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Park, Kyeongsoon,Kim, Jong-Ho,Nam, Yun Sik,Lee, Seulki,Nam, Hae Yun,Kim, Kwangmeyung,Park, Jae Hyung,Kim, In-San,Choi, Kuiwon,Kim, Sang Yoon,Kwon, Ick Chan Elsevier 2007 Journal of controlled release Vol.122 No.3
<P><B>Abstract</B></P><P>To improve the <I>in vivo</I> tumor targeting characteristics of polymeric nanoparticles, three glycol chitosan (GC-20?kDa, GC-100?kDa, and GC-250?kDa) derivatives with different molecular weights were modified with cholanic acid at the same molar ratio. The resulting amphiphilic glycol chitosan–cholanic acid conjugates self-assembled to form glycol chitosan nanoparticles (GC-20?kDa-NP, GC-100?kDa-NP, and GC-250?kDa-NP) under aqueous conditions. The physicochemical properties of all three glycol chitosan nanoparticles, including degree of substitution with cholanic acid, surface charge, particle size and <I>in vitro</I> stability, were similar regardless of molecular weight. <I>In vivo</I> tissue distribution, time-dependent excretion, and tumor accumulation of glycol chitosan nanoparticles labeled with the near-infrared (NIR) fluorophore, Cy5.5, were monitored in SCC7 tumor-bearing mice, using NIR fluorescence imaging systems. Glycol chitosan nanoparticles displayed prolonged blood circulation time, decreased time-dependent excretion from the body, and elevated tumor accumulation with increasing polymer molecular weight. The results collectively suggest that high molecular weight glycol chitosan nanoparticles remain for longer periods in the blood circulation, leading to increased accumulation at the tumor site. Accordingly, we propose that enhanced tumor targeting by high molecular weight glycol chitosan nanoparticles is related to better <I>in vivo</I> stability, based on a pharmacokinetic improvement in blood circulation time.</P>
Kim, Sung Eun,Yun, Young-Pil,Shim, Kyu-Sik,Jeon, Daniel I.,Park, Kyeongsoon,Kim, Hak-Jun Elsevier 2018 Journal of industrial and engineering chemistry Vol.58 No.-
<P><B>Abstract</B></P> <P>Achilles tendinopathy is a debilitating musculoskeletal condition that causes significant pain and leads to tendon rupture. Cur/PMSs exerted anti-inflammatory effects on LPS-treated tenocytes in a dose-dependent manner by showing significant decreases in the expression of pro-inflammatory markers such as MMP-3 and MMP-13, COX-2, ADAMTS-5, IL-6, and TNF-α. We demonstrated that local injection of Cur/PMSs markedly suppressed the expression of pro-inflammatory markers in tendon tissue of rats with collagenase-induced Achilles tendinopathy. Cur/PMSs remarkably increased the tensile strength of tendon tissue in a dose-dependent manner. Our findings indicate that Cur/PMSs have great potential for tendon tissue healing and restoration in Achilles tendinopathy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The fabricated Cur/PMSs showed sustained release for 28 days. </LI> <LI> Cur/PMSs decreased the expression of pro-inflammatory cytokines in LPS-treated tenocytes. </LI> <LI> Local treatment of Cur/PMSs suppressed the progression of Achilles tendinopathy. </LI> <LI> Cur/PMSs markedly increased the tensile strength of tendon tissue. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Kim, Mu-Hyon,Park, Kyeongsoon,Choi, Kyung-Hee,Kim, Soo-Hong,Kim, Se Eun,Jeong, Chang-Mo,Huh, Jung-Bo MDPI 2015 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.16 No.5
<P>The authors describe a new type of titanium (Ti) implant as a Modi-anodized (ANO) Ti implant, the surface of which was treated by sandblasting, acid etching (SLA), and anodized techniques. The aim of the present study was to evaluate the adhesion of MG-63 cells to Modi-ANO surface treated Ti <I>in vitro</I> and to investigate its osseointegration characteristics <I>in vivo</I>. Four different types of Ti implants were examined, that is, machined Ti (control), SLA, anodized, and Modi-ANO Ti. In the cell adhesion study, Modi-ANO Ti showed higher initial MG-63 cell adhesion and induced greater filopodia growth than other groups. <I>In vivo</I> study in a beagle model revealed the bone-to-implant contact (BIC) of Modi-ANO Ti (74.20% ± 10.89%) was much greater than those of machined (33.58% ± 8.63%), SLA (58.47% ± 12.89), or ANO Ti (59.62% ± 18.30%). In conclusion, this study demonstrates that Modi-ANO Ti implants produced by sandblasting, acid etching, and anodizing improve cell adhesion and bone ongrowth as compared with machined, SLA, or ANO Ti implants. These findings suggest that the application of Modi-ANO surface treatment could improve the osseointegration of dental implant.</P>
Alendronate-Eluting Biphasic Calcium Phosphate (BCP) Scaffolds Stimulate Osteogenic Differentiation
Kim, Sung Eun,Yun, Young-Pil,Lee, Deok-Won,Kang, Eun Young,Jeong, Won Jae,Lee, Boram,Jeong, Myeong Seon,Kim, Hak Jun,Park, Kyeongsoon,Song, Hae-Ryong Hindawi Publishing Corporation 2015 BioMed research international Vol.2015 No.-
<P>Biphasic calcium phosphate (BCP) scaffolds have been widely used in orthopedic and dental fields as osteoconductive bone substitutes. However, BCP scaffolds are not satisfactory for the stimulation of osteogenic differentiation and maturation. To enhance osteogenic differentiation, we prepared alendronate- (ALN-) eluting BCP scaffolds. The coating of ALN on BCP scaffolds was confirmed by scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). An <I>in vitro</I> release study showed that release of ALN from ALN-eluting BCP scaffolds was sustained for up to 28 days. <I>In vitro</I> results revealed that MG-63 cells grown on ALN-eluting BCP scaffolds exhibited increased ALP activity and calcium deposition and upregulated gene expression of Runx2, ALP, OCN, and OPN compared with the BCP scaffold alone. Therefore, this study suggests that ALN-eluting BCP scaffolds have the potential to effectively stimulate osteogenic differentiation.</P>
Kim, Sung Eun,Lee, Jae Yong,Shim, Kyu-Sik,Lee, Sunghee,Min, Kyoengwoo,Bae, Ji-Hoon,Kim, Hak-Jun,Park, Kyeongsoon,Song, Hae-Ryong Elsevier 2018 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Vol.114 No.-
<P><B>Abstract</B></P> <P>The aim of this study was to investigate the effects of a sulfasalazine-containing hyaluronic acid (SASP/HA) systems on <I>in vitro</I> anti-inflammation and the alleviation of cartilage degradation in both lipopolysaccharide (LPS)-stimulated synoviocytes and a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). The SASP/HA resulted in long-term release of SASP from the SASP/HA for up to 60 days in a sustained manner. <I>In vitro</I> studies performed using real-time polymerase chain reaction (PCR) assay revealed that the SASP/HA was able to effectively and dose-dependently inhibit the mRNA expression levels of pro-inflammatory cytokines such as matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in LPS-stimulated synoviocytes. <I>In vivo</I> studies showed that intra articular injection of SASP/HA greatly reduced the MIA-stimulated mRNA expression of MMP-3, COX-2, IL-6, and TNF-α in blood. Furthermore, these significant anti-inflammatory effects of SASP/HA contributed markedly to the alleviation of progression of MIA-induced OA and cartilage degradation, as demonstrated by X-ray, micro-computed tomography (micro-CT), gross findings, and histological evaluations. Therefore, our findings indicated that the long-term and sustained delivery of SASP using HA can play a therapeutic role in alleviating inflammation as well as protecting against cartilage damage in OA.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Sulfasalazine-hyaluronic acid for long-term delivery was prepared. </LI> <LI> SASP-HA suppressed the levels of pro-inflammatory cytokines in LPS-treated synoviocytes. </LI> <LI> SASP-HA effectively inhibited inflammation and cartilage destruction in OA rat model. </LI> <LI> SASP-HA prevented the progression of OA in rat models. </LI> </UL> </P>
Kim, Sung Eun,Yun, Young-Pil,Shim, Kyu-Sik,Kim, Hak-Jun,Park, Kyeongsoon,Song, Hae-Ryong Institute of Physics Publishing Ltd 2016 Biomedical Materials Vol.11 No.5
<P>The aim of this study was to evaluate the in vitro osteogenic effects and in vivo new bone formation of three-dimensional (3D) printed alendronate (Aln)-releasing poly(caprolactone) (PCL) (Aln/PCL) scaffolds in rat tibial defect models. 3D printed Aln/PCL scaffolds were fabricated via layer-by-layer deposition. The fabricated Aln/PCL scaffolds had high porosity and an interconnected pore structure and showed sustained Aln release. In vitro studies showed that MG-63 cells seeded on the Aln/PCL scaffolds displayed increased alkaline phosphatase (ALP) activity and calcium content in a dose-dependent manner when compared with cell cultures in PCL scaffolds. In addition, in vivo animal studies and histologic evaluation showed that Aln/PCL scaffolds implanted in a rat tibial defect model markedly increased new bone formation and mineralized bone tissues in a dose-dependent manner compared to PCL-only scaffolds. Our results show that 3D printed Aln/PCL scaffolds are promising templates for bone tissue engineering applications.</P>
Heparin–deoxycholic acid chemical conjugate as an anticancer drug carrier and its antitumor activity
Park, Kyeongsoon,Lee, Gee Young,Kim, Yoo-Shin,Yu, Mikyung,Park, Rang-Woon,Kim, In-San,Kim, Sang Yoon,Byun, Youngro Elsevier 2006 Journal of controlled release Vol.114 No.3
<P><B>Abstract</B></P><P>A chemically modified heparin–DOCA (HD) conjugate was developed as a drug carrier for cancer therapy. HD conjugate was found to have markedly low anticoagulant activity and to form self-assembled nanoparticles in aqueous condition. We observed that HD conjugate prevented squamous cell carcinoma (SCC) and human umbilical vascular endothelial cell (HUVEC) proliferation during BrdU incorporation assays. Here, we prepared doxorubicin-loaded heparin nanoparticles by entrapping doxorubicin into the amphiphilic HD conjugate by physical interaction and characterized the properties of these nanoparticles using Dynamic Light Scattering (DLS) and Atomic Force Microscope (AFM). In this study, doxorubicin-loaded heparin nanoparticles were designed to improve the antitumor effects of nano-sized particles (range of 180 to 210?nm) at high drug-loading efficiencies in the range 64% to 96%. These doxorubicin-loaded heparin nanoparticles displayed sustained drug release patterns. It was confirmed in vivo toxicity studies that HD conjugate did not induce unexpected side effects and that DHN 20 was safer than free DOX. An in vivo study showed that HD conjugate, doxorubicin and DHN 20 (one of doxorubicin-loaded heparin nanoparticles) induced tumor volume reductions of 43%, 56% and 74%, respectively, relative to the saline treated control. These results suggest that the drug-entrapped with heparin nanoparticles might provide a novel therapy for SCC.</P>