). Therefore, the integrated in vitro model cannot be used for a direct prediction of the bioavailability of orally administered NPs. However, the model can be used for prioritizing NPs before further in vivo testing for risk assessment.
Disintegration of protein microbubbles in presence of acid and surfactants: a multi-step process
Rovers, T.A.M. ; Sala, G. ; Linden, E. van der; Meinders, M.B.J. - \ 2015
Soft Matter 11 (2015)32. - ISSN 1744-683X - p. 6403 - 6411.
bovine serum-albumin - microspheres - nanoparticles - fabrication - stability
The stability of protein microbubbles against addition of acid or surfactants was investigated. When these compounds were added, the microbubbles first released the encapsulated air. Subsequently, the protein shell completely disintegrated into nanometer-sized particles. The decrease in the number of intact microbubbles could be well described with the Weibull distribution. This distribution is based on two parameters, which suggests that two phenomena are responsible for the fracture of the microbubble shell. The microbubble shell is first weakened. Subsequently, the weakened protein shell fractures randomly. The probability of fracture turned out to be exponentially proportional to the concentration of acid and surfactant. A higher decay rate and a lower average breaking time were observed at higher acid or surfactant concentrations. For different surfactants, different decay rates were observed. The fact that the microbubble shell was ultimately disintegrated into nanometer-sized particles upon addition of acid or surfactants indicates that the interactions in the shell are non-covalent and most probably hydrophobic. After acid addition, the time at which the complete disintegration of the shell was observed coincided with the time of complete microbubble decay (release of air), while in the case of surfactant addition, there was a significant time gap between complete microbubble decay and complete shell disintegration.
Injectable nanoparticle-loaded hydrogen system for local delivery of sodium alendronate
Posadowska, U. ; Parizek, M. ; Filova, E. ; Wlodarczyk-Biegun, M.K. ; Kamperman, M.M.G. ; Bacakova, L. ; Pamula, E. - \ 2015
International Journal of Pharmaceutics 485 (2015)1. - ISSN 0378-5173 - p. 31 - 40.
drug-delivery - osteoclast formation - controlled-release - bone - gellan - cytotoxicity - formulation - cells - microspheres - therapeutics
Systemic administration of bisphosphonates, e.g. sodium alendronate (Aln) is characterized by extremely low bioavailability and high toxicity. To omit aforementioned drawbacks an injectable system for the intra-bone delivery of Aln based on Aln-loaded nanoparticles (NPs-Aln) suspended in a hydrogel matrix (gellan gum, GG) was developed. Aln was encapsulated in poly(lactide-co-glycolide) (PLGA 85:15) by solid–oil–water emulsification. Drug release tests showed that within 25 days all the encapsulated drug was released from NPs-Aln and the release rate was highest at the beginning and decreased with time. In contrast, by suspending NPs-Aln in a GG matrix, the release rate was significantly lower and more constant in time. The GG–NPs-Aln system was engineered to be easily injectable and was able to reassemble its structure after extrusion as shown by rheological measurements. Invitro studies showed that the GG–NPs-Aln was cytocompatible with MG-63 osteoblast-like cells and it inhibited RANKL-mediated osteoclastic differentiation of RAW 264.7 cells. The injectability, the sustained local delivery of small doses of Aln and the biological activity render the GG–NPs-Aln system promising for the local treatment of osteoporosis and other bone tissue disorders.
Self-consistent field predictions for quenched spherical biocompatible triblock copolymer micelle
Lebouille, J.G.J.L. ; Tuinier, R. ; Vleugels, L.F.W. ; Cohen Stuart, M.A. ; Leermakers, F.A.M. - \ 2013
Soft Matter 9 (2013)31. - ISSN 1744-683X - p. 7515 - 7525.
interacting chain molecules - angle neutron-scattering - aqueous-solution - statistical-theory - block-copolymers - micellization - adsorption - biodegradation - microspheres - degradation
We have used the Scheutjens–Fleer self-consistent field (SF-SCF) method to predict the self-assembly of triblock copolymers with a solvophilic middle block and sufficiently long solvophobic outer blocks. We model copolymers consisting of polyethylene oxide (PEO) as the solvophilic block and poly(lactic-co-glycolic) acid (PLGA) or poly(e-caprolactone) (PCL) as the solvophobic block. These copolymers form structurally quenched spherical micelles provided the solvophilic block is long enough. Predictions are calibrated on experimental data for micelles composed of PCL-PEO-PCL and PLGA-PEO-PLGA triblock copolymers prepared via the nanoprecipitation method. We establish effective interaction parameters that enable us to predict various micelle properties such as the hydrodynamic size, the aggregation number and the loading capacity of the micelles for hydrophobic species that are consistent with experimental findings
Preparation of monodispersed oil-in-water emulsions through semi-metal microfluidic EDGE systems
Maan, A.A. ; Boom, R.M. ; Schroën, C.G.P.H. - \ 2013
Microfluidics and Nanofluidics 14 (2013)5. - ISSN 1613-4982 - p. 775 - 784.
t-shaped microchannel - droplet formation - membrane emulsification - polymer microchannels - channel structure - y-junctions - microspheres - devices - model - array
EDGE (Edge-based Droplet GEneration) emulsification systems with the ability to produce multiple droplets simultaneously from a single nozzle, were used for the preparation of monodispersed oil-in-water emulsions. The devices (with plateau height of 1 µm) were coated with metals (Cu, CuNi and CuNi/Cu) and had different surface roughness and wettability properties. This influenced the emulsification behavior significantly. The large surface roughness of the CuNi/Cu coated system resulted in stronger non-uniform filling of the plateau as compared to the smoother surfaces of Cu and less rough CuNi, and less droplet formation points in the CuNi/Cu coated system relative to the Cu and CuNi systems. The less hydrophilic CuNi surface, however, provided wider pressure stability than the more hydrophilic Cu and CuNi/Cu surface. A narrower pressure stability (Cu surface) and lower number of droplet formation points (CuNi/Cu surface) resulted in lower overall droplet formation frequency when compared with CuNi system. All metal coated EDGE systems reliably produced monodispersed droplets (with sizes being 6 times the plateau height), similar to the silicon-based EDGE systems having much smoother surfaces. The pressure stability for CuNi coated surfaces was wider, while the droplet formation frequency was comparable to that with the silicon system. This indicated that the use of metal is not a limitation in these systems as initially expected, but may be used for more robust and productive emulsification systems, which lend themselves well for scale-out to practical productivity rates.
Colloidosomes: Versatile microcapsules in perspective
Rossier Miranda, F.J. ; Schroën, C.G.P.H. ; Boom, R.M. - \ 2009
Colloids and Surfaces. A: Physicochemical and Engineering Aspects 343 (2009)1-3. - ISSN 0927-7757 - p. 43 - 49.
oil-water interface - emulsion droplet interface - latex-particles - composite tectocapsules - colloidal particles - pickering emulsions - shell structure - capsules - spheres - microspheres
Colloidal particles of different sizes and shapes can organize on suspended particles or emulsion droplets, forming hollow-porous microcapsules called colloidosomes. The potential of the colloidosomes to serve as targeted delivery/controlled release devices has been discussed many times in literature. However, obtaining well-defined colloidosomes at high yields is still an open challenge. We review and compare the different methods reported in literature to produce colloidosomes, not only to show the state of the art and the aspects requiring further development, but also to spot the possible future perspectives of research in this field
Dynamic Interfacial Tension Measurements with Microfluidic Y-Junctions
Steegmans, M.L.J. ; Warmerdam, A. ; Schroën, C.G.P.H. ; Boom, R.M. - \ 2009
Langmuir 25 (2009)17. - ISSN 0743-7463 - p. 9751 - 9758.
membrane emulsification - surfactant adsorption - droplet formation - marangoni flow - microspheres - emulsions - oxide) - model
Emulsification in microdevices (microfluidic emulsification) involves micrometer-sized droplets and fast interface expansion rates. In addition, droplets are formed in less than milliseconds, and therefore traditional tensiometric techniques cannot be used to quantify the actual interfacial tension. In this paper, monodisperse droplets formed at flat microfluidic Y-junctions were used to quantify the apparent dynamic interfacial tension during (microfluidic) emulsification. Hexadecane droplets were formed in ethanol-water solutions with a range of static interfacial tensions to derive a calibration curve, which was subsequently used to access the dynamic interfacial tension of hexadecane droplets formed in surfactant solutions. For SDS and Synperonic PEF108, various continuous- and disperse-phase (hexadecane) flow rates were studied, and these conditions were linked to interfacial tension effects, which also allowed convective transport of surfactants to be investiagted. On the basis of these findings, various strategies for the formation of emulsion droplets can be followed and are discussed
Hollow Polylactide Microcapsules with Controlled Morphology and Thermal and Mechanical Properties
Sawalha, H.I.M. ; Schroën, C.G.P.H. ; Boom, R.M. - \ 2009
AIChE Journal 55 (2009)11. - ISSN 0001-1541 - p. 2827 - 2834.
poly(l-lactic acid) - contrast agent - poly(lactic acid) - drug-release - microspheres - nonsolvent - particles - membranes - films
Hollow polylactide microcapsules were prepared by multistage premix membrane emulsification of polylactide/dichloromethane/oil solutions in water (nonsolvent). The effects of the different oils on the morphology, thermal, and mechanical properties of the hollow microcapsules were investigated. All oils resulted in hollow microcapsules with controlled shell thickness of 60 nm except for eugenol, in which irregular, massive capsules were obtained. The properties of the microcapsules were strongly dependent on the oil used, for example the thermal transition temperatures found for hollow capsules were lower than for solid particles prepared without any oil. The crystallinity and transition temperatures of the capsules prepared with linear alkanes were higher than for cyclic alkanes; terpenes gave the lowest transition temperatures. The shell stiffness, measured with atomic force microscopy, was highly dependent on the oil used. Capsules prepared with dodecane showed higher stiffness (3.3 N m-1) than with limonene (2 N m-1) or cyclohexane (1.4 N m-1)
A Geometric Model for the Dynamics of Microchannel Emulsification
Zwan, E.A. van der; Schroën, C.G.P.H. ; Boom, R.M. - \ 2009
Langmuir 25 (2009)13. - ISSN 0743-7463 - p. 7320 - 7327.
in-water emulsions - droplet formation - array - channel - cfd - microspheres - prediction - diameter - plate
Microchannel emulsification is an interfacial tension driven method to produce monodisperse microdroplets, or microspheres. In this paper we introduce a model for describing the dynamics of microchannel emulsification based on simple time dependent geometric shape analysis. The model is based on mechanistic principles that simultaneously predicts both process and microchannel geometry effects. The model contains no adjustable (fit) parameters and is thus fully predictive for oil in water emulsification. The model is easy to use and does not require extensive computational time and/or memory. The model was validated by comparison with the experimental results published by Sugiura and co-workers and we found excellent agreement. It was found that the droplet size of oil in water emulsions could be fully predicted using only two dimensionless numbers, an adapted capillary number that also comprises effects of terrace width and height, and the ratio of terrace length over terrace height. Based on these findings, a dimensionless design map could be constructed for a wide range of process conditions and microchannel dimensions
Microchannel Emulsification: From Computational Fluid Dynamics to Predictive Analytical Model
Dijke, K.C. van; Schroën, C.G.P.H. ; Boom, R.M. - \ 2008
Langmuir 24 (2008)18. - ISSN 0743-7463 - p. 10107 - 10115.
emulsion droplet formation - t-shaped microchannel - membrane emulsification - flow - cfd - channel - microspheres - simulation - diameter - tension
Emulsion droplet formation was investigated in terrace-based microchannel systems that generate droplets through spontaneous Laplace pressure driven snap-off. The droplet formation mechanism was investigated through high-speed imaging and computational fluid dynamics (CFD) simulation, and we found good agreement in the overall shape of the phases during droplet formation. An analytical model was derived from the insights that were gained from the CFD simulations, which describes the droplet diameter as a function of applied pressure. The analytical model covers the influence of both process parameters and geometry of the terrace well and can be used for fast optimization and evaluation studies.
Preparation of hollow polylactide microcapsules through premix membrane emulsification-Effects of nonsolvent properties
Sawalha, H.I.M. ; Fan Yuxuan, ; Schroën, C.G.P.H. ; Boom, R.M. - \ 2008
Journal of Membrane Science 325 (2008). - ISSN 0376-7388 - p. 665 - 671.
contrast agents - microspheres - drug - size - delivery - release - homogenization - encapsulation - emulsions - ink
Hollow polylactide microcapsules that can be used as ultrasound contrast agents were prepared using premix membrane emulsification. Polylactide/dichloromethane and dodecane solutions were emulsified together with a nonsolvent phase (water or a water¿alcohol mixture) by repeated passage through a glass fibre membrane. The solvent, dichloromethane, diffuses out of the droplets and the polylactide solidifies around a droplet of dodecane. To investigate the effect of the nonsolvent properties on the size and span of the microcapsules, different methanol¿water, ethanol¿water and 2-propanol¿water mixtures were used as nonsolvents. The alcohol lowers the interfacial tension and increases the viscosity of the nonsolvent, and therewith it decreases the size and the span of the microcapsules. It was remarkable that 2-propanol yields the smallest size (0.35 ¿m) followed by ethanol (0.8 ¿m) and methanol (1.4 ¿m). In contrast, the smallest span was obtained with methanol (0.7), whereas 2-propanol gave the largest span (1.5). The results further show that the size and the span of the microcapsules decreases with increasing number of emulsification passes and transmembrane flux. The presence of alcohol in the nonsolvent phase increases the efficiency of the emulsification process and decreases the optimum number of passes required to obtain the minimum average size of the droplets. A three-parameter correlation was defined that could quantitatively describe the effects of all the aforementioned parameters on the size of the microcapsules.
Stabilization of Polymersome Vesicles by an Interpenetrating Polymer Network
Li, F. ; Ketelaar, M.J. ; Marcelis, A.T.M. ; Leermakers, F.A.M. ; Cohen Stuart, M.A. ; Sudhölter, E.J.R. - \ 2007
Macromolecules 40 (2007)2. - ISSN 0024-9297 - p. 329 - 333.
dilute aqueous-solution - diblock copolymers - triblock copolymer - block-copolymers - force microscopy - drug-delivery - nile red - micelles - microspheres - membranes
Vesicles from Pluronic L121 (PEO5-PPO68-PEO5) triblock copolymers were stabilized by an interpenetrating polymer network from pentaerythritol tetraacrylate by UV or thermal initiator induced radical polymerization. Fluorescence labeling, atomic force microscopy, and electron microscopy studies were used to study the morphology of the particles and showed that stable vesicles are formed. The block copolymers are noncovalently trapped in the interpenetrating polyacrylate network. The stabilized vesicles retain their size for more than 1 month at room temperature. Upon cooling, the vesicles reversibly lose block copolymer
Status of cross-flow membrane emulsification and outlook for industrial application
Gijsbertsen-Abrahamse, A.J. ; Padt, A. van der; Boom, R.M. - \ 2004
Journal of Membrane Science 230 (2004)1-2. - ISSN 0376-7388 - p. 149 - 159.
shirasu-porous-glass - in-water emulsions - microchannel emulsification - droplet formation - ceramic membranes - microspheres - size - pore
Cross-flow membrane emulsification has great potential to produce monodisperse emulsions and emulsions with shear sensitive components. However, until now, only low disperse phase fluxes were obtained. A low flux maybe a limiting factor for emulsion production on a commercial scale. Therefore, the effects of membrane parameters on the disperse phase flux are estimated. Besides, the effects of these parameters on the droplet size and droplet size distribution are qualitatively described. Wetting properties, pore size and porosity mainly determine the droplet size (distribution). Membrane morphology largely determines the disperse phase flux. As an example, industrial-scale production of culinary cream was chosen to evaluate the required membrane area of different types of membranes: an SPG membrane, an alpha-Al2O3 membrane and a microsieve. Due to the totally different morphologies of these membranes, the fraction of active pores is I for a microsieve and is very low for the other membranes. The choice of the optimal membrane did not depend on the production strategy: either to produce large quantities or to produce monodisperse emulsions, the best suitable was a microsieve with an area requirement of around I m(2). In general, the total membrane resistance should be low to obtain a large disperse phase flux. In contrast, the membrane resistance should be high to obtain monodisperse emulsions when using membranes with a high porosity. (C) 2003 Elsevier B.V. All rights reserved.