Swelling kinetics of mixtures of soybean phosphatidylcholine and glycerol dioleate.

Lipid-based drug delivery systems offer the potential to enhance bioavailability, reduce dosing frequency, and improve patient adherence. In aqueous environment, initially dry lipid depots take up water and form liquid crystalline phases. Variation of lipid composition, depot size and hydration-induced phase transitions will plausibly affect the diffusion in and out of the depot.

Phase behavior of soybean phosphatidylcholine and glycerol dioleate in hydrated and dehydrated states studied by small-angle X-ray scattering.

Soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO) form liquid crystal nanostructures in aqueous environments, and their mixtures can effectively encapsulate active pharmaceutical ingredients (API). When used in a subcutaneous environment, the liquid crystalline matrix gradually hydrates and degrades in the tissue whilst slowly releasing the API. Hydration dependent SPC/GDO phase behavior is complex, non-trivial, and still not fully understood.

Immobilisation of β-galactosidase within a lipid sponge phase: structure, stability and kinetics characterisation.

In the formulation of an active enzyme enclosed in a matrix for controlled delivery, it is a challenge to achieve a high protein load and to ensure high activity of the protein. For the first time to our knowledge, we report the use of a highly swollen lipid sponge (L) phase for encapsulation of the large active enzyme, β-galactosidase (β-gal, 238 kDa). This enzyme has large relevance for applications in, e.

Encapsulation of Aspartic Protease in Nonlamellar Lipid Liquid Crystalline Phases.

Encapsulation of proteins within lipid inverse bicontinuous cubic phases (Q) has been widely studied for many applications, such as protein crystallization or drug delivery of proteins for food and pharmaceutical purposes. However, the use of the lipid sponge (L) phase for encapsulation of proteins has not yet been well explored. Here, we have employed a lipid system that forms highly swollen sponge phases to entrap aspartic protease (34 kDa), an enzyme used for food processing, e.

On the Molecular Interactions in Lipid Bilayer-Water Assemblies of Different Curvatures.

This work concerns the importance of intermolecular interactions present in aqueous lipid assembly systems depending on the type of aggregates they form. We have studied aqueous mixtures of diglycerol monooleate, Capmul glycerol monoleate (GMO-50) and polyoxyethylene (20) sorbitan monooleate (Polysorbate 80, P80) using small-angle X-ray scattering (SAXS) measurements to reveal the structure of liquid crystalline phases. On the basis of the SAXS data, a phase diagram was constructed.

Interfacial properties of lipid sponge-like nanoparticles and the role of stabilizer on particle structure and surface interactions.

The advantage of using nonlamellar lipid liquid crystalline phases has been demonstrated in many applications, such as drug delivery, protein encapsulation and crystallisation. We have recently reported that a mixture of mono- and diglycerides is able to form sponge-like nanoparticles (L3-NPs) with large enough aqueous pores to encapsulate macromolecules such as proteins. Here we use small angle neutron scattering (SANS) to reveal morphology, structural and chemical composition of these polysorbate 80 (P80) stabilized sponge phase nanoparticles, not previously known.

The lipolytic degradation of highly structured cubic micellar nanoparticles of soy phosphatidylcholine and glycerol dioleate by phospholipase A and triacylglycerol lipase.

The effects of different lipolytic enzymes on the structure of lipid liquid crystalline nano-particles (LCNP) have been investigated by cryogenic transmission electron microscopy (cryo-TEM) and synchrotron small angle X-ray diffraction (SAXD). Here we used highly structured cubic micellar (Fd3m) nanoparticles of 50/50 (wt%/wt%) soy phosphatidyl choline (SPC)/glycerol dioleate (GDO) as substrate. Two types of lipolytic enzymes were used, phospholipase A (PLA) that catalyses degradation of the phospholipid component, SPC, and porcine pancreatic triacylglycerol lipase (TGL) that facilitate the hydrolysis of the diglyceride, GDO.

Relationship between Structure and Fluctuations of Lipid Nonlamellar Phases Deposited at the Solid-Liquid Interface.

The structure and dynamics of nanostructure films formed by mixtures of soy phosphatidylcholine and glycerol dioleate at the silicon-aqueous interface were studied by grazing incidence neutron spin echo spectroscopy (GINSES), specular and off-specular neutron reflectometry, and small-angle X-ray diffraction. Reverse hexagonal (H) and micellar cubic phase (Fd3m) layers at the solid-liquid interface have been identified with neutron reflectometry measurements. A preferred orientation of the liquid crystalline (LC) domains was observed only for the anisotropic H phase.

Interfacial properties of POPC/GDO liquid crystalline nanoparticles deposited on anionic and cationic silica surfaces.

Reversed lipid liquid crystalline nanoparticles (LCNPs) of the cubic micellar (I) phase have high potential in drug delivery applications due to their ability to encapsulate both hydrophobic and hydrophilic drug molecules. Their interactions with various interfaces, and the consequences for the particle structure and integrity, are essential considerations in their effectiveness as drug delivery vehicles. Here, we have studied LCNPs formed of equal fractions of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and glycerol dioleate in the presence of different fractions of the stabilizer Polysorbate 80.

Sponge Phases and Nanoparticle Dispersions in Aqueous Mixtures of Mono- and Diglycerides.

The lipid liquid crystalline sponge phase (L3) has the advantages that it is a nanoscopically bicontinuous bilayer network able to accommodate large amounts of water and it is easy to manipulate due to its fluidity. This paper reports on the detailed characterization of L3 phases with water channels large enough to encapsulate bioactive macromolecules such as proteins. The aqueous phase behavior of a novel lipid mixture system, consisting of diglycerol monooleate (DGMO), and a mixture of mono-, di- and triglycerides (Capmul GMO-50) was studied.

Thermomyces lanuginosus lipase-catalyzed hydrolysis of the lipid cubic liquid crystalline nanoparticles.

In this study well-ordered glycerol monooleate (GMO)-based cubic liquid crystalline nanoparticles (LCNPs) have been used as substrates for Thermomyces lanuginosus lipase in order to establish the relation between the catalytic activity, measured by pH-stat titration, and the change in morphology and nanostructure determined by cryogenic transmission electron microscopy and synchrotron small angle X-ray diffraction. The initial lipase catalyzed LCNP hydrolysis rate is approximately 25% higher for large 350nm nanoparticles compared to the small 190nm particles, which is attributed to the increased number of structural defects on the particle surface. At pH 8.

Structural effects of the dispersing agent polysorbate 80 on liquid crystalline nanoparticles of soy phosphatidylcholine and glycerol dioleate.

Well-defined, stable and highly structured I2 (Fd3̅m) liquid crystalline nanoparticles (LCNP) of 50/50 (wt/wt) soy phosphatidylcholine (SPC)/glycerol dioleate (GDO), can be formed by using a low fraction (5-10 wt%) of the dispersing polymeric surfactant polyoxyethylene (20) sorbitan monooleate (polysorbate 80 or P80). In the present study we used small angle neutron scattering (SANS) and deuterated P80 (d-P80) to determine the location and concentration of P80 within the LCNP and small angle X-ray scattering (SAXS) to reveal the internal structure. SANS data suggests that some d-P80 already penetrates the particle core at 5%.

Non-lamellar lipid liquid crystalline structures at interfaces.

The self-assembly of lipids leads to the formation of a rich variety of nano-structures, not only restricted to lipid bilayers, but also encompassing non-lamellar liquid crystalline structures, such as cubic, hexagonal, and sponge phases. These non-lamellar phases have been increasingly recognized as important for living systems, both in terms of providing compartmentalization and as regulators of biological activity. Consequently, they are of great interest for their potential as delivery systems in pharmaceutical, food and cosmetic applications.

Formation of highly structured cubic micellar lipid nanoparticles of soy phosphatidylcholine and glycerol dioleate and their degradation by triacylglycerol lipase.

Lipid nanoparticles of reversed internal phase structures, such as cubic micellar (I2) structure show good drug loading ability of peptides and proteins as well as some small molecules. Due to their controllable small size and inner morphology, such nanoparticles are suitable for drug delivery using several different administration routes, including intravenous, intramuscular, and subcutaneous injection. A very interesting system in this regard, is the two component soy phosphatidylcholine (SPC)/glycerol dioleate (GDO) system, which depending on the ratio of the lipid components form a range of reversed liquid crystalline phases.

Bioadhesive lipid compositions: self-assembly structures, functionality, and medical applications.

Lipid-based liquid crystalline compositions of phospholipids and diglycerides have unique bioadhesive properties with several medical applications, as exemplified by a lipid-based medical device indicated for management and relief of intraoral pain. The present paper describes the relation between self-assembly properties of phosphatidyl choline (PC) and glycerol dioleate (GDO) mixtures in the presence of aqueous fluids and functional attributes of the system, including: film formation and bioadhesion, intraoral coverage, acceptance by patients, and potential as a drug delivery system. The phase behavior of PC/GDO was characterized using synchrotron small-angle X-ray scattering.

Hydration of lysozyme studied by Raman spectroscopy.

Hydration plays a fundamental role in maintaining the three-dimensional structure and function of proteins. In this study, Raman spectroscopy was used to probe the hydration induced structural changes at various sites of lysozyme under isothermal conditions in the range of water contents from 0 to 44 wt %. Raman hydration curves were constructed from detailed analysis of marker bands.

Adsorption of lipid liquid crystalline nanoparticles: effects of particle composition, internal structure, and phase behavior.

Controlling the interfacial behavior and properties of lipid liquid crystalline nanoparticles (LCNPs) at surfaces is essential for their application for preparing functional surface coatings as well as understanding some aspects of their properties as drug delivery vehicles. Here we have studied a LCNP system formed by mixing soy phosphatidylcholine (SPC), forming liquid crystalline lamellar structures in excess water, and glycerol dioleate (GDO), forming reversed structures, dispersed into nanoparticle with the surfactant polysorbate 80 (P80) as stabilizer. LCNP particle properties were controlled by using different ratios of the lipid building blocks as well as different concentrations of the surfactant P80.

Horse heart cytochrome c entrapped into the hydrated liquid-crystalline phases of phytantriol: X-ray diffraction and Raman spectroscopic characterization.

Small angle X-ray diffraction (SAXD), resonance Raman (RR) spectroscopy with 413 nm excitation, and non-resonance Raman technique with 785 nm excitation were used to probe the influence of entrapped cytochrome c (Cyt c) on the structure of hydrated phytantriol (Phyt) liquid-crystalline phases as well as conformational changes of heme group and secondary structure of the protein. SAXD measurements indicated that incorporation of Cyt c affects both nanostructure dimensions and type of liquid-crystalline phases of hydrated Phyt. The unit cell dimensions decrease with increasing Cyt c concentration for all phases.

Adsorption of lipid liquid crystalline nanoparticles on cationic, hydrophilic, and hydrophobic surfaces.

Investigation of nonlamellar nanoparticles formed by dispersion of self-assembled lipid liquid crystalline phases is stimulated by their many potential applications in science and technology; resulting from their unique solubilizing, encapsulating, and space-dividing nature. Understanding the interfacial behavior of lipid liquid crystalline nanoparticles (LCNPs) at surfaces can facilitate the exploitation of such systems for a number of potentially interesting uses, including preparation of functional surface coatings and uses as carriers of biologically active substances. We have studied the adsorption of LCNP, based on phosphatidylcholine/glycerol dioleate and Polysorbate 80 as stabilizers, at different model surfaces by use of in situ ellipsometry.

Enzymatic activity of lipase-nanoparticle conjugates and the digestion of lipid liquid crystalline assemblies.

Variants of lipase were attached to gold nanoparticles (NPs) and their enzymatic activity was studied. The two bioengineered lipase variants have been prepared with biotin groups attached to different residues on the protein outer surface. The biotinylation was evidenced by denaturing polyacrylamide gel electrophoresis and quantified by the ([2-(4'-hydroxyazobenzene)]benzoic acid spectrophotometric test.

Emulsions-directed assembly of gold nanoparticles to molecularly-linked and size-controlled spherical aggregates.

Aggregation of gold nanoparticles into soluble spherical assemblies using bi-functional ligands i.e., dithiols has recently been demonstrated but with limited control over the size of such assemblies.

Interactions of lipid-based liquid crystalline nanoparticles with model and cell membranes.

Lipid-based liquid crystalline nanoparticles (LCNPs) are interesting candidates for drug delivery applications, for instance as solubilizing or encapsulating carriers for intravenous (i.v.) drugs.

Interaction between lamellar (vesicles) and nonlamellar lipid liquid-crystalline nanoparticles as studied by time-resolved small-angle X-ray diffraction.

The kinetics of structure change when dispersions of two different types of lipid-based liquid-crystalline phases, one lamellar and one reversed, are mixed has been investigated using synchrotron small-angle X-ray diffraction and ellipsometry. The systems studied were (i) cubic-phase nanoparticles (CPNPs) based on glycerol monooleate (GMO) stabilized with a nonionic block copolymer, Pluronic F-127; (ii) CPNPs based on phytantriol (PtOH) stabilized with D-alpha-Tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS); and (iii) hexagonal-phase nanoparticles (HPNPs) based on a lipid mixture of diglycerol monooleate/glycerol dioleate, stabilized by Pluronic F-127. Time-resolved small-angle X-ray diffraction was used to track structural changes within nonlamellar nanoparticles when they interact with uni- and multilamellar vesicles of dioleoylphosphatidylcholine and dipalmitoylphatidylcholine.

Controlled step growth of molecularly linked gold nanoparticles: from metallic monomers to dimers to polymeric nanoparticle chains.

The solution-phase assembly of 15 nm gold particles into relatively linear chains of fairly controllable length of up to 1 mum is achieved by molecularly linking nanoparticles with alkanedithiols. This step-growth process can be controlled to prepare dimers, oligomers, and polymer-like gold nanoparticle chains by varying the ratio of alkanedithiols to nanoparticles. These size-controlled, relatively linear aggregates remain suspended in ethanol solution without precipitation for several weeks to months depending on the chain length.