Changyong Choi

Encapsulation of paclitaxel into lauric acid-O-carboxymethyl chitosan-transferrin micelles for hydrophobic drug delivery and site-specific targeted delivery

Transferrin/PEG/O-carboxymethyl chitosan/fatty acid/paclitaxel (TPOCFP) micelles were tested for suitability as a drug carrier characterized by low cytotoxicity, sustained release, high cellular uptake, and site-specific targeted delivery of hydrophobic drugs. Characterization, drug content, encapsulation efficiency, and in vitro drug release were investigated. When the feeding amount of paclitaxel (PTX) was increased, the drug content increased, but loading efficiency decreased. TPOCFP micelles had a spherical shape, with a particle size of approximately 140-649 nm. In vitro cell cytotoxicity and hemolysis assays were conducted to confirm the safety of the micelles. Anticancer activity and confocal laser scanning microscopy (CLSM) were used to confirm the targeting efficiency of target ligand-modified TPOCFP micelles. Anticancer activity and CLSM results clearly demonstrated that transferrin-modified TPOCFP micelles were quickly taken up by the cell. The endocytic pathway of TPOCFP micelles was analyzed by flow cytometry, revealing transfection via receptor-mediated endocytosis. These results suggest that PTX-encapsulated TPOCFP micelles may be used as an effective cancer-targeting drug delivery system for chemotherapy.

Evaluation of polyethylene glycol-conjugated novel polymeric anti-tumor drug for cancer therapy

A novel polymeric prodrug (PXPEG) was prepared to enhance the solubility of an anti-cancer drug, paclitaxel, in aqueous solutions and decrease the cytotoxicity by PEGylation, which means PEG attached to another molecule. In addition, the targeting ligand, transferrin (TF), was modified to PXPEG to enhance the therapeutic efficacy. The targeting ligand-modified PXPEG (TFPXPEG) was examined by (1)H-NMR to confirm the successful synthesis. The synthesized TFPXPEG had better solubility than the free drug against aqueous solution. The particle size of TFPXPEG was approximately 197.2nm and it had a spherical shape. The MTT assay showed that the anti-tumor efficiency of TFPXPEG was better than that of TF-unmodified PXPEG. In the KB tumor-bearing mouse model, the tumor volume of TFPXPEG treated groups was decreased dramatically by more than 2 fold or 3 fold compared to the PBS or PXPEG treated groups. The in vitro and in vivo evaluation showed that TFPXPEG had better efficacy than that of PXPEG due to the targeting effect of targeting ligands, such as TF.

Protective effects of polysaccharides from Psidium guajava leaves against oxidative stresses.

The aim of this study was to analyze antioxidant properties of a polysaccharide isolated from Psidium guajava leaves (PS-PGL) in vitro including its radical scavenging activities and protective effects against damage to cells as well as in vivo in zebrafish. The water extract of P. guajava leaves (WE-PGL) and PS-PGL showed strong radical scavenging effects in terms of 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, and alkyl radical. Compared to WE-PGL, PS-PGL enhanced all scavenging activities and in particular strongly scavenged the hydroxyl radical (50% inhibitory concentration [IC50], 0.02mg/mL). In addition, PS-PGL exerted a protective effect against hydrogen peroxide-induced oxidative stress and against toxicity to Vero cells. Furthermore, in vivo experiments using zebrafish embryos indicated that treatment with hydrogen peroxide decreased the survival rate and heart-beating rate of zebrafish embryos, whereas these problems were reduced by PS-PGL treatment. Moreover, PS-PGL inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production, lipid peroxidation, and cell death. Taken together, these results suggest that PS-PGL may be useful as a beneficial antioxidant material in the food and cosmetic industries.

Anticancer effect of gene/peptide co-delivery system using transferrin-grafted LMWSC.

A series of ternary complex was designed to deliver psiRNA-bcl2 and (KLA)4 peptide into cancer cells for cancer therapy. The delivered psiRNA-bcl2 induced gene-silencing in a nucleus of cancer cells, while (KLA)4 peptide inhibited cancer growth via mitochondrial apoptosis, indicating that the ternary complexes exerted very strong synergistic effects on cancer growth suppression by acting on psiRNA-bcl2 and (KLA)4 peptide simultaneously. The ternary complexes having a targeting-ligand, transferrin (TfP), were found to be especially effective at binding to the TfP receptor rich cancer cells, HCT119. The plasmid DNA (pDNA) in ternary complexes was completely condensed at various content of LMWSC-PEG-TfP (32-64 times more than pDNA) and released into cells. pDNA in the complexes was protected from DNase present on the exterior of cells. The size (165-248 nm) of ternary complexes with LMWSC-PEG-TfP was increased, but surface charges (3-4.5 mV) were decreased. These results likely occurred because the free amine-group of LMWSC decreased in response to conjugated transferrin. Moreover, transfected ternary complexes with LMWSC-PEG-TfP were not expressed in the normal cells (HEK293), but were over expressed in HCT119 cells. These findings indicate that the ternary complexes can be specifically targeted to HCT119 cancer cells. The useful complexes for gene and peptide delivery had high anticancer activities via a synergistic effect due to co-operative action of psiRNA and (KLA)4 peptide in HCT119 cells.

Stent linker effect in a porcine coronary restenosis model.

In this study, we aimed to evaluate the mechanical effects of different stent linker designs on in-stent restenosis in porcine coronary arteries. We fabricated stents with an open-cell structure composed of nine main cells and three linker structures in model 1 (I-type), model 2 (S-types) and model 3 (U-types)) as well as Model 4, which is similar to a commercial bare metal stent design. The stent cells were 70 mm thick and wide, with a common symmetrical wave pattern. As the radial force increased, the number of main cells increased and the length of linker decreased. Radial force was higher in model 1, with a linear I-linker, than in models with S- or U-linkers. The flexibility measured by three-point bending showed a force of 1.09 N in model 1, 0.35 N in model 2, 0.19 N in model 3, and 0.31 N in model 4. The recoil results were similar in all models except model 4 and were related to the shape of the main cells. The foreshortening results were related to linker shape, with the lowest foreshortening observed in model 3 (U-linker). Restenosis areas in the porcine restenosis model 4 weeks after implantation were 35.4 ± 8.39% (model 1), 30.4 ± 7.56% (model 2), 40.6 ± 9.87% (model 3) and 45.1 ± 12.33% (model 4). In-stent restenosis rates measured by intravascular ultrasound (IVUS) and micro-computed tomography (micro-CT) showed similar trends as percent area stenosis measured by micro-CT. Model 2, with optimized flexibility and radial force due to its S-linker, showed significantly reduced restenosis in the animal model compared to stents with different linker designs. These results suggest that the optimal stent structure has a minimum radial force for vascular support and maximum flexibility for vascular conformability. The importance of the effects of these differences in stent design and their potential relationship with restenosis remains to be determined.

Effects of Silane Concentration on the Silica-Silica Interaction Parameter (αF) of the Silica / Natural Rubber Compound

ABSTRACT ：The silica-silica interaction parameter (α F ) of the silane treated silica filled natural rubber (NR) compoundwas investigated. As silane (TESPT) concentration increased from 2 to 12% (2, 4, 6, 8, 10, 12%), the α F value increasedat the same silica concentration (10, 20, 30, and 40 phr). It seemed the sulfur atoms in TESPT acted as a crosslinking agent in the compound. As silica concentration increased from 10 to 40 phr, the α F value increased at the same silaneconcentration due to increased silica-silica interaction. Keywords ：α F (measure of the in-rubber structure of the filler), silica / silane, silica structure, Wolffs theory, naturalrubber(NR). † 대표저자 E-mail: kkim@dongahtire.co.kr Ⅰ. 서 론 충전제 입자간 상호관계를 관찰하기 위해서는 충전제 입자간 상호작용 계수 (α F ), 1,2 Payne effect 3,4 를 측정하는 방법 등 여러 가지가 있다. Wolff는 충전제 로딩량과 토크 상승값 (T max-min )의 함수관계에서 나타나는 기울기를 α F 로 정의하였고 입자가 충전된 복합소재와 비충전된 복합소재의 토크 상승값을 이용하여 측정하였으며 카본블랙과 실리카의 α F 를 비교하였다. 1,2 한편 Payne은 입자간 관계를 strain sweep으로 표현하였는데 입자간 상호작용은 입자들의 percolation point 이상에서 관찰된다. Wolff의 방법은 컴파운드의 토크 변화를 관찰하여 측정하는 것이기 때문에 입자간 상호작용 뿐만 아니라 컴파운드 내의 3차원적 사슬구조 (3-dimensional network)의 증가를 관찰할 수 있는 이점이 있다.

Blood-compatible and biodegradable polymer-coated drug-eluting stent

A drug-eluting stent (DES) is a metal stent that has been coated with a drug known to suppress restenosis. To prepare a novel DES, a bare metal stent (BMS) was coated with sirolimus (SRL) in a blood-compatible, biodegradable polymer, poly lactic-glycolic acid, grafted with poly ethylene glycol (PLGA-PEG), by an ultrasonic spray method. The PLGA-PEG-coated DES was designed to control the drug release-rate by varying the PEG content in the polymer. The release behavior of SRL from the DES showed a burst-release pattern in 7 days and then sustained-release over 21 days. The amount of SRL released increased with increasing PEG content in the polymer up to 15%. The PLGA-PEG copolymer coated on the stent showed the potential to act as a bio-degradable drug reservoir. In an in vitro platelet adhesion test, the PLGA-PEG15-coated DES showed significantly reduced platelet deposition versus the BMS. The DES revealed anti-thrombotic activity and blood-compatibility presumably due to the increased hydrophilicity of the surface of the stent and the amount of SRL loading corresponding to the high PEG content in the polymer. In an animal study, the restenosis rate was reduced in the PLGA-PEG15-coated DES group (20.2±11.02%) versus the BMS group (44.2±12.11%). The PLGA-PEG15-coated DES inhibited smooth muscle cell (SMC) proliferation and prevented in-stent restenosis (ISR) in in vivo test. We successfully obtained the PLGA-PEG15-coated DES with smooth surface and sustained drug-release properties.

Preparation and Characterization of Lactic Acid Bacteria Encapsuled with Alginate Microsphere

This study is performed to assess the preparation and characterization of lactic acid bacteria (Sterpoccoccus thermophilus) loaded with alginate microsphere using alginate and chitosan for the efficient delivery of lactic acid bacteria to large intestine. Size and morphology of alginate microsphere were confirmed with spherical shape by scanning electronic microscope (SEM). Biodegradation study of alginate was investigated at different buffer solutions (pH 1.2 and 7.4). This result showed that alginate microsphere did not degrade at pH 1.2 buffer solution but it`s degradation occurred from first day at pH 7.4 buffer solution. Survivability test of lactic acid bacteria in alginate microsphere showed that it was keeping activity of lactic acid bacteria by chroma meter. Therefore, the introduction of alginate microsphere might be a potential system to efficiently delivery lactic acid to large intestine.

Simple nanophotosensitizer fabrication using water-soluble chitosan for photodynamic therapy in gastrointestinal cancer cells

The polysaccharide chitosan has abundant cationic amine groups, and can form ion-complexes with anionic molecules such as the strong photosensitizer chlorin e6 (Ce6). In this study, water-soluble chitosan (WSC) was used to fabricate Ce6-incorporated nanophotosensitizers (Abbreviated as ChitoCe6 nanophotosensitizer) via a self-assembling process. This was accomplished by dissolving WSC in pure water and then directly mixing the solution with solid Ce6 causing ion complex formation between WSC and Ce6. The resulting nanophotosensitizer was spherical in shape and had a particle size of less than 300nm. The photodynamic effect of ChitoCe6 nanophotosensitizer was evaluated using gastrointestinal (GI) cancer cells. At in vitro study using SNU478 cholangiocarcinoma cells, ChitoCe6 nanophotosensitizer showed improved Ce6 uptake by tumor cells, reactive oxygen species production, and cellular phototoxicity. An in vivo study using SNU478-bearing nude mice showed that the ChitoCe6 nanophotosensitizer efficiently accumulated in the tumor tissue and inhibited tumor growth more than treatment with Ce6 alone. Furthermore, ChitoCe6 nanophotosensitizer was also efficiently absorbed through tissue layers in an ex vivo study using porcine bile duct explants. ChitoCe6 nanophotosensitizer showed enhanced photosensitivity and photodynamic effects against cancer cells in vitro and in vivo. We present ChitoCe6 nanophotosensitizer as a promising candidate for photodynamic therapy of GI cancer.

Measurements of the Silica-Silica Interaction Parameter (αF) of the Silane treated Silica Filled Natural Rubber Compound

ABSTRACT ：The silica-silica interaction parameter (α F ) of the silane treated silica filled natural rubber (NR) compoundwas investigated. The measured α F values using mass fraction method following Wolffs theory were compared with volumefraction method. As silica concentration increased, the α F value increased for both methods. The value of α F expressedas volume fraction was higher than that of mass fraction, which resulted in large gaps between α F values. The effect ofaccelerator (MBT) concentration on α F values was compared. Keywords ：α F (measure of the in-rubber structure of the filler), silica / silane, silica structure, Wolffs theory, naturalrubber(NR). † 대표저자 E-mail: kkim@dongahtire.co.kr Ⅰ. 서 론 표면이 hydroxyl 그룹으로 이루어져 있는 실리카는 실란과 함께 고무복합소재에 첨가되었을 시 고무사슬과의 3차원적 사슬구조를 형성한다. 따라서, 카본블랙을 첨가했을 시 보다 회전저항력(rolling resistance) 및 노면접지력(traction) 등에서 우수한 물성들을 보인다. 따라서 실리카는 연비 향상과 눈이나 비가 왔을 시 노면접착력이 우수한 성능이 요구되는 타이어의 tread compound 제조에 사용되고 있다. 1 그 동안 실리카의 보강효과, 2 실리카-실란의 반응,