Keun Sang Oh

Glycol chitosan/heparin immobilized iron oxide nanoparticles with a tumor-targeting characteristic for magnetic resonance imaging

We described the preparation of the glycol chitosan/heparin immobilized iron oxide nanoparticles (composite NPs) as a magnetic resonance imaging agent with a tumor-targeting characteristic. The iron oxide nanoseeds used clinically as a magnetic resonance imaging agent were immobilized into the glycol chitosan/heparin network to form the composite NPs. To induce the ionic interaction between the iron oxide nanoseeds and glycol chitosan, gold was deposited on the surface of iron oxide nanoseeds. After the immobilization of gold-deposited iron oxide NPs into the glycol chitosan network, the NPs were stabilized with heparin based on the ionic interaction between cationic glycol chitosan and anionic heparin. FE-SEM (field emission-scanning electron microscopy) and a particle size analyzer were used to observe the formation of the stabilized composite NPs, and a Jobin-Yvon Ultima-C inductively coupled plasma-atomic emission spectrometer (ICP-AES) was used to measure the contents (%) of formed iron oxide nanoseeds as a function of reaction temperature and formed gold deposited on the iron oxide nanoparticles. We also evaluated the time-dependent excretion profile, in vivo biodistribution, circulation time, and tumor-targeting ability of the composite NPs using a noninvasive NIR fluorescence imaging technology. To observe the MRI contrast characteristic, the composite NPs were injected into the tail veins of tumor-bearing mice to demonstrate their selective tumoral distribution. The MR images were collected with conventional T(2)-weighted spin echo acquisition parameters.

Phthalocyanine-Aggregated Polymeric Nanoparticles as Tumor-Homing Near-Infrared Absorbers for Photothermal Therapy of Cancer

Phthalocyanine-aggregated Pluronic nanoparticles were constructed as a novel type of near-infrared (NIR) absorber for photothermal therapy. Tiny nanoparticles (~ 60 nm, FPc NPs) were prepared by aqueous dispersion of phthalocyanine-aggregated self-assembled nanodomains that were phase-separated from the melt mixture with Pluronic. Under NIR laser irradiation, FPc NPs manifested robust heat generation capability, superior to an individual cyanine dye and cyanine-aggregated nanoparticles. Micro- and macroscopic imaging experiments showed that FPc NPs are capable of internalization into live cancer cells as well as tumor accumulation when intravenously administered into living mice. It is shown here that continuous NIR irradiation of the tumor-targeted FPc NPs can cause phototherapeutic effects in vitro and in vivo through excessive local heating, demonstrating potential of phthalocyanine-aggregated nanoparticles as an all-organic NIR nanoabsorber for hyperthermia.

Multi-core vesicle nanoparticles based on vesicle fusion for delivery of chemotherapic drugs.

The Pluronic nanoparticles (NPs) composed of Pluronic (F-68) and liquid polyethylene glycol (PEG, molecular wt: 400) containing docetaxel (DTX) were stabilized with the vesicle fusion. When DTX-loaded Pluronic NPs were mixed with vesicles in the aqueous medium, DTX-loaded Pluronic NPs were incorporated into vesicles to form multi-core vesicle NPs. The morphology and size distribution of multi-core vesicle NPs were observed using FE-SEM, cryo-TEM and a particle size analyzer. To apply multi-core vesicle NPs as a delivery system for DTX, a model anti-cancer drug, the release pattern of DTX was observed and the tumor growth was monitored by injecting the DTX-loaded multi-core vesicle NPs into the tail veins of tumor-bearing mice. We also evaluated the time-dependent excretion profile, inxa0vivo biodistribution, circulation time, and tumor targeting capability of multi-core vesicle NPs using a non-invasive live animal imaging technology.

Enhancement of the Targeting Capabilities of the Paclitaxel-Loaded Pluronic Nanoparticles with a Glycol Chitosan/Heparin Composite

An enhancement of tumor-targeting capability was demonstrated with paclitaxel (PTX)-loaded Pluronic nanoparticles (NPs) with immobilized glycol chitosan and heparin. The PTX-loaded Pluronic NPs were prepared as described in our previous report by means of a temperature-induced phase transition in a mixture of Pluronic F-68 and liquid polyethylene glycol (PEG; molecular weight: 400) containing PTX. The liquid PEG is used as the solubilizer of PTX, and Pluronic F-68 is the polymer that encapsulates the PTX. The glycol chitosan and heparin were immobilized on the surface of the Pluronic NPs in an aqueous medium, and a powdery form of the glycol chitosan/heparin immobilized Pluronic NPs (composite NPs) was obtained by freeze-drying. Field emission scanning electron microscopy and a particle size analyzer were used to observe the morphology and size distribution of the prepared NPs. To apply the composite NPs as a delivery system for the model anticancer drug PTX, the release pattern and pharmacokinetic parameters were observed, and the tumor growth was monitored by injecting the composite NPs into the tail veins of tumor-bearing mice. An enhancement of tumor-targeting capability of NPs was verified by using noninvasive live animal imaging technology to observe the time-dependent excretion profile, the in vivo biodistribution, circulation time, and the tumor-targeting capability of composite NPs.

Pluronic-Based Core/Shell Nanoparticles for Drug Delivery and Diagnosis

Pluronic-based core/shell nanoparticles (NPs) were formed using various strategies such as self-assembly and temperature induced-phase transition. To improve their functionality as a nanomedicine for diagnosis and therapy, the vesicle fusion and layer by layer approach were employed. Because of the hydrophilic nature of the Pluronic shell and the relatively small size, Pluronic-based core/shell NPs were used in order to improve their pharmacokinetic behaviors in drugs and in imaging agents. This review will introduce various types of Pluronic-based core/shell NPs according to their preparation method and formation mechanism. The focus will be on the Pluronic-based core/shell NPs for tumor targeting, stimulated release of proteins, and cancer imaging capabilities.

Docetaxel-loaded composite nanoparticles formed by a temperature-induced phase transition for cancer therapy

Docetaxel-loaded composite nanoparticles were prepared by temperature-induced phase transition of a mixture composed of Pluronic F-68 and liquid Tween 80/soybean oil containing docetaxel. Liquid soybean oil/Tween 80 was used as a solubilizer for docetaxel and Pluronic F-68 to stabilize the liquid soybean oil/Tween 80 containing docetaxel. The phase transition was performed at low temperature to avoid degradation. The docetaxel composite nanoparticles were injected into the tail veins of tumor-bearing mice to evaluate the composite delivery system for the release pattern and the tumor growth. The tumor-targeting capability of composite nanoparticles was verified by noninvasive live animal imaging for the time-dependent excretion profile, the in vivo biodistribution, and the circulation time.

Blood-pool multifunctional nanoparticles formed by temperature-induced phase transition for cancer-targeting therapy and molecular imaging.

Multifunctional nanoparticles (NPs) were prepared based on temperature-induced phase transition in a molten mixture of Lipiodol(®), Tween 80, paclitaxel (PTX), and Pluronic F-68, wherein the Lipiodol(®)/Tween 80 mixture is used as a solubilizer for PTX, and Pluronic F-68 is used for the stabilization of the molten mixture. The morphology and size distribution of optimized multifunctional NPs were observed using transmittance electron microscopy (TEM) and a particle size analyzer. In the optical imaging of tumor-bearing mice using a near-infrared fluorescence (NIRF) imaging system, the multifunctional NPs were evaluated in terms of a time-dependent excretion profile, in vivo biodistribution and tumor-targeting capability compared to free fluorescence dye. In addition, the prolonged circulation of multifunctional NPs was confirmed by enhancement of the blood-pool in live animals using a micro-CT imaging system, because iodine-containing Lipiodol(®) has an X-ray enhancement property. Finally, the anti-tumor efficacy of multifunctional NPs was monitored by injecting the multifunctional NPs into the tail veins of tumor-bearing mice. The multifunctional NPs showed excellent tumor targetability and anti-tumor efficacy in tumor-bearing mice, caused by the enhanced permeation and retention (EPR) effect.

Paclitaxel-loaded poly(lactide-co-glycolide)/poly(ethylene vinyl acetate) composite for stent coating by ultrasonic atomizing spray

Abstract The mixture of poly(lactide-co-glycolide) (PLGA) and poly(ethylene vinyl acetate) (PEVA) forms a homogeneous liquid in an organic solvent such as tetrahydrofuran, and a phase-separated PLGA/PEVA composite can be prepared from it by evaporating the organic solvent. Exploiting this phenomenon, we designed a novel method of preparing a drug-loaded PLGA/PEVA composite and used it for coating drug-eluting stents (DESs). Paclitaxel (PTX), an anticancer drug, was chosen as a model drug. PLGA acts as a microdepot for PTX, and PEVA provides mechanical strength to the coating material. The presence of PLGA in the PLGA/PEVA composite suppressed PTX crystallization in the coating material, and PTX showed a sustained release rate over more than 30 days. The mechanical strength of the PLGA/PEVA composite was better than that of PEVA used as a control. After coating the stent with a PLGA/PEVA composite using ultrasonic atomizing spray, the morphology of the coated material was observed by scanning electron microscopy, and the release pattern of PTX was measured by high-performance liquid chromatography.

Polysaccharide-based Nanoparticles for Gene Delivery

Nanoparticles based on nanotechnology and biotechnology have emerged as efficient carriers for various biopharmaceutical agents including proteins and genes. In particular, polysaccharides have attracted interest of many researchers in the drug delivery field due to their advantages such as biocompatibility, biodegradability, low toxicity, and ease of modification. A number of polysaccharides including chitosan, hyaluronic acid, and dextran, and their derivatives have been widely used as polymeric backbones for the formation of nanoparticles, which can be provided as valuable gene delivery carriers. In this review, we introduce the chemical and physical natures of different polysaccharides particularly used in biomedical applications, and then discuss recent progress in the development of polysaccharide-based nanoparticles for gene delivery.

Multi-core vesicle nanoparticles for controlled delivery of protein drug

AbstractThe Pluronic/poly(ethylene glycol) composite nanoparticles (NPs) composed of Pluronic F-68, liquid poly(ethylene glycol) (PEG; molecular weight, 400) and human growth hormone (hGH) were stabilized with the vesicle fusion. When hGH-loaded Pluronic/PEG composite NPs were mixed with vesicles in the aqueous medium, hGH-loaded Pluronic/PEG composite NPs were incorporated into vesicles to form multi-core vesicle NPs. The morphology and size distribution of multi-core vesicle NPs were observed using field emission scanning electron microscopy, cryo-transmission electron microscopy, and a particle size analyzer. When multi-core vesicle NPs were applied as a delivery system for the protein drug, a sustained release pattern of hGH was observed.n