Acid-triggered transformation of diortho ester phosphocholine liposome

The use of pH-sensitive liposomes for acid-triggered site-specific drug delivery is one of the more promising approaches to improve the therapeutic index of drugs. Here, we report the synthesis, assembly, and hydrolysis of the first ortho ester phosphocholine (OEPC). The acid hydrolysis of OEPC liposomes consists of a lag phase and a burst phase. The lag time is pH-dependent-the lower the pH, the shorter the time. Upon acid hydrolysis, the OEPC liposomes were transformed into leaky metastable vesicles that rapidly collapsed in the presence of albumin. OEPC, when formulated with cationic lipid, significantly enhanced the transfection efficiency compared with that of the pH-insensitive formulation.     

High-throughput transformation of colloidal polymer spheres to discs simply via magnetic stirring of their dispersions

In this article, we have successfully demonstrated the high-throughput production of colloidal discs via magnetic stirring of aqueous dispersions of monodisperse, sulfate-stabilized polystyrene (PS) spheres in the presence of a good organic solvent. The organic solvent could be water-miscible, such as tetrahydrofuran, or water-immiscible, such as chloroform. Water-immiscible organic solvents were mixed into aqueous dispersions of PS spheres in the presence of sodium dodecyl sulfate. The geometry of the resulting discs could be easily adjusted by the magnetic stirring time and speed, the stirring bar weight, and the amount of organic solvent. Our strategy is simple, scalable, and hardly dependent on the nature of the organic solvent and the PS sphere diameter; PS spheres with diameters ranging from 200 nm to 5 μm were deformed into discs with almost 100% yield. When organic solutions of fluorescent dyes and nanoparticles were used instead of pure organic solvents for PS sphere liquefaction, fluorescent discs were obtained, underlining the effective, efficient encapsulation of the fluorescent substance in the discs.     

Preparation and properties of colloidal iron dispersions

We systematically study the properties of dispersions of iron-based colloids synthesized in a broad size range by thermal decomposition of ironcarbonyl using different stabilizing surfactants. The synthesis results in stable dispersions of monodomain magnetic colloids. Our particles appear to consist of an amorphous Fe(0.75)C(0.25) alloy. Sizes of particles coated with modified polyisobutene or oleic acid can be easily controlled in the 2-10 nm range by varying the amounts of reactants. Extensive characterization with various techniques gives particle sizes that agree well with each other. In contrast to dispersions of small particles, which consist of single colloids, dynamic aggregates are present in dispersions of larger particles. On exposure to air, an oxide layer forms on the particle surface, consisting of a disordered Fe(III) oxide.     

Interactions between local anesthetics and lipid dispersions studied with liposome electrokinetic capillary chromatography

In the case of local anesthetic intoxication, intravenous administration of lipid-based Intralipid dispersion (Fresenius Kabi) can be used for the entrapment of hydrophobic drugs. Our long-term aim is to develop a sensitive, efficient, and non-harmful lipid-based formulation to specifically trap harmful substances. In this study liposome electrokinetic capillary chromatography (LEKC) was used to study the interactions between local anesthetics and Intralipid or liposome dispersions. Intralipid dispersion and extruded liposomes with different concentrations of 1-palmitoyl-2-oleyl-sn-glycerophosphatidylcholine (POPC), phosphatidylglycerol, cardiolipin, cholesterol, oleic acid, and linoleic acid were used as a pseudostationary phase in LEKC and their interactions with lidocaine, prilocaine, and bupivacaine were studied. POPC liposomes containing 1 mol% of palmitoyl-2-[12-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecanoyl]-sn-glycero-3-phosphocholine as a fluorescent marker were used for the first time in LEKC connected with laser-induced fluorescent detection in order to calculate the retention factor for anesthetics.     

Preparation of reactive block copolymers and their transformation to hollowed nanostructures

A novel polymeric hollow nanostructure was generated using micellar template method through a three‐step procedure. First, the block copolymers were synthesized via ring‐opening metathesis polymerization by sequentially adding monomers 7‐oxanorborn‐5‐ene‐exo‐exo‐2,3‐dicarboxylic acid dimethyl ester and the mixture of norbornene and 2,3‐bis(2‐bromoisobutyryloxymethyl)‐5‐norbornene in chloroform, and also atom transfer radical polymerization of 4‐(3‐butenyl)styrene was carried out by using the as‐obtained block copolymer poly(7‐oxanorborn‐5‐ene‐exo,exo‐2,3‐dicarboxylic acid dimethylester)‐block‐poly(norbornene‐co‐2,3‐bis(2‐bromoisobutyryloxymethyl)‐5‐norbornene as macroinitiator to afford a graft copolymer bearing poly(4‐(3‐butenyl)styrene) branch poly(7‐oxanorborn‐5‐ene‐exo,exo‐2,3‐dicarboxylic acid dimethylester)‐block‐poly(norbornene‐co‐2,3‐bis(2‐bromoisobutyryloxymethyl)‐5‐norbornene)‐graft‐poly(4‐(3‐butenyl)styrene). Second, the shell‐crosslinked micelles were prepared by ruthenium‐mediated ring‐closing metathesis of poly(4‐(3‐butenyl)styrene) branches in intramicelle formed from the copolymers self‐assembly spontaneously in toluene. Finally, the hollowed spherical nanoparticles were presented by removing the micellar copolymer backbone through the cleavage of the ester bonds away from the crosslinked network of branches. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Preparation of aqueous dispersions of paraffin and ceresin

The process of preparing aqueous dispersions of solid petroleum hydrocarbons was studied. Stable aqueous dispersions of petroleum paraffin can be prepared using polyvinyl alcohol in combination with a hydrotropic additive as a stabilizer. While for stabilization of dispersion of ceresin, which is a microcrystalline wax, it is necessary to use an anionic surfactant.     

Preparation and characterization of multilayered polymer nanotube dispersions

Despite considerable efforts to synthesize nanotubes using porous alumina or polycarbonate membrane templates, few studies have addressed the resulting nanotube dispersion. We prepared dispersions of multilayered polyethylenimine/maleic anhydride alternating copolymer (PEI/MAAC) nanotubes synthesized with porous alumina templates. After mechanical polishing to remove the residual polymer surface layer from templates and subsequent template dissolution, the multilayered PEI/MAAC nanotubes were easily dispersed in water at neutral pH by polyelectrolyte adsorption, producing nanotube dispersions that were stable for at least 3 months. We characterized the dispersions using phase-contrast optical microscopy, electro-optics, electrophoresis, and viscometry to help understand their colloidal properties in the dilute and semidilute regimes. The dispersions were resistant to salt-induced aggregation up to at least 1 mM NaCl and were optically anisotropic when subjected to an electric field or flow. Interestingly, the electrophoretic mobility of polystyrene sulfonate (PSS)-stabilized nanotubes increases with increasing ionic strength, because of the high surface charge and softness of the adsorbed polyelectrolyte. Furthermore, unlike many rod-like colloid systems, the polymer nanotube dispersion has low viscosity because of weak rotary Brownian motions and strong tendency to shear thinning. At the high shear rates achieved in capillary viscometry experiments, however, we observed a slight shear thickening, which can be attributed to transient hydrocluster formation.     

Preparation of microlatex dispersions using oil-in-water microemulsions

The preparation of microlatex dispersions from microemulsions of a monomer (styrene, methylmethacrylate or vinyl acetate) is described. A simple method for preparing the microemulsion has been devised. This consists of forming a water-in-oil (w/o) emulsion using a low (HLB) surfactant (nonylphenol with 5, 6 or 7 moles ethylene oxide) and then titrating with an aqueous solution of a high HLB surfactant (nonylphenol with 15 or 16 moles ethylene oxide). A small amount of anionic surfactant (sodium lauryl sulphate, sodium dodecyl benzene sulphonate or dioctyl sulphosuccinate) was also incorporated to enhance the stability of the w/o emulsion and facilitate the inversion to an o/w microemulsion. The droplet-size distribution of the resulting microemulsion was determined using photon-correlation spectroscopy.Three different methods of polymerising the microemulsion were used. These were thermally induced polymerisation using potassium persulphate, azobis-2-methyl propamidinium dichloride (AMP-water-soluble initiators) or azobisisobutyronitrile (AIBN, an oil-soluble initiator). All these initiators required heating to 60°C, i.e. above the stability temperature of the microemulsion. In this case, the microlatices produced were fairly large (37–100 nm diameter) and had a broad particle-size distribution. The second polymerisation procedure was chemically induced using a redox system of hydrogen peroxide and ascorbic acid. This produced microlatices with small sizes (18–24 nm diameter) having a narrow-size distribution. The microlatex size was roughly two to three times the size of the microemulsion droplets. This showed that collision between two or three microemulsion droplets resulted in their coalescence during the polymerisation process. The third method of polymerisation was based on UV irradiation in conjunction with K₂S₂O₈, AMP or AIBN initiators. In this case, the microlatex size was also small (30–63 nm) with a narrow particle-size distribution.Microlatex particles were also prepared using a mixture of monomers (styrene plus methylmethacrylate) or mixture of monomers and a macromonomer, namely methoxy (polyethylene glycol)methacrylate. The latter was used to produce hairy particles, i.e. with grafted polyethylene oxide (PEO) chains.The stability of the microlatices was determined by adding electrolytes (NaCl, CaCl₂, Na₂SO₄ or MgSO₄) to determine the critical flocculation concentration (CFC). The nonionic latices were very stable giving no flocculation up to 6 mol dm^–3 NaCl or CaCl₂ and a CFC of 0.6 mol dm^–3 for Na₂SO₄ or MgSO₄. Charged latices were less stable than the nonionic ones. The critical flocculation temperatures (CFT) of all latices were determined as a function of electrolyte concentration. With the nonionic latices, CFC was higher than the -temperature for polyethylene oxide at the given electrolyte concentration. This indicated enhanced steric stabilisation as a result of the dense packing of the chains and hence an elastic contribution to the steric interaction. This was not the case with the charged latex, which showed CFT values lower than the -temperature. The hairy latices [i.e. those containing methoxy polyethylene glycol (PEG) methacrylate] were also less stable towards electrolyte (CFT was much lower than -temperature), indicating a low density of PEO layers.     

Preparation of polyurethane dispersions by miniemulsion polymerization

With a two‐step miniemulsion polymerization, hydrophobic polyurethane (PU) dispersions were prepared with a cosurfactant, the costabilizer hexadecane (HD) in the oil phase, and sodium dodecyl sulfate (SDS) in the water phase. The first step involved the formation of NCO‐terminated prepolymers between isophorone diisocyanate and poly(propylene glycol) oligomer in toluene. Next, PU dispersions were produced by a miniemulsion method in which an oil phase containing NCO‐terminated prepolymers, HD, the chain extender 1,4‐butanediol (BD), the crosslinking agent trimethylol propane (TMP), and the catalyst dibutyltin dilaurate was dispersed in the water phase containing SDS. The influence of experimental parameters, such as the ultrasonication time, concentrations of SDS and HD, and TMP/BD and NCO/OH equivalent ratios, on the sizes of the miniemulsion droplets and polymer particles, as well as the molecular weights and thermal properties of the PU polymer, was examined. The chemical structure of the produced PU polymer was identified with a Fourier transform infrared spectrometer. The molecular weight distribution and average particle size were measured through gel permeation chromatography and dynamic light scattering, respectively. The thermal stability of the PU polymer was characterized with thermogravimetric analysis. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4870–4881, 2005     

Dynamic processes in endocytic transformation of a raft-exhibiting giant liposome

The dynamic response of a raft-exhibiting giant liposome to external stimuli, such as the addition of Triton X-100 or osmotic stress, was studied. We observed that daughter vesicles are generated inside of the liposome through endocytic budding. It was found that the budding to generate daughter vesicles is classified into two different routes, simple budding through the invagination of a whole raft and budding from the boundary of a raft accompanied by waving motion. Smaller rafts show a preference for simple budding, whereas large rafts mainly adopt the other process. We discuss the mechanism of this difference in terms of the kinetic pathway of internalization by considering the line energy and bending energy of the membrane.     

Template-directed synthesis of silica-coated J-aggregate nanotapes

Self-assembly of porphyrin nanotapes in the presence of alkoxysilane reaction solutions produces hybrid nanofilaments consisting of an optically responsive J-aggregate core encased within an ultrathin shell of amorphous silica.     

Lyotropic liquid crystals and their dispersions relevant in foods

Major recent advancesNumerous reports during recent years concern colloidal dispersions of inverse lipid-water phases. Particles of the bicontinuous cubic phase appear to be the most important ones with regard to application possibilities, involving encapsulation of enzymes with stabilization of their native structures. New lipids have been found, which are able to form nanoparticle dispersions relevant to foods. Of particular interest is the incorporation of amphiphilic polymers in precursor types of lipid-water phases, resulting in spontanous formation of colloidal nanoparticle dispersions at exposure to an aqueous environment.     

The surface properties of phospholipid liposome systems and their characterisation

The field of liposome (vesicle) research has expanded considerably over the last 30 years. In physical chemical terms liposomes have many of the characteristics of colloidal particles and their stability is determined in part by the classical surface forces. It is now possible to engineer a wide range of liposomes varying in size, phospholipid composition and surface characteristics. The surfaces of liposomes can be modified by the choice of bilayer lipid as well as by the incorporation and covalent linkage of proteins (e.g. antibodies and sugar binding proteins [lectins]), glycoproteins and synthetic polymers. Much of the impetus for liposome design has come from their potential value as drug delivery systems. The development of technologies for the production of such a range of liposome systems has presented interesting problems in the characterisation of their properties. The review addresses the progress that has been made in characterising the surfaces of different types of liposomes with specific reference to their electrophoretic properties and their interpretation and the physical interactions between liposomal bilayers.     

Aqueous dispersions of cholesteric liquid crystals and their optical properties

This paper reports on a theoretical and experimental investigation of light transmission by a layer of aqueous suspension of polymer dispersed cholesteric liquid crystals (CLC) with a helical molecular structure. The transmission spectra and the spectral order parameter of the supramolecular texture of CLC confirm the high degree of ordering of CLC molecules in the spherical cells. Cell morphology and the spectral dependences of light transmission by the plane-parallel layer of CLC aqueous dispersion are considered.     

Methods for obtaining solid dispersions of drugs and their properties

The possibility of improving the solubility of drugs by obtaining solid dispersions (SDs) with polymers is demonstrated. The solubility of these SDs is dependent both on the nature of drug and polymer and on the conditions of their preparation. IR spectroscopy of the obtained SDs and the analysis of results found in literature indicate that inclusion complexes are formed within them.

     

Preparation of highly concentrated nanostructured dispersions of controlled size

This article presents the use of a shearing procedure for the preparation of stable nanostructured dispersions of lipid mesophases. This new application of the shearing technique is compared with the well-established ultrasonication method for the emulsification of these mesophases in water in terms of particle size, particle size distribution and available concentration range. With a laboratory-built shear device based on a Couette cell, it was possible to produce high quantities of internally self-assembled emulsion particles of controlled size at concentrated hydrophobic phase contents (_o) of up to 70 wt%. The concentration limit of 70 wt% could be reached however, the maximum attainable concentration depended on the internal structure type of the particles. The limit was thus easily attained for emulsified microemulsions (EME) as well as for the emulsified inverse hexagonal phase (H₂), whereas it was found to be lower for emulsified discontinuous (Fd3m) and bicontinuous (Pn3m) cubic phases. Moreover, by shearing, it was possible to keep the size of the particles relatively constant when increasing _o, whereas the particle size significantly increased with _o when ultrasonication was employed. By means of ultrasonication, the hydrodynamic radius of the particles could be tuned linearly between 85 to 180 nm as a function of _o up to a maximum of 20 to 30 wt%. Below the maximum concentration limit, particles displayed a well-controlled size.     

Preparation and optical properties of Eu(III) complexes J-aggregate formed on the surface of silver nanoparticles

Ag colloidal nanoparticles coated with Eu(TTA)₃ · 2H₂O complexes were prepared, and it was found that Eu(TTA)₃ · 2H₂O complexes J-aggregate was formed on the surface of Ag nanoparticles according to a red shift (18.2 nm) in UV–Vis spectra. However, there had similar excitation wavelength, which was attributed to existence of Ag nanoparticles. Highly luminescent properties of Ag colloidal nanoparticles were observed, and it was believed to result from low energy transfer between Eu(III) complexes and Ag and the large electromagnetic field arising from the excitation of surface plasmon polariton of Ag nanoparticles.     

Preparation of rapidly disintegrating tablets containing itraconazole solid dispersions

The disintegratability of tablets prepared from two types of solid dispersions containing the water-soluble polymer TC-5 and the enteric polymer HP-55 as an excipient were compared. The disintegratability was better in the tablets of solid dispersions containing non-water-soluble HP-55 than those containing TC-5. In consideration of the dissolubility of solid dispersions containing HP-55, the mean diameter of the solid dispersion (coating powder) must be controlled to 120 microm or less, but as this markedly increases the adhesion/aggregation tendency of the particles (angle of repose: 47 degrees ), control of the adhesion/aggregation tendency emerged as another problem. Therefore, surface-modification was performed in a high-speed agitating granulator using 0.1% light anhydrous silicic acid as a surface modifier, and marked improvement in the flowability was observed. This made continuous tableting using a rotary tablet machine possible even with the poorly flowable solid dispersions. Also, in tableting of the solid dispersions, no recrystallization of amorphous itraconazole by the tableting pressure was observed, and the tablets maintained satisfactory dissolubility. Moreover, it was possible to obtain the rapidly disintegrating tablets with very satisfactory properties, i.e., a tablet hardness of 30 N or higher and a disintegration time of 30 s or less, by the addition of croscarmellose as a disintegrant at 2% to the surface-modified solid dispersion and selection of the tableting pressure at 4.5 kN.