Treatment of bleomycin-induced pulmonary fibrosis by inhaled tacrolimus-loaded chitosan-coated poly(lactic-<i>co</i>-glycolic acid) nanoparticles

Lee, Changkyu,Seo, Jisoo,Hwang, Ha Shin,Thao, Le Quang,Lee, Seunghyun,Lee, Eun Seong,Lee, Eun Hee,Choi, Han-Gon,Youn, Yu Seok Elsevier 2016 BIOMEDICINE AND PHARMACOTHERAPY Vol.78 No.-

<P><B>Abstract</B></P> <P>Pulmonary fibrosis is a chronic lung disease characterized by inflammation and collagen deposition, with an estimated mortality rate exceeding 70%. Here, we evaluated the therapeutic effectiveness of inhaled tacrolimus-loaded chitosan-coated poly(lactic-<I>co</I>-glycolic acid) nanoparticles (chitosan TAC PLGA-NPs) in a bleomycin-induced pulmonary fibrosis mouse model. Chitosan TAC PLGA-NPs were fabricated using an o/w emulsification diffusion method, and uncoated TAC PLGA-NPs and chitosan TAC PLGA-NPs were spherical with approximate diameters of 320 and 441nm, respectively. The zeta potential of chitosan TAC PLGA-NPs (+13.6mV) was increased significantly by chitosan-coating versus uncoated TAC PLGA-NPs (−28.3mV). The incorporation efficiency of tacrolimus was 37.7%, and the tacrolimus was gradually released until about 5day. Direct inhalation of chitosan TAC PLGA-NPs (TAC 180μg/mouse) twice a week produced marked anti-fibrotic efficacy in mice with bleomycin-induced pulmonary fibrosis, which was much better than the efficacy resulting from daily oral administration (TAC 300μg/mouse) on the basis of hematoxylin/eosin and Masson’s trichrome staining assessments. Imaging of lung deposition showed that chitosan TAC PLGA-NPs were located well in the lungs and gradually faded over 96h. The pulmonary delivery of tacrolimus could be therapeutically efficacious for treating pulmonary fibrosis. TAC-loaded PLGA nanoparticles should be considered to be an efficient sustained-release type inhalation system that reduces administration frequency and relevant side effects.</P>

Long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes

Lee, Changkyu,Choi, Ji Su,Kim, Insoo,Oh, Kyung Taek,Lee, Eun Seong,Park, Eun-Seok,Lee, Kang Choon,Youn, Yu Seok Dove Medical Press 2013 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.8 No.-

<P>Inhalable glycol chitosan-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing palmitic acid-modified exendin-4 (Pal-Ex4) (chitosan Pal-Ex4 PLGA NPs) were prepared and characterized. The surface morphology, particle size, and zeta potential of chitosan Pal-Ex4 PLGA NPs were investigated, and the adsorption and cytotoxicity of chitosan Pal-Ex4 PLGA NPs were evaluated in human lung epithelial cells (A549). Finally, the lung deposition characteristics and hypoglycemia caused by chitosan Pal-Ex4 PLGA NPs were evaluated after pulmonary administration in imprinting control region (ICR) and type 2 diabetic db/db mice. Results showed that chitosan Pal-Ex4 PLGA NPs were spherical, compact and had a diameter of ~700 nm and a positive surface charge of +28.5 mV Chitosan-coated PLGA NPs were adsorbed onto A549 cells much more so than non-coated PLGA NPs. Pal-Ex4 release from chitosan-coated PLGA NPs was delayed by as much as 1.5 days as compared with chitosan-coated Ex4 PLGA NPs. In addition, chitosan-coated PLGA NPs remained in the lungs for ~72 hours after pulmonary administration, whereas most non-coated PLGA NPs were lost at 8 hours after administration. Furthermore, the hypoglycemic efficacy of inhaled chitosan Pal-Ex4 PLGA NPs was 3.1-fold greater than that of chitosan Ex4 PLGA NPs in db/db mice. The authors believe chitosan Pal-Ex4 PLGA NPs have considerable potential as a long-acting inhalation delivery system for the treatment of type 2 diabetes.</P>

Self-assembled glycol chitosan nanogels containing palmityl-acylated exendin-4 peptide as a long-acting anti-diabetic inhalation system

Lee, Juho,Lee, Changkyu,Kim, Tae Hyung,Lee, Eun Seong,Shin, Beom Soo,Chi, Sang-Cheol,Park, Eun-Seok,Lee, Kang Choon,Youn, Yu Seok Elsevier 2012 Journal of controlled release Vol.161 No.3

<P>Inhalable deoxycholic acid-modified glycol chitosan (DOCA-GC) nanogels containing palmityl acylated exendin-4 (Ex4-C16) were prepared by self-assembly and characterized physicochemically. The lung deposition of DOCA-GC nanogels was monitored using an infrared imaging system, and the hypoglycemia caused by Ex4-C16-loaded DOCA-GC nanogels was evaluated after pulmonary administration in type 2 diabetic db/db mice. The cytotoxicities and lung histologies induced by DOCA-GC nanogels were examined in human lung epithelial cells (A549 and Calu-3) and db/db mice, respectively. Results showed that the DOCA-GC nanogels prepared were spherical and compact and had a diameter of ~220 nm. Although the incorporation of Ex4-C16 (50.97.8%) into DOCA-GC nanogels was significantly lower than that of Ex4 (81.44.9%), the Ex4-C16 release from DOCA-GC nanogels was greatly delayed vs. Ex4. DOCA-GC nanogels were deposited rapidly after pulmonary administration and remained in the lungs for ~72 h. Furthermore, the hypoglycemic duration of inhaled Ex4-C16 nanogels was much greater than that of Ex4 nanogels in db/db mice. Cytotoxicity results of DOCA-GC nanogels were considered acceptable, and the tissue histologies of mouse lungs administered nanogels did not show any significant difference vs. control lungs. The authors believe that Ex4-C16 DOCA-GC nanogels offer a long-acting inhalation delivery system for treating type 2 diabetes.</P>

관광 데이터의 양적 보완을 위한 이종 빅데이터의 활용

이창규(Changkyu Lee),이상원(Sangwon Lee),전규희(Kyuhui Jun),김수빈(Subin Kim),이재관(Jaegwan Lee),임희수(Heesoo Rhim),최진무(Jinmu Choi) 대한공간정보학회 2023 한국공간정보학회 학술대회 Vol.2023 No.12

현재의 관광 빅데이터는 다양하고 방대하여 관광 연구와 정책에 활용도가 높다. 관광 데이터는 관광 행위 감소에 영향을 받으며 관광위기요인은 이를 야기할 수 있다. 특히 재해와 같이 예측 및 통제 불가능한 요인에 의한 데이터의 대량 부족은 데이터 기반 결과의 신뢰를 저하할 수 있다. 본 연구에서는 관광 데이터의 보완을 위해 이종 데이터를 접목 활용과 상호보완성 확인 방안을 제시하고자 하였다. 이를 위해 신용카드 데이터와 블로그 데이터를 대상으로 시계열적, 공간적, 시공간적 분석 결과를 비교하였다. 분석 결과, 그 추세와 분포가 유사하였으며 데이터 접목 및 통합 가능성을 확인하였다. 또한, 인구통계학적 정보나 텍스트 정보를 상호보완하여 활용할 수 있음을 확인하였다. 본 연구의 결과는 다종 데이터 접목과 분석, 관광 연구 및 정책 수립에 기여할 수 있을 것으로 기대한다.

재난 상황 파악을 위한 소셜미디어 데이터의 시공간 정보화에 관한 연구

이창규(Changkyu Lee),이상원(Sangwon Lee),이영진(Youngjin Lee),황수연(Suyeon Hwang),김수빈(Subin Kim),최진무(Jinmu Choi) 대한지리학회 2022 대한지리학회 학술대회논문집 Vol.2022 No.6

A novel prototype of albumin nanoparticles fabricated by supramolecular cyclodextrin-adamantane association

Lee, Seunghyun,Lee, Changkyu,Kim, Bomi,Thao, Le Quang,Lee, Eun Seong,Kim, Jong Oh,Oh, Kyung Taek,Choi, Han-Gon,Youn, Yu Seok Elsevier 2016 Colloids and Surfaces B Vol.147 No.-

<P><B>Abstract</B></P> <P>Albumin has been viewed as one of the most attractive biomacromolecules for making nanoparticulate systems due to its biocompatibility and chemical functionality. Thus far, albumin nanoparticles (NPs) are prepared by several limited methods, such as, desolvation, emulsification or high-pressure homogenization. In this article, we introduce a new albumin NPs prototype fabricated <I>via</I> a ‘host’ (β-cyclodextrin)-‘guest’ (adamantane) supramolecular association. These NPs (GC-CD/HSA-ADA NPs) consisted of β-cyclodextrin-modified glycol chitosan (GC-CD) and adamantane-conjugated human serum albumin (HSA-ADA) (GC-CD/HSA-ADA NPs) that were facilely prepared by a consequent dropwise mixing and sonication method. Doxorubicin-loaded GC-CD/HSA-ADA NPs exhibited an appropriate particle size (∼260nm), good physicochemical stability (∼48h), significant HCT116 cell cytotoxicity (IC<SUB>50</SUB>: 0.32μg/ml) and cell internalization. Furthermore, GC-CD/HSA-ADA NPs showed excellent tumor targetability probably due to gp60-mediated transcytosis mechanism because it was markedly accumulated in the tumor site of a HCT116 cell-xenograft mouse. Based on these results, these albumin NPs will be promising for a new NP platform that can be applied for cancer therapy or imaging.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We developed a new prototype of self-assembled albumin nanoparticles. </LI> <LI> The nanoparticles consisted of cyclodextrin-glycol chitosan and adamantane-albumin. </LI> <LI> The nanoparticles were formed <I>via</I> supramolecular cyclodextrin-adamantane association. </LI> <LI> The nanoparticles exhibited remarkable targetability in the HCT116 xenograft tumors. </LI> <LI> These new albumin nanoparticles would be potential as a theranostic carrier. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Near infrared light-responsive heat-emitting hemoglobin hydrogels for photothermal cancer therapy

Lee, Changkyu,Lim, Kyungseop,Kim, Sung Soo,Thien, Le Xuan,Lee, Eun Seong,Oh, Kyung Taek,Choi, Han-Gon,Youn, Yu Seok Elsevier 2019 Colloids and Surfaces B Vol.176 No.-

<P><B>Abstract</B></P> <P>Photothermal therapy (PTT) is an effective means of treating tumors because tumor cells are sensitive to heat. Gold and carbon nanoparticles are used as efficient PTT materials. However, development of a non-toxic biodegradable PTT agent remains a challenge. Here, we developed a hemoglobin (Hb) hydrogel that exhibited excellent PTT effects <I>in vitro</I> and <I>in vivo</I>. Unlike conventional PTT agents, which are toxic and do not decompose completely in the body, the Hb hydrogel was manufactured using only two components: (i) Hb, a natural substance derived from the human body, and (ii) PEG, an FDA-approved polymer. The gelation time of the Hb hydrogels could be controlled by changing the Hb concentration. Because Hb is present at a high concentration (150 mg/ml) in the body, the Hb hydrogel decomposed and was eliminated <I>in vivo</I> without toxicity. The Hb hydrogel showed an excellent PTT effect in response to 808 nm near-infrared (NIR) laser irradiation and had excellent anticancer effects against A549 lung cancer cells both <I>in vitro</I> and <I>in vivo</I>. Blood hematology and blood biochemical assay results from an animal model treated with Hb hydrogel were similar to those of the control group. Importantly, toxicity was not observed based on H&E staining of major organs (heart, liver, spleen, kidneys and lung). Tumors of A549 cell-xenografted mice treated with Hb hydrogel and 808 nm NIR laser irradiation were significantly smaller than those of the control group (23.1 mm<SUP>3</SUP> <I>versus</I> 746.5 mm<SUP>3</SUP>, respectively). This is a first report of a biocompatible photothermal hydrogel based on hemoglobin, and our overall results suggest that Hb hydrogels are commercially-promising PTT systems that have excellent anti-cancer effects.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We developed a prototype of <I>in situ</I> injectable hemoglobin hydrogel forming within 60 s. </LI> <LI> This hydrogel emitted sufficient heat in response to the nearinfra red light irradiation. </LI> <LI> This hydrogel exhibited noticeable ablation effect on the HCT116 cell-based tumors. </LI> <LI> This hemoglobin hydrogel would be potential as a photothermal antitumor agent for colon cancers. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Chlorella-gold nanorods hydrogels generating photosynthesis-derived oxygen and mild heat for the treatment of hypoxic breast cancer

Lee, Changkyu,Lim, Kyungseop,Kim, Sung Soo,Thien, Le Xuan,Lee, Eun Seong,Oh, Kyung Taek,Choi, Han-Gon,Youn, Yu Seok Elsevier 2019 Journal of controlled release Vol.294 No.-

<P><B>Abstract</B></P> <P>Hypoxic tumors are rarely cured because their low oxygen environment restricts the cytotoxicity of many chemotherapeutics by blocking the production of intracellular reactive oxygen species. Inspired by the highly efficient production of oxygen as a waste product of chlorella photosynthesis, we developed an <I>in situ</I> rapidly gelling BSA-PEG–based hydrogel depot system that contains chlorella and gold nanorods, namely Chlorella AuNRs BSA-Gel. The entrapped chlorella in our gel efficiently generated a high level of oxygen and oxygenated hemoglobin <I>via</I> photosynthesis in response to 660-nm light <I>in vitro</I> and <I>in vivo</I>, respectively. The incorporated gold nanorods showed excellent performance in precisely increasing the surrounding temperature to 41–42 °C responding to 808-nm near-infrared laser, which presumably played a supporting role in expanding the tumor vasculature and thereby facilitating the delivery of doxorubicin and oxygen to hypoxic tumors of mice. Our results showed that a combined therapy of Chlorella AuNRs BSA-Gel plus Dox followed by irradiation at 660 nm and 808 nm significantly abolished 4 T1 breast cancer cell-xenografted tumors of BALB/C mice. We believe that our oxygen-generating and mild heat-emitting hydrogel should be considered to be a valid prototype of a local depot system for treatment of hypoxic tumors.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

High-resolution conductive patterns fabricated by inkjet printing and spin coating on wettability-controlled surfaces

Lee, Changkyu,Kang, Byung Ju,Oh, Je Hoon Elsevier S.A. 2016 Thin Solid Films Vol.616 No.-

<P><B>Abstract</B></P> <P>In this study, we develop a simple and low-cost surface wettability patterning based on soft lithography processes such as nano-imprint lithography (NIL) and micro-contact printing (μCP) to fabricate high-resolution conductive patterns using two different solution processes: inkjet printing and spin coating. An epoxy-based photoresist layer was imprinted by an elastomeric stamp during the NIL process to produce negative micro-structures in the epoxy-based photoresist layer. To form surface wettability contrast, a hydrophobic fluorocarbon film was transferred onto the top surface of the imprinted epoxy-based photoresist layer using μCP. The epoxy-based photoresist layer was UV-treated before the μCP process in order to increase surface wettability contrast; the hydrophilic imprinted patterns surrounded by hydrophobic surfaces were fabricated in the epoxy-based photoresist layer. After printing Ag ink on the imprinted epoxy-based photoresist layer, high-resolution printed line array and square spiral patterns with line width and gap distance of several micrometers can be fabricated with an aid of high surface wettability contrast. Even though well-defined high-resolution conductive patterns with electrical resistivity lower than 6μΩcm can be obtained regardless of the solution processes, inkjet printing seems more efficient from the viewpoint of the amount of ink used in each solution process. The surface wettability patterning suggested in this study is expected to be used in the fabrication of high-resolution conductive patterns in printed electronics.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Surface wettability patterning was performed using soft lithography process. </LI> <LI> Thickness of fluorocarbon films should be controlled to fabricate well-defined patterns. </LI> <LI> Precise positioning of printed ink is not necessary due to the lift-off process. </LI> <LI> Both inkjet printing and spin coating can produce high-resolution patterns. </LI> <LI> Electrical resistivity of the ~7μm wide pattern is lower than 6μΩcm. </LI> </UL> </P>

Facile fabrication of highly photothermal-effective albumin-assisted gold nanoclusters for treating breast cancer

Lee, Sungin,Lee, Changkyu,Park, Sanghyun,Lim, Kyungseop,Kim, Sung Soo,Kim, Jong Oh,Lee, Eun Seong,Oh, Kyung Taek,Choi, Han-Gon,Youn, Yu Seok Elsevier 2018 International journal of pharmaceutics Vol.553 No.1

<P><B>Abstract</B></P> <P>Gold nanoclusters (AuNCs) have been considered to be a promising candidate for hyperthermia-based anticancer therapy. Herein, we introduce albumin-assisted AuNCs composed of small gold nanoparticles (AuNPs, <6 nm) assembled with strands of polyallylamine (PAH), which exhibited strong surface plasmon resonance upon near-infrared (NIR, ∼808 nm) laser irradiation and good <I>in vivo</I> stability. Our albumin-assisted PAH-AuNCs (BSA/PAH-AuNCs) were facilely fabricated as a top-down process by a simple ultrasonication after the preparation of large nano-aggregates of PAH-AuNPs. Albumin played a critical role as a stabilizer and surfactant in making loosely associated large aggregates and thereby producing small gold nanoclusters (∼60 nm) of slightly negative charge upon ultrasonication. The prepared BSA/PAH-AuNCs displayed excellent hyperthermal effects (∼60 °C) in response to ∼808-nm NIR laser irradiation in a 4T1 cell system <I>in vitro</I> and in 4T1 cell tumor xenograft mice <I>in vivo</I>, indicating their remarkable potential to suppress breast cancer growth, without almost no significant toxicity in histology. Consequently, our gold nanoclusters should be considered as a promising photothermal agent that are easy to manufacture and exhibit marked anticancer effects in terms of tumor ablation.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>