Core/shell nanoparticles for pH-sensitive delivery of doxorubicin.

Core/shell nanoparticles with lipid core were prepared and characterized as pH-sensitive delivery system of anticancer drug. The lipid core is composed of drug-loaded lecithin and the polymeric shell is composed of Pluronics (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) tri-block copolymer, F-127). Based on the preparation method in the previous report by us, the freeze-drying of drug-loaded lecithin was performed in the F-127 aqueous solution containing trehalose used as a cryoprotectant to form stabilized core/shell nanoparticles. For the application of core/shell nanoparticles as a pH-sensitive drug delivery system for anticancer drug, doxorubicin was loaded into the core/shell nanoparticles and the drug loading amount and drug release behavior in response to pH change were observed.

Solvent-responsive polymer nanocapsules with controlled permeability: encapsulation and release of a fluorescent dye by swelling and deswelling.

A solvent-responsive polymer nanocapsule swells and deswells in response to a change in solvent composition, and the permeability of the shell of the nanocapsule can be controlled simply by swelling and deswelling; encapsulation and release of a fluorescent dye is achieved by a swelling-deswelling-swelling cycle.

Vesicle-to-spherical micelle-to-tubular nanostructure transition of monomethoxy-poly(ethylene glycol)-poly(trimethylene carbonate) diblock copolymer.

Recently, we reported a temperature-sensitive biodegradable diblock copolymer of monomethoxy-poly(ethylene glycol)-b-poly(trimethylene carbonate) (mPEG-PTMC; Macromolecules 2007, 40, 5519-5525). In this paper, we report the detailed morphological transition of the polymer in water as a function of polymer concentration and temperature, using cryo-transmission electron microscopy (cryo-TEM). At a low polymer concentration (0.05 wt %), the mPEG-PTMC diblock copolymers formed vesicles in water. On the other hand, vesicle-to-micelle transition was observed as the polymer concentration increased. The polymer predominantly formed micelles above 2.0 wt %. In the 2.0 wt % polymer solution, the mPEG-PTMC underwent spherical micelle-to-tubular nanostructure transition as the temperature increased from 10 to 40 degrees C, and the transition accompanied an increase in turbidity of the polymer aqueous solution due to the increase in the apparent size of the polymer aggregates. Here, we report that the morphology of vesicles, spherical micelles, and tubular nanostructures is reversibly controlled by a thermosensitive polymer of mPEG-PTMC and the variation of the morphology can be carefully traced by using cryo-TEM. This paper will not only provide an important method for morphological control of an amphiphilic polymer but also improve our understanding of a temperature-sensitive transition mechanism of the polymer.

Regulation of CD40 reconstitution into a liposome using different ratios of solubilized LDAO to lipids.

The integral membrane protein CD40 was found on the surface of B lymphocytes that interact with CD40L on T cells during the immune response. The hydrophobic transmembrane domains of membrane proteins can be stabilized in detergent or in lipid bilayers such as liposomes. Membrane proteins can be incorporated into the liposome in a similar fashion to the way they are handled in vivo. In this study, a large amount of full-sequence CD40 was produced using a bacterial system that contained a Mistic construct. The CD40 was then reconstituted into liposomes by detergent-mediated reconstitution. All stages in the process of liposome disruption with various detergent ratios were easily observed by monitoring the optical density. The structure of the liposome and the reconstitution of CD40 were confirmed by cryo-TEM. The results of the present study show that the detergent ratio had an effect on the structure of the liposome and the amount of CD40 that was reconstituted into the liposome.

Loading of gold nanoparticles inside the DPPC bilayers of liposome and their effects on membrane fluidities.

Gold nanoparticles were loaded in the bilayer of dipalmitoylphosphatidylcholine (DPPC) liposomes, named as gold-loaded liposomes. Above the gel to liquid-crystalline phase transition temperature, membrane fluidities of DPPC liposomes were changed by loading the gold nanoparticles. Compared with liposomes without loading the gold nanoparticles, gold-loaded liposomes showed the lower fluorescence anisotropy values. That is, the membrane fluidities of DPPC bilayer were increased by loading the gold nanoparticles. The membrane fluidities were increased as the amount of gold nanoparticles increased. The existence of gold nanoparticles in the DPPC bilayer was observed by transmission electron microscopy. Through the energy dispersive X-ray spectrometer, the particles in DPPC bilayer were confirmed to be gold nanoparticles.

Effects of silver nanoparticles on the fluidity of bilayer in phospholipid liposome.

This paper describes the formation and characterization of liposome entrapping the silver nanoparticles in bilayer. Silver nanoparticles were entrapped in the bilayer of dipalmitoylphosphatidylcholine (DPPC) liposome, named as silver-loaded liposome. Specifically, above the gel to liquid-crystalline phase transition temperature of this lipid (i.e., 41 degrees C), it was observed that membrane fluidities of silver-loaded liposomes were increased, and fluorescence anisotropy values were reduced from 0.114 to 0.097. This might be due to the structural modifications and interactions between DPPC molecules and silver nanoparticles within the bilayer. It was also confirmed that silver nanoparticles were entrapped in hydrophobic region of lipid bilayer with transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) measurements.

Control over micro-fluidity of liposomal membranes by hybridizing metal nanoparticles.

This study introduces a facile method to hybridize metal nanoparticles with lipid vesicles, which allows us to control over their membrane micro-fluidity. We have fabricated these hybrid liposomes by directly hybridizing metal nanoparticles with lipid bilayers solely consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC). For this, we have used the dehydration and rehydration method. Characterizing their morphology and micro-fluidity, in which we have used electron microscopy and fluorescence anisotropy spectroscopy, enables us to demonstrate that metal nanoparticles with different surface properties create interactions with either phosphorus end groups or hydrophobic tails of DPPC, thereby resulting in decrease in micro-fluidity of the assembled lipid membranes, especially for the hydrophobic layers. Our approach to hybridize metal nanoparticles in between lipid layers offers a flexible means that allows us to obtain a liposome system with more controllable membrane properties.

Core/Shell nanoparticles with lecithin lipid cores for protein delivery.

Core/shell nanoparticles with lipid core, were prepared and characterized as a sustained delivery system for protein. The lipid core is composed of protein-loaded lecithin and the polymeric shell is composed of Pluronics (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer, F-127). Based on the preparation method in the previous report by us, the freeze-drying of protein-loaded lecithin was performed in the F-127 aqueous solution containing trehalose used as a cryoprotectant to form stabilized core/shell nanoparticles. Cryo-TEM (transmittance electron microscopy) and a particle size analyzer were used to observe the formation of stabilized core/shell nanoparticles. For the application of core/shell nanoparticles as a protein drug carrier, lysozyme and vascular endothelial growth factor (VEGF) were loaded into the core/shell nanoparticles by electrostatic interaction, and the drug release pattern was observed by manipulating the polymeric shell.

Formation of core/shell nanoparticles with a lipid core and their application as a drug delivery system.

A novel preparation method for core/shell nanoparticles with a drug-loaded lipid core was designed and characterized. The lipid core is composed of lecithin and a drug, and the polymeric shell is composed of Pluronics (poly(ethylene oxide)-poly (propylene oxide)-poly(ethylene oxide) triblock copolymer, F-127). For the formation of stabilized core/shell nanoparticles, freeze-drying was performed in the presence of trehalose used as a cryoprotectant. Cryogenic transmittance electron microscopy (cryo-TEM), differential scanning calorimetry (DSC), and a particle size analyzer were used to observe the formation of the stabilized core/shell nanoparticles. For the application of the core/shell nanoparticles as a drug carrier, paclitaxel, a potent anticancer drug, was loaded into the core/shell nanoparticles, and the drug loading amount and the drug release pattern were observed.