Beatrice Cattoz

University of Greenwich, Londinium, England, United Kingdom

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Publications (16)62.96 Total impact

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    ABSTRACT: Drug delivery via the eye, nose, gastrointestinal tract and lung are of great interest as they represent patient-compliant and facile methods to administer drugs. However, for a drug to reach the systemic circulation it must penetrate the "mucus barrier". An understanding of the characteristics of the mucus barrier is therefore important in the design of mucus penetrating drug delivery vehicles e.g. nanoparticles. Here, a range of nanoparticles - silica, aluminium coated silica, poly (lactic-co-glycolic acid) (PLGA) and PEGylated PLGA - each with known but different physicochemical characteristics were examined in the presence of mucin to identify those characteristics that engender nanoparticle/mucin interactions and thus, to define "design rules" for mucus penetrating (nano) particles (MPP), at least in terms of the surface characteristics of charge & hydrophilicity. Dynamic light scattering (DLS) and rheology have been used to assess the interaction between such nanoparticles and mucin. It was found that negatively charged and hydrophilic nanoparticles do not exhibit an interaction with mucin whereas positively charged and hydrophobic nanoparticles show a strong interaction. Surface grafted poly (ethylene glycol) (PEG) chains significantly reduced this interaction. This study clearly demonstrates that the established colloid science techniques of DLS and rheology are very powerful screening tools to probe nanoparticle/mucin interactions. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 05/2015; DOI:10.1016/j.ejpb.2015.05.004 · 3.38 Impact Factor
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    ABSTRACT: The interaction of amphiphilic block copolymers of the poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) group with small molecule surfactants may be "tuned" by the presence of selected alcohols, with strong interactions leading to substantial changes in (mixed) micelle morphology, whilst weaker interactions lead to coexisting micelle types. The nature and the strength of the interactions between Pluronic P123 (EO20PO70EO20) and small molecule surfactants (anionic sodium dodecylsulfate, SDS, C12SO4Na), (cationic dodecyltrimethylammonium bromide, C12TAB) and (non-ionic polyoxyethylene(23)lauryl ether, Brij 35, C12EO23OH) is expected to depend on the partitioning of the short, medium and long chain alcohols (ethanol, hexanol and decanol respectively) and was probed using tensiometry, pulsed-gradient spin-echo nuclear magnetic resonance (PGSE-NMR) and small-angle neutron scattering (SANS). The SANS data for aqueous P123 solutions with added alcohols were well described by a charged spherical core/shell model for the micelle morphology. The addition of the surfactants led to significantly smaller, oblate elliptical mixed micelles in the absence of alcohols. Addition of ethanol to these systems led to a decrease in the micelle size, whereas larger micelles were observed upon addition of the longer chain alcohols. NMR studies provided complementary estimates of the micelle composition, and the partitioning of the various components into the micelle. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of Colloid and Interface Science 05/2015; 454. DOI:10.1016/j.jcis.2015.04.068 · 3.37 Impact Factor
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    ABSTRACT: The structures of polymer brushes under confinement were measured using a combination of neutron reflectivity and a surface force type apparatus. The samples were either poly(ethylene oxide), PEO, used to investigate the effect of the grafting density or poly(acrylic acid), PAA, used to determine the effect of charge on the structure of a polymer brushes under confinement. Without confinement both PEO and PAA brushes are found to be highly swollen with water, >50% v/v, with the expected parabolic brush structure. Compression of the PEO brushes with as little as 0.5 bar of confinement is found experimentally to reduce the brush to a polymer block of uniform density that is significantly dehydrated, <12% v/v. Further subsequent increases in the confinement pressure only marginally decrease the hydration and thickness of the polymer block. The grafting density of the brush does not significantly influence this behavior. PAA polymer brushes with little (pH 3) or an intermediate level of charging (pH 5.5) are also found to be compressed into a single uniform density polymer block with a confinement of 5 bar. However, with a high level of charge (pH 9) the brush structure is believed to be partially retained due to the repulsion between the internal charges. These experimental results are compared against a theoretical model based on numerical self-consistent field (nSCF) theory as well as to osmotic, SFA, and AFM data. While the nSCF model correctly predicts the observed transition from a brush to a block profile, experimentally it occurs at a pressure 2 orders of magnitude lower than the simulations would suggest. The results acquired through simulation are consistent with available osmotic pressure data; however, SFA and AFM measurements are consistent with the neutron reflection experimental data presented here. This significant disagreement between the two data sets indicates that in a confined system the effective osmotic counter pressure to an applied mechanical pressure is much less than the osmotic pressure expected from the local polymer concentration.
    Macromolecules 04/2015; 48(7):2224-2234. DOI:10.1021/ma502246r · 5.80 Impact Factor
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    ABSTRACT: The interactions between the strong polyelectrolyte sodium poly(styrene sulfonate), NaPSS, and the neutral polymer poly(vinyl pyrrolidone), PVP, were investigated in bulk and at the silica/solution interface using a combination of diffusion NMR, SANS, solvent relaxation NMR and ellipsometry. We show for the first time that complex formation occurs between NaPSS and PVP in solution; the complexes formed were shown not to be influenced by pH variation, whereas increasing the ionic strength increases the complexation of NaPSS but does not influence the PVP directly. The complexes formed contained a large proportion of NaPSS. Study of these interactions at the silica interface demonstrated that complexes also form at the nanoparticle interface where PVP is added in the system prior to NaPSS. For a constant PVP concentration and varying NaPSS concentration, the system remains stable until NaPSS is added in excess, which leads to depletion flocculation. Surface complex formation using the layer-by-layer technique was also reported at a planar silica interface.
    Langmuir 03/2015; 31(14). DOI:10.1021/la503870b · 4.46 Impact Factor
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    ABSTRACT: The intestinal mucus gel layer represents a stumbling block for drug adsorption. This study is aimed to formulate a nanoparticulate system able to overcome this barrier by cleaving locally the glycoprotein substructures of the mucus. Mucolytic enzymes such as papain (PAP) and bromelain (BRO) were covalently conjugated to poly(acrylic acid) (PAA). Nanoparticles (NPs) were then formulated via ionic gelation method and characterized by particle size, zeta potential, enzyme content and enzymatic activity. The NPs permeation quantified by rotating tube studies was correlated with changes in the mucus gel layer structure determined by pulsed-gradient-spin-echo NMR (PGSE-NMR), small-angle neutron scattering (SANS) and spin-echo SANS (SESANS). PAP and BRO functionalized NPs had an average size in the range of 250 and 285 nm and a zeta potential that ranged between -6 and -5 mV. The enzyme content was 242 μg enzyme/mg for PAP modified NPs and 253 μg enzyme/mg for BRO modified NPs. The maintained enzymatic activity was 43% for PAP decorated NPs and 76% for BRO decorated NPs. The rotating tube technique revealed a better performance of BRO decorated NPs compared to PAA decorated NPs, with a 4.8 fold higher concentration of NPs in the inner slice of mucus. Addition of 0.5wt% of enzyme functionalized NPs to 5wt% intestinal mucin led to c.a. 2 fold increase in the mobility of the mucin as measured by PGSE-NMR indicative of a significant break-up of the structure of the mucin. SANS and SESANS measurements further revealed a change in structure of the intestinal mucus induced by the incorporation of the functionalized NPs mostly occurring at a lengthscale longer than 0.5 μm. Accordingly, BRO decorated NPs show higher potential then PAP functionalized NPs as mucus permeating drug delivery systems. Copyright © 2015. Published by Elsevier B.V.
    European Journal of Pharmaceutics and Biopharmaceutics 02/2015; DOI:10.1016/j.ejpb.2015.01.008 · 3.38 Impact Factor
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    ABSTRACT: Multiple particle tracking (MPT) methodology was used to dissect the impact of nanoparticle surface charge and size upon particle diffusion through freshly harvested porcine jejunum mucus. The mucus was characterised rheologically and by atomic force microscopy. To vary nanoparticle surface charge we used a series of self-assembly polyelectrolyte particles composed of varying ratios of the negatively charged polyacrylic acid polymer and the positively charged chitosan polymer. This series included a neutral or near-neutral particle to correspond to highly charged but near-neutral viral particles that appear to effectively permeate mucus. In order to negate the confounding issue of self-aggregation of such neutral synthetic particles a sonication step effectively reduced particle size (to less than 340nm) for a sufficient period to conduct the tracking experiments. Across the polyelectrolyte particles a broad and meaningful relationship was observed between particle diffusion in mucus (×1000 difference between slowest and fastest particle types), particle size (104-373nm) and particle surface charge (-29mV to +19.5mV), where the beneficial characteristic promoting diffusion was a neutral or near-neutral charge. The diffusion of the neutral polyelectrolyte particle (0.02887cmS(-1)×10(-9)) compared favourably with that of a highly diffusive PEGylated-PLGA particle (0.03182cm(2)S(-1)×10(-9)), despite the size of the latter (54nm diameter) accommodating a reduced steric hindrance with the mucin network. Heterogeneity of particle diffusion within a given particle type revealed the most diffusive 10% sub-population for the neutral polyelectrolyte formulation (5.809cm(2)S(-1)×10(-9)) be faster than that of the most diffusive 10% sub-populations obtained either for the PEGylated-PLGA particle (4.061cm(2)S(-1)×10(-9)) or for a capsid adenovirus particle (1.922cm(2)S(-1)×10(-9)). While this study has used a simple self-assembly polyelectrolyte system it has substantiated the pursuance of other polymer synthesis approaches (such as living free-radical polymerisation) to deliver stable, size-controlled nanoparticles possessing a uniform high density charge distribution yielding net neutral surface potential. Such particles that will provide an additional strategy to that of PEGylated systems where the interactions of mucosally delivered nanoparticles with the mucus barrier are to be minimised. Copyright © 2015. Published by Elsevier B.V.
    European Journal of Pharmaceutics and Biopharmaceutics 02/2015; DOI:10.1016/j.ejpb.2015.01.023 · 3.38 Impact Factor
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    ABSTRACT: The present review provides an overview of methods and techniques for studying interactions of micro- and nanoparticulate drug delivery system with mucus. Nanocarriers trapped by mucus are featuring a change in particle size and zeta potential that can be utilized to predict their mucus permeation behavior. Furthermore, interactions between nanoparticulate drug delivery systems and mucus layer modify the viscoelasticity of mucus which can be detected via rheological studies and quartz crystal microbalance with dissipation monitoring (QCM-D) analysis. To have a closer look at molecular interactions between drug carrier and mucus small-angle neutron scattering (SANS) is an appropriate analysis technique. Moreover, different methods to determine particle diffusion in mucus such as the newly established Transwell diffusion system, rotating silicone tube technique, multiple-particle tracking (MPT) and diffusion NMR are summarized within this review. The explanations and discussed pros and cons of collated methods and techniques should provide a good starting point for all those looking forward to move in this interesting field. Copyright © 2015. Published by Elsevier B.V.
    European Journal of Pharmaceutics and Biopharmaceutics 01/2015; DOI:10.1016/j.ejpb.2015.01.005 · 3.38 Impact Factor
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    ABSTRACT: Gels can be formed by dissolving Fmoc-diphenylalanine (Fmoc-PhePhe or FmocFF) in an organic solvent and adding water. We show here that the choice and amount of organic solvent allows the rheological properties of the gel to be tuned. The differences in properties arise from the microstructure of the fibre network formed. The organic solvent can then be removed post-gelation, without significant changes in the rheological properties. Gels formed using acetone are meta-stable and crystals of FmocFF suitable for X-ray diffraction can be collected from this gel.
    Soft Matter 12/2014; DOI:10.1039/C4SM02256D · 4.03 Impact Factor
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    ABSTRACT: The surface functionalization of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) with various proteolytic enzymes (i.e., trypsin, papain, bromelain) via a two-step carbodiimide coupling method is presented. Depending on the initial Enzyme:NPs ratio, enzyme loadings up to 4.0 wt.%, 4.4 wt.% and 5.34 wt.% were achieved for trypsin, papain and bromelain, respectively. All three conjugated enzymes partially maintained their enzymatic activity after their coupling reaction with the NPs. NPs functionalized with papain and bromelain exhibited a three-fold higher permeability in porcine intestinal mucus compared to nonfunctionalized NPs whereas those conjugated with trypsin showed an almost two-fold higher permeability value. Measurements of the diffusion rates of intestinal mucin, using a nuclear magnetic resonance (NMR) technique, further confirmed these observations, as the enzyme-functionalized NPs were proven to be capable of disrupting the mucin gel structure. According to the reported results, the coupling of proteolytic enzymes to the PLGA NPs' surface largely increases the NPs mucus permeability, thus making it a potentially important mucus permeation strategy.
    10/2014; 4(4):1441013. DOI:10.1142/S179398441441013X
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    ABSTRACT: Self-sorting in low molecular weight hydrogels can be achieved using a pH triggered approach. We show here that this method can be used to prepare gels with different types of mechanical properties. Cooperative, disruptive or orthogonal assembled systems can be produced. Gels with interesting behaviour can be also prepared, for example self-sorted gels where delayed switch-on of gelation occurs. By careful choice of gelator, co-assembled structures can also be generated, which leads to synergistic strengthening of the mechanical properties.
    Nanoscale 09/2014; 6(22). DOI:10.1039/C4NR04039B · 7.39 Impact Factor
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    ABSTRACT: Optical flow cell reflectometry was used to study the adsorption of poly(vinylpyrrolidone) (PVP) to a silica surface and the subsequent surfactant adsorption and polymer desorption upon exposure to the anionic surfactant sodium dodecyl sulfate (SDS). We have studied these effects as a function of pH and surfactant concentration, but also for two different methods of silica preparation, O2 plasma and piranha cleaning. As a function of pH, a plateau in the amount adsorbed of ∼0.6 mg/m(2) is observed below a critical pH, above which the adsorption decreases to zero within 2-3 pH units. An increase in pH leads to dissociation of surface OH groups and a decreased potential for hydrogen bonding between the polymer and surface. For the plasma- and piranha-cleaned silica, the critical pH differs by 1-2 pH units, a reflection of the much larger amount of surface OH groups on piranha-cleaned silica (for a given pH). Subsequent rinsing of the adsorbed layer of PVP with an SDS solution leads to total or partial desorption of the PVP layer. Any remaining adsorbed PVP then acts as an adsorption site for SDS. A large difference between plasma- and piranha-cleaned silica is observed, with the PVP layer adsorbed to plasma-cleaned silica being much more susceptible to desorption by SDS. For a plasma-cleaned surface at pH 5.5, only 30% of the originally adsorbed PVP is remaining, while for piranha-cleaned silica, the pH can be increased to 10 before a similar reduction in the amount of adsorbed PVP is seen. For a given pH, piranha-cleaned silica has a higher surface charge, leading to a smaller amount of adsorbed SDS per PVP chain on a piranha-cleaned surface compared to a plasma-cleaned surface under identical conditions. In that way, the high negative surface charge makes desorption by negatively charged SDS more difficult. The high surface charge thus protects the neutral polymer from surfactant-mediated desorption.
    Langmuir 07/2014; 30(28). DOI:10.1021/la501877v · 4.46 Impact Factor
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    ABSTRACT: The weak polyelectrolyte sodium polyacrylate, NaPA, and the neutral poly(vinyl pyrrolidone), PVP, were combined and the effects of complexation both in solution and at the nanoparticle interface were studied under basic pH conditions. Using a combination of SANS and PCS, we demonstrate that attractive interpolymer interactions occur between PVP and NaPA in solution (for polymers with molecular weights equal to 40 K and 60 K respectively); typically, no attractive interactions between PVP and NaPA are reported above a critical pH of 4-5. Polymer interactions in the bulk are observed between the larger molecular weight polymers studied. The mass ratios of polymer also affect the interactions in the bulk, indicating that polymer interactions are influenced by the charges present in the system. The addition of NaPA to a silica dispersion with PVP previously adsorbed to the particles is shown to led to polymer desorption and the destabilisation of the system leading to particle aggregation or even flocculation. SANS data show that the interparticle potential changes from being repulsive with bare silica or PVP-coated silica to attractive on addition of NaPA. The molecular weight of PVP is seen to affect the amount of polymer desorbed, whereas the molecular weight of NaPA had an effect on the aggregation of particles.
    Colloids and Surfaces A Physicochemical and Engineering Aspects 05/2014; 449(1):57–64. DOI:10.1016/j.colsurfa.2014.02.039 · 2.75 Impact Factor
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    ABSTRACT: An increasing human population requires a secure food supply and a cost effective, oral vaccine delivery system for livestock would help facilitate this end. Recombinant antigen adsorbed onto silica beads and coated with myristic acid, was released (∼15% (w/v)) over 24h at pH 8.8. At pH 2, the myristic acid acted as an enteric coating, protecting the antigen from a variety of proteases. The antigen adsorbed onto silica particles, coated in myristic acid had a conserved secondary structure (measured by circular dichroism (CD) spectroscopy) following its pH-triggered release. Small angle neutron scattering (SANS) was used to measure the thickness of the adsorbed antigen, finding that its adsorbed conformation was slightly greater than its solution radius of gyration, i.e. 120-160Å. The addition of myristic acid led to a further increase in particle size, with scattering data consistent with an acid thickness slightly greater than a monolayer of fully extended alkyl chains and a degree of hydration of around 50%. Whilst adsorbed onto the silica and coated in myristic acid, the protein was stable over 14 days at 42°C, indicating a reduced need for cold chain storage. These data indicate that further investigation is warranted into the development of this technology.
    International Journal of Pharmaceutics 03/2014; 468(1-2). DOI:10.1016/j.ijpharm.2014.03.046 · 3.65 Impact Factor
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    ABSTRACT: We discuss the effect of the kinetics of pH change on the mechanical properties of dipeptide hydrogels. Data from other peptide-based low molecular weight gelator (LMWG) systems suggest that the rheological properties are often highly dependent on the assembly rate. To examine kinetics here, we have used the hydrolysis of glucono-δ-lactone (GdL). The hydrolysis of GdL to gluconic acid results in a decrease in pH, the rate of which is temperature sensitive. Hence, we can adjust the rate of pH decrease, whilst achieving the same absolute final pH. Our data shows that at all temperatures the rheological profile is very similar, with an increase to a plateau, followed by a second increase in moduli, despite very different kinetics of assembly. Surprisingly, the final mechanical properties are very similar in all cases. We also show that the structures formed at the plateau can be accessed by adjusting the pH using CO2. By carefully balancing the pKa of the gelator with the pH achievable using CO2, flexible hydrogel membranes can be formed as opposed to a bulk gel. The rheological characteristics of the membranes are typical of a highly entangled polymer network. These membranes can be rigidified by post-addition of GdL to further lower the pH.
    Faraday Discussions 07/2013; DOI:10.1039/C3FD00104K · 4.61 Impact Factor
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    ABSTRACT: The effects of a nonionic alcohol ethoxylate surfactant, C(13)E(7), on the interactions between PVP and SDS both in the bulk and at the silica nanoparticle interface are studied by photon correlation spectroscopy, solvent relaxation NMR, SANS, and optical reflectometry. Our results confirmed that, in the absence of SDS, C(13)E(7) and PVP are noninteracting, while SDS interacts strongly both with PVP and C(13)E(7) . Studying interfacial interactions showed that the interfacial interactions of PVP with silica can be manipulated by varying the amounts of SDS and C(13)E(7) present. Upon SDS addition, the adsorbed layer thickness of PVP on silica increases due to Coulombic repulsion between micelles in the polymer layer. When C(13)E(7) is progressively added to the system, it forms mixed micelles with the complexed SDS, reducing the total charge per micelle and thus reducing the repulsion between micelle and the silica surface that would otherwise cause the PVP to desorb. This causes the amount of adsorbed polymer to increase with C(13)E(7) addition for the systems containing SDS, demonstrating that addition of C(13)E(7) hinders the SDS-mediated desorption of an adsorbed PVP layer.
    Langmuir 03/2012; 28(15):6282-90. DOI:10.1021/la300282m · 4.46 Impact Factor
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    ABSTRACT: The surfactant-mediated desorption of adsorbed poly(vinylpyrrolidone), PVP, from anionic silica surfaces by sodium dodecyl sulfate, SDS, was observed. While photon correlation spectroscopy shows that the size of the polymer-surfactant-particle ensemble grows with added SDS, a reduction in the near-surface polymer concentration is measured by solvent relaxation NMR. Volume fraction profiles of the polymer layer extracted from small-angle neutron scattering experiments illustrate that the adsorbed polymer layer has become more diffuse and the polymer chains more elongated as a result of the addition of SDS. The total adsorbed amount is shown to decrease due to Coulombic repulsion between the surfactant-polymer complexes and between the complexes and the anionic silica surface.
    Langmuir 12/2011; 28(5):2485-92. DOI:10.1021/la204512d · 4.46 Impact Factor

Publication Stats

36 Citations
62.96 Total Impact Points


  • 2013–2015
    • University of Greenwich
      • Department of Pharmaceutical, Chemical & Environmental Sciences
      Londinium, England, United Kingdom
  • 2014
    • University of Sussex
      • School of Life Sciences
      Brighton, England, United Kingdom
  • 2011–2014
    • University of Bristol
      • School of Chemistry
      Bristol, England, United Kingdom