Compound Stability in Nanoparticles: The Effect of Solid Phase Fraction on Diffusion of Degradation Agents into Nanostructured Lipid Carriers.

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.

Competing processes of micellization and fibrillization in native and reduced casein proteins.

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.

From Discs to Ribbons Networks: The Second Critical Micelle Concentration in Nonionic Sterol Solutions.

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.

Effect of temperature and loading on the structure of β-casein/ibuprofen assemblies.

β-Casein is a 24 kDa amphiphilic and unstructured protein that self-assembles into small core-shell micelles at a wide range of concentrations, pH values and temperatures. We recently developed the micelles as nanocarriers for oral delivery of hydrophobic drugs. In this paper we examined the effect of the hydrophobic non-steroidal anti-inflammatory drug (NSAID) ibuprofen on the micellar structure, as a function of temperature and loading.

Drug release through liposome pores.

Electrical, ultrasound and other types of external fields are known to induce the formation of pores in cellular and model membranes. This paper examines drug release through field induced liposome pores using Monte Carlo simulations. We find that drug release rates vary as a function of pore size and spacing, as well as the overall fraction of surface area covered by pores: The rate of release from liposomes is found to increase rapidly with pore surface coverage, approaching that of the fully ruptured liposome at fractional pore areas.

Nanostructured lipid carriers: effect of solid phase fraction and distribution on the release of encapsulated materials.

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.

Structure and kinetics of lipid-nucleic acid complexes.

The structure and function of lipid-based complexes (lipoplexes) have been widely investigated as cellular delivery vehicles for nucleic acids-DNA and siRNA. Transfection efficiency in applications such as gene therapy and gene silencing has been clearly linked to the local, nano-scale organization of the nucleic acid in the vehicle, as well as to the global properties (e.g.

Bursting bubbles and bilayers.

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.

Bubble nucleation in lipid bilayers: a mechanism for low frequency ultrasound disruption.

Recent experiments have shown that low frequency ultrasound (LFUS) induces leakage from lipid vesicles. However, the mechanism by which LFUS disrupts the lipid bilayer structure is not clear. In this paper we develop a theoretical model to test the possibility that gas molecule partitioning from the aqueous media into the lipid bilayer core can lead to the nucleation of microscale gas bubbles.

Low-frequency ultrasound-induced transport across non-raft-forming ternary lipid bilayers.

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.

Effect of colloidal particle size on adsorbed monodisperse and bidisperse monolayers.

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.

Diffusion through colloidosome shells.

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.

Controlling surface porosity and release from hydrogels using a colloidal particle coating.

Recent studies suggest that coating microcapsules by a shell composed of impenetrable colloidal particles (thereby forming 'colloidosomes') can be used to control surface porosity, and therefore, permeability. The voids between the particles in the coating define the size of the surface pores available for transport. However, to date, data demonstrating this selectivity has been largely qualitative.

Phase-transition- and dissipation-driven budding in lipid vesicles.

Membrane budding has been extensively studied as an equilibrium process attributed to the formation of coexisting domains or changes in the vesicle area-to-volume ratio (reduced volume). In contrast, non-equilibrium budding remains experimentally widely unexplored, especially when timescales fall well below the characteristic diffusion time of lipids, tau. We show that localized mechanical perturbations, initiated by driving giant unilamellar vesicles (GUVs) through their lipid main phase transition from the gel to the fluid phase, lead to the immediate formation of rapidly growing, localized, non-equilibrium buds when the transition takes place at short timescales ( View Article and Find Full Text PDF

Coupling between line tension and domain contact angle in heterogeneous membranes.

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.

Line tension and coalescence in heterogeneous membranes.

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.

Colloidal assembly route for responsive colloidosomes with tunable permeability.

We present a robust and straightforward approach for fabricating a novel colloidosome system where colloidal particles are assembled to form colloidal shells on the surface of stimuli-responsive microgel scaffolds. We demonstrate that the structural properties of the colloidal shells can be controlled through the colloidal particle size and modulus, and the state of supporting microgel particles. This technique offers a new way to engineer colloidosomes, enabling fine control over their permeability over a wide range of length scales.

Lipid tail chain asymmetry and the strength of membrane-induced interactions between membrane proteins.

Many lipids are composed of asymmetric tail chains that differ by their molecular weight (MW) and/or degree of saturation. Previous studies found that membrane moduli vary with the degree of lipid tail asymmetry. However, to date little is known regarding the effect (if any) of tail asymmetry on the membrane-induced interactions between embedded proteins.

Effect of membrane microheterogeneity and domain size on fluorescence resonance energy transfer.

Studies of multicomponent membranes suggest lateral inhomogeneity in the form of membrane domains, but the size of small (nanoscale) domains in situ cannot be determined with current techniques. In this article, we present a model that enables extraction of membrane domain size from time-resolved fluorescence resonance energy transfer (FRET) data. We expand upon a classic approach to the infinite phase separation limit and formulate a model that accounts for the presence of disklike domains of finite dimensions within a two-dimensional infinite planar bilayer.

Determination of membrane domain size by fluorescence resonance energy transfer: effects of domain polydispersity and packing.

Fluorescence resonance energy transfer (FRET) is sensitive to lateral heterogeneity in multicomponent membranes. Recently, we developed a model that enables the extraction of domain size from time-resolved FRET data, and here we examine the effects of domain polydispersity and spatial ordering on the accuracy of domain size determination. The model is applied to Monte Carlo calculations of membranes containing polydisperse domains, either randomly or hexagonally packed for three probe-partitioning schemes and three domain surface coverages.

Effect of polymer characteristics on structure of polymer-liposome complexes.

In the current study, we examined the effect of polymer characteristics on the structure of complexes formed between poly(methacrylic acid-co-n-alkyl methacrylate) and with phosphatidylcholine/cholesterol liposomes. We varied the polymer concentration in the vesicles, the preparation concentration of lipid and polymer components during preparation, the molecular weight of the polymer chain, the molecular weight of the polymer's hydrophobic side groups and their mole fraction. The vesicle behavior indicated polymer-free bilayers and bilayers complexed with polymer coexisted at low polymer concentrations.

Pharmacokinetic and behavioral characterization of a long-term antipsychotic delivery system in rodents and rabbits.

Rationale: 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.

Objectives: The aim of this study was to provide biological proof of concept for a long-term implantable antipsychotic delivery system in rodents and rabbits.

Effect of mixing on the morphology of cylindrical micelles.

Increasing the spontaneous curvature of an amphiphile can lead to a first-order morphology transition from threadlike micelles to a branched network. The two morphologies were linked to entropy-driven topological defects; networks are dominated by Y-junctions, while linear threadlike structures are dominated by spherical end-caps. In this paper we investigate the effect of mixing on the morphological transitions in nonionic amphiphilic systems.

Effect of drug type on the degradation rate of PLGA matrices.

We compare the rate of drug release through the degradation of 50:50 polylactic-co-glycolic acid polymer pellets, for six different drugs: Thiothixene, Haloperidol, Hydrochlorothiozide, Corticosterone, Ibuprofen, and Aspirin. Despite using the same polymer matrix and drug loading (20% by weight), we find that the rate of polymer degradation and the drug release profile differ significantly between the drugs. We conclude that the design of biodegradable polymeric drug carriers with high drug loadings must account for the effect of the drug on the polymer degradation and drug release rate.

Dewetting instability during the formation of polymersomes from block-copolymer-stabilized double emulsions.

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.