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Encapsulation of active compounds such as nutraceuticals or preservatives increases their concentration, bioavailability and stability in food products. Nanoparticle carriers are an effective encapsulation method that provides protection from environmental degradation agents and control over the rate of compound release. This review focuses on the parameters affecting transport in a number of nanoparticle types used in (or with the potential for) food and beverage applications: Emulsions and Pickering emulsions, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), liposomes, and colloidosomes. Emphasis is placed on the effect of medium conditions, nanoparticle structure and size, and the role of the shell.

Active compounds such as flavors, scents, vitamins or nutraceuticals enhance the quality and nutritional value of foods. Their encapsulation in nanoparticles preserves properties such as appearance, while increasing solubility and bioavailability. Nanostructured lipid carriers (NLC) composed of liquid and solid lipid domains are biocompatible and combine high encapsulation rates with mechanical stability. In this paper we use Monte Carlo simulations to investigate the effects of the solid domain properties on the rate of compound release from NLC. Quite surprisingly, solid impenetrable domains at the particle/solution interface hinder release only when the domain size is much smaller than the nanoparticle size, even if they cover a significant fraction of the interface. The geometry of the solid domains also affects the rate of release, and how the rate dependence on domain size and fraction.

Kappa-casein (κCN) and beta-casein (βCN) are disordered proteins present in mammalian milk. In vitro, βCN self-assembles into core-shell micelles. κCN self assembles into similar micelles, as well as into amyloid-like fibrils. Recent studies indicate that fibrillization can be suppressed by mixing βCN and κCN, but the mechanism of fibril inhibition has not been identified. Examining the interactions of native and reduced kappa-caseins (N-κCN and R-κCN) with βCN, we expose a competition between two different self-assembly processes: micellization and fibrillization. Quite surprisingly, however, we find significant qualitative and quantitative differences in the self-assembly between the native and reduced κCN forms. Specifically, thermodynamic analysis reveals exothermic demicellization for βCN and its mixtures with R-κCN, as opposed to endothermic demicellization of N-κCN and its mixtures with βCN at the same temperature. Furthermore, with time, R-κCN/βCN mixtures undergo phase separation into pure βCN micelles and R-κCN fibrils, while in the N-κCN/βCN mixtures fibril formation is considerably delayed and mixed micelles persist for longer periods of time. Fibrils formed in N-κCN/βCN mixtures are shorter and more flexible than those formed in R-κCN/βCN systems. Interestingly, in the N-κCN/βCN mixtures, the sugar moieties of N-κCN oligomers seem to organize on the mixed micelles surface in a manner similar to the organization of κCN in milk casein micelles.

Peroxyl radical sensitive fluorescent dye (BODIPY 665/676) encapsulated nanostructured lipid carriers (NLCs) were prepared by blending solid (eicosane) and liquid (glyceryl trioctanoate) lipid in various proportions (10:90, 30:70, 50:50, 100:0 liquid: solid). Peroxyl radical transport rate was measured by adding 20 mmol/l 2,2′-azobis-2-methyl-propanimidamide, dihydrochloride in the aqueous phase. Fluorescence imaging of NLCs revealed that fluorescent dye was distributed in the liquid lipid regions of 10 and 30% NLCs. However, 50% NLC resembled NLCs with 100% liquid lipid in that, little or no solid domains were observed and the dye was more or less uniformly distributed. Peroxyl radical transport was in the order, 100%

Oscillating fields such as electrostatic or ultrasound are frequently used to induce release from nano and microcapsule carriers, but the effect of the field frequency has not been examined to date. This paper presents the results of Monte Carlo simulations for the release rate of encapsulated compounds from core–shell microcapsules subjected to an oscillating field. We find that the release rate approaches that of the permanently permeable case when the oscillation frequency is relatively high, even if the fraction of time the shell is permeable is 50% or less. Examination of the distribution of encapsulated molecules in the core shows that they rearrange during the impermeable part of the cycle, thereby enriching the shell/solution boundary and increasing the driving force for release in the next permeable part of the cycle.

Phospholipids, block copolymers and surfactants are surface-active molecules that assemble into bilayer structures in aqueous solutions, forming nanoscale vesicles: phospholipid-based liposomes, polymer-based polymersomes, or surfactant-based niosomes. These vesicles are highly versatile and can be used for the delivery of pharmaceutical agents—enabling targeted and controlled release while shielding the encapsulated drugs from environmental degradation agents and the immune system. The performance of vesicle-based drug carriers has been shown to depend on both their constituent chemistry (e.g., surface moieties) and their physical properties (size, shape). This review examines the characteristics of vesicle-based formulations and their application to biomedical applications ranging from cancer therapies to delivery across the blood–brain barrier (BBB).

Nucleic acid–based therapies use DNA or siRNA to treat genetic disorders caused by gene abnormality, such as hemoglobinopathies (sickle cell disease, beta-thalassemia), cystic fibrosis, or some types of cancer. Complexes between nucleic acids and cationic phospholipids, lipoplexes, are a promising, synthetic gene carrier for both in vitro and in vivo applications. However, optimization of the complex performance requires better understanding and control of lipoplex properties. Lipoplex structure is characterized on two lengths. On the local scale, namely, 10–50 nm, the lipid and nucleic acid arrangement is set by thermodynamic equilibrium and is directly linked to the molecular properties of the lipids and concentration of nucleic acid. On larger scales, in the order 100 nm–1 μm, lipoplex characteristics are set by the kinetics of the synthesis process, following a three-step process: (1) an initial stage (on timescales of less than 1 min) where the nucleic acid adsorbs onto the lipid assembly; (2) a growth stage, where complexes flocculate, characterized by a broad range of timescales from minutes to hours, depending on system parameters; and (3) internal equilibration stage where the outer lipoplex structure remains constant, which may take hours or more.

The stability of active compounds encapsulated in nanoparticles depends on the resistance of the particles to diffusion of environmental degradation agents. In this paper, off-lattice Monte Carlo simulations are used to investigate a suspension of nanostructured lipid carriers (NLC) composed of interspaced liquid and solid lipid domains, immersed in a solution containing molecules representing oxidative or other degradation agents. The simulations examine the diffusion of the degradation agents into the nanoparticles as a function of nanoparticle size, solid domain fraction, and domain size. Two types of suspensions are studied: one (representing an infinitely dilute nanoparticle suspension) where the concentration of oxidative agents is constant in the solution around the particle and the other, finite system where diffusion into the nanoparticle causes depletion in the concentration of degradation agents in the surrounding solution. The total number of degradation agent molecules in the NLCs is found to decrease with the solid domain fraction, as may be expected. However, their concentration in the liquid domains is found to increase with the solid domain fraction. Since the degradation reaction depends on the concentration of the degradation agents, this suggests that compounds encapsulated in nanoparticles with high liquid content (such as emulsions) will degrade less and be more stable than those encapsulated in NLCs with high solid domain fraction, in agreement with previous experimental results.

Emulsions, solid lipid nanoparticles (SLN), and nanostructured lipid carriers (NLC) containing a mix of liquid and solid domains are of interest as encapsulation vehicles for hydrophobic compounds. Studies of the release rate from these particles yield contradictory results: Some find that increasing the fraction of solid phase increases the rate of release and others the opposite. In this paper we study the release of encapsulated materials from lipid-based nanoparticles using Monte Carlo simulations. We find that, quite surprisingly, the release rate is largely insensitive to the size of solid domains or the fraction of solid phase. However, the distribution of the domains significantly affects the rate of release: Solid domains located at the interface with the surrounding solution inhibit transport, while nanoparticles where the solid domains are concentrated in the center enhance it. The latter can lead to release rates in NLCs that are faster than in the equivalent emulsions. We conclude that controlling the release rate from NLCs requires the ability to determine the location and distribution of the solid phase, which may be achieved through choice of the surfactants stabilizing the particles, incorporation of nucleation sites, and/or the cooling rates and temperatures.

Recent interest is focused on microcapsules stabilized using colloidal nanoparticles – termed ‘colloidosomes – for encapsulation applications in food, drug and cosmetic industries. However, due to electrostatic repulsion between similarly charged particles, shells composed of single-type nanoparticles tend to be monolayer-thick and relatively permeable. We investigated a self-assembly method for controlling the permeability of colloidal shells using aggregates composed of oppositely charged silica nanoparticles. Using a combination of rapid fluorescence based method and theoretical diffusion models, we found that colloidosomes whose shells contained colloidal silica aggregates displayed lower permeability to peroxyl radicals than ones stabilized by single type of silica nanoparticles. Furthermore, the permeability varied as a function of the ratio of oppositely charged silica nanoparticles in the shell. The ability to control the permeability of colloidosomes, while using a simple self-assembly synthesis method, will enable enhanced control over release kinetics and oxidative stability of encapsulants.

We present a theoretical model that relates transport through a colloidal shell to the shell thickness, packing density, the colloidal particle size, and polydispersity. The model addresses two cases: Self-assembled monolayer shells and fused shells. In the former case, the shell thickness is equal to the colloidal particle diameter, and the packing density is determined by adsorption thermodynamics. In the latter case, the shell thickness may be several times that of the particle dimensions, and the packing density is set by the fusion process. We find that the pores formed by close-packing of the particles in the shell enable size exclusion, namely, prohibit transport of diffusants larger than a critical size. As may be expected, the critical dimension for size selectivity is proportional to the colloidal particle radius, and decreases with packing density. For diffusants smaller than the size-exclusion limit, we find that the rate of transport decreases with increasing packing density of particles in t...

The encapsulation of active compounds such as nutraceuticals, flavors, or antimicrobial agents in nanoparticle carriers addresses multiple issues in food and beverage applications. It can increase the effective concentration of compounds with limited solubility, and protect them from environmental degradation agents such as pH, enzymes, or free radicals. Nanocarriers can increase the bioavailability of nutrients, and be engineered to release their cargo in a manner that suits specific applications. This review examines the structure and properties of different nanoparticles appropriate for foods, including emulsions, Pickering emulsions, and microemulsions, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), liposomes, polymersomes, colloidosomes, and nanogels.

Effective therapies require an efficient method for drug delivery. The main goals of drug delivery systems, or carriers, is to enhance therapeutic efficiency by targeting specific tissue, and to provide control over the rate of drug release. Core–shell vesicle drug carriers are based on bilayer-forming amphiphiles: liposomes composed of phospholipid bilayers, polymersomes composed of copolymers, and niosomes from nonionic surfactants. Designed to carry hydrophilic drugs, they offer, in addition to targeting and controlled release, protection of drugs from degradation, prolonged circulation time in vivo, and administration routes that are incompatible with the unmodified drugs. Extensive studies link delivery efficiency to the carrier size, shape, and surface chemistry and charge, as well as environmental conditions (temperature, pH) and cell type. This review discusses the three types of formulations and summarizes studies of their performance in biomedical applications such as cancer therapy (tumor targeting) or transport through the blood–brain barrier (BBB).

Gene therapy and gene silencing techniques are based on the insertion of nucleic acids (DNA or siRNA) into cells, with the goal of inducing therapeutic changes in cell functions. The need for carriers to facilitate this transfection process led to the study of lipid-nucleic acid assemblies, such as lipoplexes. The efficacy of lipoplexes is linked to their structure: the local, nanoscale structure of lipoplexes is an equilibrium feature, determined by lipid properties and complex composition. Larger-scale characteristics are, however, controlled by the assembly route and kinetics. This chapter reviews the equilibrium properties of lipoplexes and the kinetics pathways for their formation. Better understanding of lipoplex formation can not only lead to the design of effective nucleic acid lipoplex-based gene delivery or silencing agents, but is also of interest as a fundamental multicomponent, multilength-scale and multitime scale process.

At the critical micelle concentration (CMC), amphiphiles self-assemble into spherical micelles, typically followed by a transition at the second CMC to cylindrical micelles that are uniform in width but are polydispersed in length and have swollen ends. In this Letter, we report on a new structural path of self-assembly that is based on discoidal (coin-like), rather than spherical, geometry; the nonionic sterol ChEO10 is shown to form monodisperse equilibrium disc assemblies at the first CMC, transitioning at the second CMC into flat ribbons that (like the cylindrical micelles) have uniform width, polydispersed length, and swollen ends. Increase in ChEO10 concentration or the temperature leads to ribbon elongation, branching, and network formation. This self-assembly path reveals that (1) surfactants can form equilibrium nonspherical assemblies at the CMC and (2) aggregate progression around the second CMC is similar for the disc and sphere geometries.

This paper discusses various interactions between ultrasound, phospholipid monolayer-coated gas bubbles, phospholipid bilayer vesicles, and cells. The paper begins with a review of microbubble physics models, developed to describe microbubble dynamic behavior in the presence of ultrasound, and follows this with a discussion of how such models can be used to predict inertial cavitation profiles. Predicted sensitivities of inertial cavitation to changes in the values of membrane properties, including surface tension, surface dilatational viscosity, and area expansion modulus, indicate that area expansion modulus exerts the greatest relative influence on inertial cavitation. Accordingly, the theoretical dependence of area expansion modulus on chemical composition - in particular, poly (ethylene glyclol) (PEG) - is reviewed, and predictions of inertial cavitation for different PEG molecular weights and compositions are compared with experiment. Noteworthy is the predicted dependence, or lack thereof, of inertial cavitation on PEG molecular weight and mole fraction. Specifically, inertial cavitation is predicted to be independent of PEG molecular weight and mole fraction in the so-called mushroom regime. In the “brush” regime, however, inertial cavitation is predicted to increase with PEG mole fraction but to decrease (to the inverse 3/5 power) with PEG molecular weight. While excellent agreement between experiment and theory can be achieved, it is shown that the calculated inertial cavitation profiles depend strongly on the criterion used to predict inertial cavitation. This is followed by a discussion of nesting microbubbles inside the aqueous core of microcapsules and how this significantly increases the inertial cavitation threshold. Nesting thus offers a means for avoiding unwanted inertial cavitation and cell death during imaging and other applications such as sonoporation. A review of putative sonoporation mechanisms is then presented, including those involving microbubbles to deliver cargo into a cell, and those - not necessarily involving microubbles - to release cargo from a phospholipid vesicle (or reverse sonoporation). It is shown that the rate of (reverse) sonoporation from liposomes correlates with phospholipid bilayer phase behavior, liquid-disordered phases giving appreciably faster release than liquid-ordered phases. Moreover, liquid-disordered phases exhibit evidence of two release mechanisms, which are described well mathematically by enhanced diffusion (possibly via dilation of membrane phospholipids) and irreversible membrane disruption, whereas liquid-ordered phases are described by a single mechanism, which has yet to be positively identified. The ability to tune release kinetics with bilayer composition makes reverse sonoporation of phospholipid vesicles a promising methodology for controlled drug delivery. Moreover, nesting of microbubbles inside vesicles constitutes a truly “theranostic” vehicle, one that can be used for both long-lasting, safe imaging and for controlled drug delivery.

We examined the effect of bilayer composition on membrane sensitivity to low-frequency ultrasound (LFUS) in bilayers composed of ternary mixtures of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), dipalmitoyl-phosphocholine (DPPC), and cholesterol. The phase diagram of this system does not display macroscopic phase coexistence between liquid phases (although there are suggestions that there is coexistence between a liquid and a solid phase). Samples from across the composition space were exposed to 20 kHz, continuous wave ultrasound, and the response of the bilayer was quantified using steady-state fluorescence spectroscopy to measure the release of a self-quenching dye, calcein, from large unilamellar vesicles. Dynamic light scattering measurements indicate that, in this system, release proceeds primarily by transport through the vesicle bilayer. While vesicle destruction might account, at least in part, for the light scattering trends observed, evidence of destruction was not as obvious as in other lipid systems. Values for bilayer permeability are obtained by fitting release kinetics to a two-film theory mathematical model. The permeability due to LFUS is found to increase with increasing DPPC content, as the bilayer tends toward the solid-ordered phase. Permeability, and thus sensitivity to LFUS, decreases with either POPC or cholesterol mole fractions. In the liquid regime of this system, there is no recorded phase transition; thus cholesterol is the determining factor in release rates. However, the presence of domain boundaries between distinctly differing phases of liquid and solid is found to cause release rates to more than double. The correlation of permeability with phase behavior might prove useful in designing and developing therapies based on ultrasound and membrane interactions.

Colloidosomes, namely, microcapsules coated by a colloidal shell, have been widely studied as potential carriers of active compounds for various applications. The colloidal shell differs from the shells of other ‘somes’ (liposomes, polymersomes) since it is a composite material with an impenetrable phase—the particles, and a penetrable one—the voids or pores between them. Recent analysis shows that in the shells composed of monodisperse and charged particles, the maximal volume fraction of colloids in the self-assembled layer depends on the size ratio between the particle's hard-sphere radius and the effective radius, which includes the range of repulsive electrostatic interactions. Thus, somewhat counter-intuitively, the density of particles in the shell increases with increasing particle radius. However, mixing particle sizes can lead to highly packed shells where the impenetrable phase volume fraction approaches 100%. The diffusional flux through the colloidal shell is highly sensitive to the packing density (or particle volume fraction); this parameter sets the average size of the pores, their distribution through the shell, and their tortuosity. However, while in thick multi-layer shells the flux increases with increasing particle size, in the case of monolayer-thick shells there is no apparent dependence of the flux on the colloid dimensions.

Coating hydrogel films or microspheres by an adsorbed colloidal shell is one synthesis method for forming colloidosomes. The colloidal shell allows control of the release rate of encapsulated materials, as well as selective transport. Previous studies found that the packing density of self-assembled, adsorbed colloidal monolayers is independent of the colloidal particle size. In this paper we develop an equilibrium model that correlates the packing density of charged colloidal particles in an adsorbed shell to the particle dimensions in monodisperse and bidisperse systems. In systems where the molar concentration in solution is fixed, the increase in adsorption energy with increasing particle size leads to a monotonic increase in the monolayer packing density with particle radius. However, in systems where the mass fraction of the particles in the adsorbing solutions is fixed, increasing particle size also reduces the molar concentration of particles in solution, thereby reducing the probability of adsorption. The result is a nonmonotonic dependence of the packing density in the adsorbed layer on the particle radius. In bidisperse monolayers composed of two particle sizes, the packing density in the layer increases significantly with size asymmetry. These results may be utilized to design the properties of colloidal shells and coatings to achieve specific properties such as transport rate and selectivity.

Colloidosomes are aqueous cores surrounded by a shell composed of packed colloidal particles. Recent studies suggest that these colloidal shells reduce, or even inhibit, the transport of molecular species (diffusants). However, the effect of the colloidal shell on transport is unclear: In some cases, the reduction in transport of diffusants through the shell was found to be independent of the size of the colloidal particles composing the shell. Other studies find, however, that shells composed of small colloidal particles of order 100 nm or less hindered transport of diffusants more than those composed of micro-scale colloidal particles. In this paper we present a simple diffusion model that accounts for three processes that reduce diffusant transport through the shell: (i) a reduction in the penetrable volume available for transport, which also increases the tortuousity of the diffusional path, (ii) narrow pore size which may hinder transport for larger diffusants through size exclusion, and (iii) a reduction in interfacial area due to ‘blocking’ of the surface by the adsorbed particles. We find that the colloidal particle size does not affect the reduction in transport through the colloidal shell when the shell is a monolayer. However, in closely packed, thick layers where the thickness of the multi-layer shell is fixed, the rate of transport decreases significantly with colloidal particle dimensions. These results are in excellent agreement with previously published experimental results.

Colloidosomes are composed of an aqueous or hydrogel corethat is coated by a semi-permeable colloidal shell. The properties of the shell can be varied to control the rate of release of encapsulated components such as drugs. Specifi-cally, the pores formed between the colloidal particles suppress transport of large components, while allowing diffusion of smaller ones. Self-assembly of colloidal particles on hydrogel films is a convenient method forcolloidosome synthesis, but to date little is known regarding the effect (if any) of the encapsulated drug on the shell packing density. In this paper we examined self-assembly of colloidal shells on alginate films containing four model drugs: aspirin, caffeine, theophylline and theobromine. We find that the packing density in the colloidal shells is low for all drugs, and ranges between 0.16 and 0.3. There is no clear correlation between drug properties (in particular, water solubility) and the packing density of the self-assembled colloidal shell.

The compositional differences between domains in phase-separated membranes are associated with differences in bilayer thickness and moduli. The resulting packing deformation at the phase boundary gives rise to a line tension, the one dimensional equivalent of surface tension. In this paper we calculate the line tension between a large membrane domain and a continuous phase as a function of the thickness mismatch and the contact angle between the phases. We find that the packing-induced line tension is sensitive to the contact angle, reaching a minimum at a specific value. The difference in the line tension between a flat domain (that is within the plane of the continuous phase) and a domain at the optimal contact angle may be of order 40%. This could explain why previous calculations of the thickness mismatch based line tension tend to yield values that are higher than those measured experimentally.

The synthesis of metal nanoclusters in a polymeric environment has been shown to yield nearly monodisperse particles, whose size is controlled by the strength of the polymer/metal interactions. Although the phenomenon is quite general, little is known regarding the mechanism by which the polymer controls nanocluster size. Previous studies of the kinetics of nanocluster growth in polymeric melts above the glass transition temperature (Tg) suggest that the nanoparticle size is set by the critical cluster size (nucleation stage) rather than the rate of metal precursor transport, namely, growth. In this paper, we examine the kinetics of iron oxide (Fe2O3) nanocluster formation below the glass temperature (Tg) in two polymer melts: polystyrene (PS) and poly(methyl methacrylate) (PMMA). We find that the morphology of the nanoclusters formed below Tg is highly sensitive to the system temperature and differs significantly from the morphology above Tg. However, the kinetics of cluster formation is exponential wit...

Membrane inhomogeneity gives rise to a perturbation energy that may be manifested as line tension between regions of different compositions. Here we calculate the perturbation energy of a phase-separated fluid membrane composed of domains embedded in a continuous phase and relate it to the line tension in the system. We find that the effective line tension due to the thickness mismatch between the phases varies nonmonotonically as a function of the domain size and spacing when those decrease below about 20 nm. Although we find that the characteristic time scale for domain coalescence increases with domain size, the coalescence time for domains on the order of 25 to 50 nm may be as long as several days. The time scale for domain coalescence is found, quite surprisingly, to be maximal when the bending and area moduli of the domain and continuous phase are similar and to decrease when one phase is stiffer than the other. Domain stability is also found to vary as a function of spacing; as a result, small domains on the order of 5 nm become unstable and tend to coalesce when the domain-phase area fraction increases above 0.5, whereas larger domains on the order of 50 nm become unstable only when the area fraction increases above 0.8.

We investigate the effect of system properties and adsorption sequence on competitive adsorption of poly(methyl methacrylate) (PMMA) and polystyrene (PS) on narrowly polydispersed cobalt (Co) nanoparticles (D ∼ 27 nm). The adsorbed layer composition is studied using thermo-gravimetric analysis (TGA). We find that adsorbed layers of PS are completely displaced by PMMA when the solvent is a common good solvent. An adsorbed layer of only PMMA is also obtained through competitive adsorption from a common good solvent. However, in a selective solvent that is poor for PS, sequential adsorption leads to the formation of mixed layers.

We examine the release of two highly hydrophilic drugs, nicotine and caffeine, from poly(e-caprolactone) (PCL) matrices. We find that the dominant mechanism for drug release is drug diffusion through the PCL matrices. As a result, the rate of drug release (defined by the amount of drug released per unit time) decreases exponentially with time. Coating the drug-carrying particles with a drug-free PCL layer significantly changes the release profile: instead of exponential decay, the release rate exhibits a peak whose location (time) and magnitude vary with the diffusion coefficient of the drug in the polymer and the thickness of the coating. As a result, coating may be used to control the release rate andobtain a relatively constant rate over a period of time. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

Non-adherence with medication remains the major correctable cause of poor outcome in schizophrenia. However, few treatments have addressed this major determinant of outcome with novel long-term delivery systems.The aim of this study was to provide biological proof of concept for a long-term implantable antipsychotic delivery system in rodents and rabbits.Implantable formulations of haloperidol were created using biodegradable polymers. Implants were characterized for in vitro release and in vivo behavior using prepulse inhibition of startle in rats and mice, as well as pharmacokinetics in rabbits.Behavioral measures demonstrate the effectiveness of haloperidol implants delivering 1 mg/kg in mice and 0.6 mg/kg in rats to block amphetamine (10 mg/kg) in mice or apomorphine (0.5 mg/kg) in rats. Additionally, we demonstrate the pattern of release from single polymer implants for 1 year in rabbits.The current study suggests that implantable formulations are a viable approach to providing long-term delivery of antipsychotic medications in vivo using animal models of behavior and pharmacokinetics. In contrast to depot formulations, implantable formulations could last 6 months or longer. Additionally, implants can be removed throughout the delivery interval, offering a degree of reversibility not available with depot formulations.

Synthesis of metal nanoclusters in polymeric media has been shown to yield small clusters with a narrow size distribution. Embedding such clusters in the three-dimensional structures formed by diblock copolymers will allow the development of ordered structures with high optical and magnetic contrast between the different regions. In this paper we investigate the effect of homopolymer and diblock copolymer properties on the cluster size. We find that in homopolymer solutions, the cluster size reaches a minimum at a specific chain molecular weight (MW). In the case of diblock copolymers, the cluster size is set by the MW of the block with the stronger affinity to the metal surface.

Cylindrical micelles are known to exhibit two types of morphologies: branched networks and linear, worm-like (or thread-like) micelles. These structures correspond to two types of topological defects: end-caps and junction points. Although either type of defect increases the micelle energy (when compared to the cylindrical sections), they are stabilized by an increase in the translational (end-caps) or configurational (junctions) entropy. End-caps reduce the length of the cylindrical micelles, resulting in a suspension of linear, worm-like micelles. Y-junction branch points cause the formation of a network structure that may percolate and coexist thermodynamically with a "sol" of finite cylinders with end-caps. In this paper, we review current experimental and theoretical studies of non-ionic cylindrical micelles in aqueous solutions. We focus on single and multicomponent amphiphiles, and consider both small molecules and macromolecules (polymers), in order to identify the driving forces that determine the type of topological 'defect' and the resulting system morphology.

We investigate the formation of polymer vesicles, or polymersomes, of polystyrene-block-poly(ethylene oxide) diblock copolymers using double emulsion droplets of controlled architecture as templates. To engineer the structure of the polymersomes, it is important to consider the concentration of diblock copolymer in the middle phase of the double emulsion. We describe how the presence of excess polymer can induce a transition from complete wetting to partial wetting of the middle phase, resulting in polymer shells with inhomogeneous thicknesses.

The effect of a polymeric medium on the nucleation and growth kinetics of iron oxide (γ-Fe2O3) clusters is studied. We show that the kinetics in both poly(methyl methacrylate) and polystyrene are d...

The ability to design nanomaterial characteristics requires exact control of particle structure due to the sensitive relationship between the material properties and the particle size and morphology. Borrowing nature's approach where biomineralization is controlled by macromolecules, synthetic polymeric matrices are used to guide the formation of stable, monodisperse iron oxide nanoparticles uniformly distributed in the polymeric matrix. Particle size, size distribution, and morphology are determined by the polymer−particle interactions and are independent of the chain molecular weight: γ-Fe2O3 particles formed in strongly interacting polymeric media are small (∼10−20 nm) and pyramidal in shape, while those formed in weakly interacting media are larger (∼40−60 nm) and spherical. This synthesis method can be easily extended to a variety of inorganic nanoparticle chemistries, thereby enabling exact control over material properties.

We examine, using an analytical mean-field model, the distribution of cholesterol in a lipid bilayer. The model accounts for the perturbation of lipid packing induced by the embedded cholesterol, in a manner similar to that of transmembrane proteins. We find that the membrane-induced interactions between embedded cholesterol molecules vary as a function of the cholesterol content. Thus, the effective lipid-cholesterol interaction is concentration-dependent. Moreover, it transitions from repulsive to attractive to repulsive as the cholesterol content increases. As the concentration of cholesterol in the bilayer exceeds a critical value, phase separation occurs. The coexistence between cholesterol-rich and cholesterol-poor domains is universal for any bilayer parameters, although the composition of the cholesterol-rich phase varies as a function of the lipid properties. Although we do not assume specific cholesterol-lipid interactions or the formation of a lipid-cholesterol cluster, we find that the composition of the cholesterol-rich domains is constant, independent of the cholesterol content in the bilayer.

We examine here the adsorption of weak, acidic, rigid macro-ions onto oppositely charged surfaces using a mean field model. The analysis takes into account the effect of the nominal suspension pH on the charge distribution inside the macro-ion layer, as well as the counter-ion distribution in the adsorbed layer and in the solution surrounding the substrate. We find that, as expected, the adsorbed layer thickness decreases with the pH (namely, with the degree of charge dissociation) and with the solution ionic strength. The macro-ion adsorption can, in some cases, overcompensate for the substrate charge, thereby allowing layer-by-layer deposition. We find that charge inversion is obtained, for a given substrate, if the macro-ion pK is lower than a critical value. For a given macro-ion, charge inversion takes place if the substrate charge density exceeds a critical value that scales as the square root of the macro-ion charge density. In both cases charge inversion is obtained only in the regime where the suspension pH is comparable to the pK.

Although studies of charged hydrogel swelling focus on the swelling transition, hydrogels display pre‐transition swelling which may affect their performance in applications such as sensors. In this paper we investigate the effect of system parameters on the pre‐transition swelling of charged poly methacrylic acid (PMAA) hydrogels. We find that the pre‐transition swelling can be quite significant in magnitude (in our case ∼40% of the maximal swelling). Increasing the sub‐chain molecular weight increases swelling in the pre‐transition region only in the case where no salt is added; Contrary to expectation, in moderate ionic strength solutions the degree of swelling of longer chains is lower than that of shorter sub‐chains. Also contrary to expectation, in the case of longer sub‐chains the addition of salt decreases the gel volume in the pre‐transition region, thereby indicating that in this system a significant number of charges are dissociated. These trends can be understood by accounting for the ...

The commonly held model for membrane dissolution by detergents/surfactants requires lipid transport from the inner to the outer bilayer leaflet ('flip-flop'). Although applicable to many systems, it fails in cases where cross-bilayer transport of membrane components is suppressed. In this paper we investigate the mechanism for surfactant-induced solubilization of polymeric bilayers. To that end, we examine the dissolution of a series of increasingly thick, polymer-based vesicles (polymersomes) by a nonionic surfactant, Triton X-100, using dynamic light scattering. We find that increasing the bilayer thickness imparts better resistance to dissolution, so that the concentration required for solubilization, after a fixed amount of time, increases nearly linearly with membrane thickness. Combining our experimental data with a theoretical model, we show that the dominant mechanism for the surfactant-induced dissolution of polymeric vesicles, where polymer flip-flop across the membrane is suppressed, is the surfactant transport through the bilayer. This mechanism is different both qualitatively and quantitatively from the mechanisms by which surfactants dissolve pure lipid vesicles.

We examine experimentally and theoretically the effect of polymer adsorption layers on the stability of metal nanoclusters. We find that, somewhat contrary to expectation in this low volume fractio...

We present a model for the adsorption of charged rigid macroions such as dendrimers on oppositely charged substrates, accounting for small ion penetration into the adsorbed layers. We find that the first layer thickness and adsorbed amount decrease with salinity, but the degree of overcharging is maximized at a finite salt concentration. The thickness of subsequent layers is independent of the number of layers, nearly independent of the substrate charge, and decreases mildly with salinity.

We present a simple model for the solublization of hydrophobic colloidal particles, such as lipophilic drugs, in aqueous solutions through the use of bilayer-forming amphiphiles (surfactants or lipids). We predict that when the amphiphiles are in excess, there is a sharp transition from flocculated particles to dispersed ones. The system state (flocculated or dispersed particles) depends on the compressibility of the amphihphiles and their interaction energy with the particles. When the amphiphiles are not in excess, the volume fraction of solubilized particles is predicted to increase linearly with amphiphile concentration, with a slope that depends on amphiphile characteristics. These predictions are found to be in agreement with experimental observations.

The long-range forces controlling cell or bacteria adsorption onto substrates are governed by electrostatic interactions. In this paper we use a simple mean field model (Debye–Huckel) to examine the interactions between cells and surfaces. We model the cell interface as an ion-penetrable, charge-regulating layer, thereby accounting for the finite thickness of the cell's extra-cellular (glycocalyx) layer. We find that charge regulation leads to several non-intuitive trends regarding the repulsion between a cell and similarly charged substrates: (I) instead of increasing monotonically with decreasing cell–substrate separation, the pressure varies non-monotonically, and (II) instead of monotonically decreasing the repulsion (at contact) between the cell and the substrate, there is a regime where adding salt leads to an increase in the repulsion.

Targeted drug delivery requires binding to (and subsequent uptake by) the carrier and target cell. In this paper, we calculate the work required to bring into contact liposomal carriers and cells as a function of the liposome and cell electrostatic characteristics. We find that cell–liposome adhesion is sensitive to the cell type and optimized at a cell to liposome charge ratio which depends on the degree of cell charge regulation. As a result, uptake (which is dependent on the occurrence of binding) is also optimized. Incorporation of a (poly)ethylene glycol (PEG) layer enhances liposome adhesion in cases where the cell–liposome interactions are repulsive, and suppresses adhesion in systems where the interactions are attractive. Our results, which are in agreement with experimental observations, show that electrostatic interactions may be designed to enable targeted drug delivery by liposomes to a specific cell population.

In this study we use the Poisson−Boltzmann analysis in the Debye−Huckel limit to examine the effect of charge regulation on the interactions between similarly charged ion-penetrable adsorbed layers. We find that the magnitude of the interactions decays rapidly with the degree of charge regulation, although the decay length remains the Debye screening length. As a result, the interactions between charge-regulating layers are much weaker than those between strongly dissociated ones.