Fredrik Tiberg

Ellipsometry Studies of the Self-Assembly of Nonionic Surfactants at the Silica-Water Interface: Equilibrium Aspects

The nature of layers of a series of poly(ethy1ene glycol) monoalkyl ethers (C,,Em) adsorbed on silica surfaces has been systematically investigated by means of null ellipsometry. The results show that adsorption remains low until a well-defined concentration ((=0.6-0.9)cmc) is exceeded. Then, as surfactants in the interfacial region start to self-absemble, it increases abruptly and plateau adsorption is generally observed prior to the cmc. The normal extension of the interfacial aggregates is relatively constant from intermediate to high surface coverage. Increasing the ethylene oxide to hydrocarbon ratio results in a decreased adsorption. The mean optical thickness, on the other hand, is relatively independent of the number of ethylene oxide groups in the surfactant but almost linearly dependent on the length of the hydrocarbon tail. The values obtained for these parameters suggest that the adsorbed layer is built up of discrete surface aggregates, or micelles, with dimensions resembling those observed in bulk solution. A more refined optical model of the adsorbed layer confirms the notion of surface micelles growing with increasing hydrocarbon content. It also points out that the extension of the surface micelles is slightly larger than the measured mean optical thickness. In addition to studies of neat C S , surfactants, we also examine the adsorption of mixed surfactant systems. Changes observed in adsorption on altering the bulk ratio of two surfactants are well correlated to the bulk micellar surfactant ratio calculated by ideal solution theory.

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. Here it is important that the carriers are safe and tolerable and do not have, e.g. hemolytic activity. In the present study we have studied LCNP particles of different compositions with respect to their mixing behavior and membrane destabilizing effects in model and cell membrane systems. Different types of non-lamellar LCNPs were studied including cubic phase nanoparticles (Cubosome) based on glycerol monooleate (GMO), hexagonal phase nanoparticles (Hexosome) based on diglycerol monooleate (DGMO) and glycerol dioleate (GDO), sponge phase nanoparticles based on DGMO/GDO/polysorbate 80 (P80) and non-lamellar nanoparticles based on soy phosphatidylcholine (SPC)/GDO. Importantly, the LCNPs based on the long-chain monoacyl lipid, GMO, were shown to display a very fast and complete lipid mixing with model membranes composed of multilamellar SPC liposomes as assessed by a fluorescence energy transfer (FRET) assay. The result correlated well with pronounced hemolytic properties observed when the GMO-based LCNPs were mixed with rat whole blood. In sharp contrast, LCNPs based on mixtures of the long-chain diacyl lipids, SPC and GDO, were found to be practically inert towards both hemolysis in rat whole blood as well as lipid mixing with SPC model membranes. The LCNP dispersions based on a mixture of long-chain monoacyl and diacyl lipids, DGMO/GDO, displayed an intermediate behavior compared to the GMO and SPC/GDO-based systems with respect to both hemolysis and lipid mixing. It is concluded that GMO-based LCNPs are unsuitable for parenteral drug delivery applications (e.g. i.v. administration) while the SPC/GDO-based LCNPs exhibit good properties with limited lipid mixing and hemolytic activity. The correlation between results from lipid mixing or FRET experiments and the in vitro hemolysis data indicates that FRET assays can be one useful screening tool for parenteral drug delivery systems. It is argued that the hemolytic potential is correlated with chemical activity of the monomers in the mixtures.

Adsorption and surface-induced self-assembly of surfactants at the solid)aqueous interface

Increasing insight into the interfacial behaviour of surfactants has emerged during the past few years. Important advances in this area are largely due to the use of surface-specific techniques like ellipsometry, neutron reflectivity, fluorescence spectroscopy, and atomic force microscopy (AFM) for in situ studies of surfactant layer properties. This review covers recent developments in the area which have contributed to the current understanding of adsorption mechanisms and interfacial structures.

Effects on protein adsorption, bacterial adhesion and contact angle of grafting PEG chains to polystyrene

Poly(ethylene glycol) (PEG) has been grafted to polystyrene using branched poly(ethylene imine) (PEI) as an anchoring polymer. A dense grafting of PEG chains is obtained if a PEG-PEI adduct is first prepared by treatment of PEI with PEG epoxide and the adduct subsequently adsorbed on an oxidized polystyrene surface. Prepared in this way, the PEG-PEI adduct is irreversibly attached to the surface with the PEG chains oriented towards the aqueous phase, as shown by ellipsometry. This dense PEG coating is highly effective in preventing adsorption of fibrinogen and IgG, as well as adhesion of the oral bacterium Streptococcus mutans. Somewhat surprisingly, the degree of PEG branching, as well as the PEG molecular weight, did not markedly influence protein repelling properties. The water contact angle on polystyrene decreased in the order: untreated polystyrene > oxidized > PEI treated > PEG-PEI treated. Block copolymers of poly(ethylene glycol)/poly(propylene glycol) type attached to polystyrene showed temperat...

Grafting with hydrophilic polymer chains to prepare protein-resistant surfaces

Abstract Different ways of grafting poly(ethylene glycol) (PEG) chains to solid polyethylene were compared with respect to grafting density and efficiency in preventing fibrinogen adsorption. Covalent grafting of PEG was performed by attaching a nucleophilic PEG derivative to electrophilic surface groups or by binding electrophilic PEG to nucleophilic groups at the solid surface. Two adsorption procedures were also used. In the first of these an ethylene oxide propylene oxide (EO-PO) block copolymer was adsorbed at unmodified, hydrophobic polyethylene. In the second procedure the surface was made car☐yl-functional by free-radical grafting of tiglic acid and then exposed to a solution of a positively charged copolymer consisting of PEG chains grafted to poly(ethylene imine) (PEI). According to ESCA measurements, all four routes gave proper PEG grafting densities and the difference in the ration of C C O carbon (from PEG) to C C C carbon (from the underlying surface) was relatively small. There was a substantial difference in efficiency in fibrinogen rejection, however. Whereas surface modification with the PEG-PEI graft copolymer gave the lowest, treatment with the EO-PO block copolymer gave the highest amount of protein adsorption. The good effect of the PEG-PEI layer is believed to be related to the large entropy loss associated with protein adsorption on top of this copolymer which is known to be loosely bound in a loops-and-trains configuration. The limited effect of the EO-PO block copolymer may be due to the fact that this polymer is not entirely hydrophilic at the temperature used. Another contributing factor may be that the EO-PO block copolymer, unlike the PEG-PEI graft copolymer, is not irreversibly bound to the surface and may therefore be exchanged by fibrinogen.

Spreading dynamics of liquids and surfactant solutions on partially wettable hydrophobic substrates

Abstract The drop spreading of water and aqueous solutions of ethanol and nonionic surfactant on hydrophobic substrates (alkylsilane treated glass) have been investigated. For the low viscous liquids and solutions, the spreading on the surface of hydrophobic glass rod was also studied and compared to the drop spreading experiment. In both experiments, care was taken to ensure a minimum impact of inertial forces. The results for the aqueous systems show rapid initial spreading processes that abruptly halts after less than 30 ms, as the interfacial tension forces are balanced. In the case of surfactants solutions, this is followed by slower adsorption driven drift towards equilibrium conditions. During the initial spreading phase, the wetting front exhibits ∼t1/2 spreading law. Two more viscous liquids, ethylene glycol and glycerol, were also examined and found to show a weaker time-dependence in the whole spreading regime. An ∼t1/10 scaling of the drop radius versus time was for these liquids observed in the asymptotic long-time regime. For the surfactant solution, a slow relaxation towards equilibrium was observed following the initial fast spreading phase. The rate-limiting process in this regimes was in the drop spreading experiment found to be surfactant adsorption from the bulk to the expanding liquid–vapour interface, whereas surface diffusion at the liquid–vapour interface appeared rate-determining in the rod experiment. The reason for this is the differences in aspect ratio between relative expansion of the liquid–vapour and solid–liquid interfaces during spreading in the two experiments. In the study of surfactant solution spreading, the importance of surface relaxation prior to contact of the solution and the solid was also pointed out.

A combined in vitro and in vivo study on the interactions between somatostatin and lipid-based liquid crystalline drug carriers and bilayers

Somatostatin (SST) is a peptide hormone active in the regulation of the endocrine system via different somatostatin receptors subtypes. It inhibits the release of multiple secondary peptide hormones, affecting neurotransmission and cell proliferation. SST has a high therapeutic potential in the treatment of disease, such as acromegali, acute pancreatitis and gastroenteropathic endocrine tumors. However, its practical use is hampered by a short in vivo half-life of only a few minutes in man. For this reason more long-lived SST analogues, including octreotide and lanreotide, have been developed. Here we have used native SST as a model compound for a different approach of extending plasma half-lives of in vivo labile biomolecules. Through association of the peptide hormone with lipid-based liquid crystalline nanoparticle (LCNP) carriers, the terminal half-life of SST injected intravenously in rats is shown to be significantly extended from less than 10min to more than 1h. The effect on the in vivo circulation behavior depends on the mode of peptide association to the lipid particles and related physicochemical properties are discussed on the basis of in vitro light scattering, z-potential and adsorption measurements. It is concluded that application of the LCNP delivery system represents an interesting alternative to chemical modifications of in vivo sensitive therapeutically interesting peptides.

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. For a 50/50 (w/w) ratio in excess water, these lipids have been shown to form a reversed cubic micellar (I2) phase of the Fd3m structure. Here, we demonstrate that this SPC/GDO phase, in the presence of small quantities (5-10 wt %) of Polysorbate 80 (P80), can be dispersed into nanoparticles, still with well-defined Fd3m structure. The resulting nanoparticle dispersion has a narrow size distribution and exhibit good long-term stability. In pharmaceutical applications, biodegradation pathways of the drug delivery vehicles and their components are important considerations. In the second part of the study we show how the structure of the particles evolves during exposure to a triacylglycerol lipase (TGL) under physiological-like temperature and pH. TGL catalyzes the lipolytic degradation of acylglycerides, such as GDO, to monoglycerides, glycerol, and free fatty acids. During the degradation, the interior phase of the particles is shown to undergo continuous phase transitions from the reversed I2 structure to structures of less negative curvature (2D hexagonal, bicontinuous cubic, and sponge), ultimately resulting in the formation of multilamellar vesicles.

Using poly(ethylene imine) to graft poly(ethylene glycol) or polysaccharide to polystyrene

Abstract A novel method of grafting poly(ethylene glycol) (PEG) or polysaccharide to polystyrene has been developed. The non-charged, hydrophilic polymer is firstly grafted to poly(ethylene imine). After prior oxidation of the solid surface, the graft copolymer is subsequently adsorbed. Analysis by electron spectroscopy for chemical analysis and ellipsometry indicates a trains-and-loops arrangement of the copolymer on the surface with densely packed PEG or polysaccharide chains oriented towards the bulk water phase. Ellipsometry also shows that whereas the PEG grafting is fast, the polysaccharide grafting is more sluggish. Attachment of both graft copolymers is completely irreversible, as seen also by ellipsometry. The surfaces obtained are highly protein repellent, as shown by enzyme-linked immunosorbent assay using fibrinogen and immunoglobulin G as model proteins.

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. The technique allows time-resolved monitoring of the layer thickness and the amount adsorbed, thereby providing insights into the restructuring of the lipid nanoparticle upon adsorption. The effects of solvent condition, electrolyte concentration, particle size, and surface chemistry on adsorbed layer properties were investigated. Furthermore, the internal structures of the particles were investigated by cryo-transmission electron microscopy and small angle X-ray diffraction on the corresponding liquid crystalline phases in excess water. LCNPs are shown to form well-defined layers at the solid-liquid interface with a structure and coverage that are determined by the interplay between the self-assembly properties of the lipids and lipid surface interactions, respectively. At the hydrophobic surface, hydrophobic interaction results in a structural transition from the original LCNP morphology to a monolayer structure at the interface. In contrast, at cationic and hydrophilic surfaces, relaxation is a relatively slow process, resulting in much thicker adsorbed layers, with thickness and adsorption behavior that to a greater extent reflect the original bulk LCNP properties.