• 한국고분자학회:학술대회논문집
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• 한국고분자학회 2006년도 IUPAC International Symposium on Advanced Polymers for Emerging Technologies
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• pp.54-55
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• 2006

Polymeric micelles, supramolecular assemblies of block copolymers, are useful nanocarriers for the systemic delivery of drugs and genes. Recently, novel polymeric micelles with various functions such as the targetability and stimuli-sensitivity have been emerged as promising carriers that enhance the efficacy of drugs and genes with minimal side effects. This presentation focuses our recent approach to the preparation of functional block copolymers that are useful for constructing smart micellar delivery systems in advanced therapeutics, including chemo-gene therapy. Particular emphasis is placed on the characteristic behaviors of intracellular environment-sensitive micelles that selectively exert drug activity and gene expression in live cells.

• Journal of Pharmaceutical Investigation
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• 제38권3호
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• pp.163-169
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• 2008

Liposomes are spherical vesicles composed of lipid bilayer membranes. However, the conventional liposomes have been found to be plagued by rapid opsonization and taken up by the reticuloendothelial system (RES), resulting in shortened circulation time and limited intracellular uptake to target cell. In this study, polyethyleneglycol-cationic liposomes (PCL) containing cationic lipid and DSPE-mPEG were prepared by thin film cast-hydration method. The PEG liposomes had approximately $97.0{\pm}1.3\;nm$ of mean particle diameter and $-21.7{\pm}1.2\;mV$ of zeta potential value. PCL had $96.4{\pm}1.8\;nm$ of mean particle diameter and $-8.7{\pm}1.1\;mV$ of zeta potential value with a decrease of about 10 mV compared to the PEG liposomes. Loading of model drug, doxorubicin (DOX), in liposomes were carried out by using remote loading method and the loading efficiency of DOX in liposomes was about $95.0{\pm}1.9%$. Intracellular uptake and cytotoxicity of PCL were higher than that of PEG liposomes to murine B16F10 melanoma cells. In addition, anti-tumor activity of PCL was similar to that of PEG liposomes on growth of A549 human lung carcinoma in BALB/c mice. Consequently, PCL modified with cationic lipid may be applicable as anticancer drug carriers that can increase intracellular uptake and therapeutic efficacy.

• Macromolecular Research
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• 제15권6호
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• pp.513-519
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• 2007

Self-assembled nanoparticles have great potential to act as vehicles for hydrophobic drug delivery. Understanding nanoparticle cellular internalization is essential for designing drugs intended for intracellular delivery. Here, the endocytosis and exocytosis of fluorescein isothiocyanate (FITC)-conjugated glycol chitosan (FGC) self-assembled nanoparticles were investigated by flow cytometry and confocal microscopy. The cellular internalization of FGC nanoparticles was initiated by nonspecific interactions between nanoparticles and cell membranes. Although adsorptive endocytosis of the nanoparticles occurred quickly, significant amounts of FGC nanoparticles were exocytosed, particularly in the early stage of endocytosis. The amount of exocytosed nanoparticles was dependent on the pre-incubation time with nanoparticles, suggesting that exocytosis is dependent on the progress of endocytosis. FGC nanoparticles internalized by adsorptive endocytosis were distributed in the cytoplasm, but not in the nucleus. In vitro cell cycle analysis demonstrated that FGC nanoparticles delivered paclitaxel into the cytoplasm and were effective in arresting cancer cell growth.

• 공업화학
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• 제34권2호
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• pp.121-125
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• 2023

카세인(casein)은 포유류의 우유에서 발견되는 단백질로 우유에서는 80% 이상 함유되어 있다. 사람의 모유에는 약 20~45%가 포함되어 있으며 생체 적합성이 높아 의료 및 산업 소재로 사용되고 있다. 카세인은 양친매성 구조로 내부는 소수성이기 때문에 수용액에서 마이셀로 자가 조립이 가능하여 난용성 약물을 봉입할 수 있다. 또한, 단백질 고분자 소재로 생분해성을 갖고 있어 약물의 전달체로서 적합한 특징을 가진다. 본 연구에서는 칼슘 이온 외에 마그네슘, 아연, 철 등 생체 내 존재하는 다양한 금속 이온들을 사용하여 각각 효과적인 카세인 나노입자 형성 조건을 규명하였다. 동적 광산란 측정기와 제타 전위 측정을 통해 150 nm 이하의 균일한 사이즈를 유지하고 음전하를 띠는 나노입자가 형성됨을 확인하였다. 또한, 각각의 카세인 나노입자가 HeLa 세포주에서 80% 이상의 생존율을 나타내 낮은 세포 독성을 확인하였고, 카세인 나노입자 내부에 시험 약물로서 나일 레드를 봉입하여 세포 내부로 효과적으로 유입됨을 공초점 현미경으로 입증하였다. 본 실험들을 통해 제조된 카세인 나노입자의 약물 전달체로서의 가능성을 확인하였다.

• Bulletin of the Korean Chemical Society
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• 제34권1호
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• pp.154-158
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• 2013

Development of dual functional liposome has been studied for cancer theragnostics. Therefore, we focused on ultrasound-sensitive liposomes with doxorubicin (DOX) and gadolinium (Gd) as a theragnostic carrier having a potential for cancer therapy and diagnosis. In this study, Gd(III)-DOTA-modified sonosensitive liposomes (GL) was developed using chemically synthesized Gd(III)-DOTA-DPPE lipid. Sonosensitivity of GL to 1 MHz ultrasound induced 25% of DOX release. The relaxivities ($r_1$) of GL were $7.33-10.34\;mM^{-1}s^{-1}$, which was higher than that of MR-bester$^{(R)}$. Intracellular delivery of DOX from GL by ultrasound irradiation was evaluated according to ultrasound intensity, resulting in increase of uptake of DOX released from ultrasound-triggered GLs compared to GL3 or Doxil$^{(R)}$ without ultrasound. Taken together, this study shows that the paramagnetic and sonosensitive liposomes, GL, is a novel and highly effective delivery system for drug with the potential for broad applications in human disease.

• BMB Reports
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• 제49권11호
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• pp.585-586
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• 2016

Extracellular vesicles (EVs) are natural carriers of biomolecules that play central roles in cell-to-cell communications. Based on this, there have been various attempts to use EVs as therapeutic drug carriers. From chemical reagents to nucleic acids, various macromolecules were successfully loaded into EVs; however, loading of proteins with high molecular weight has been huddled with several problems. Purification of recombinant proteins is expensive and time consuming, and easily results in modification of proteins due to physical or chemical forces. Also, the loading efficiency of conventional methods is too low for most proteins. We have recently proposed a new method, the so-called exosomes for protein loading via optically reversible protein-protein interaction (EXPLORs), to overcome the limitations. Since EXPLORs are produced by actively loading of intracellular proteins into EVs using blue light without protein purification steps, we demonstrated that the EXPLOR technique significantly improves the loading and delivery efficiency of therapeutic proteins. In further in vitro and in vivo experiments, we demonstrate the potential of EXPLOR technology as a novel platform for biopharmaceuticals, by successful delivery of several functional proteins such as Cre recombinase, into the target cells.

• Applied Science and Convergence Technology
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• 제24권6호
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• pp.284-288
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• 2015

Anionic small molecules are hard to penetrate the cell membranes because of their negative charges. Encapsulation of small molecules into liposome particles can provide target specific delivery of them. In our previous study, siRNA could be efficiently encapsulated into liposome particles using an asymmetric preparation method of liposomes. In this study, the same method was applied for encapsulation of small anionic fluorescent chemicals such as calcein and indocyanine green (ICG). More than 90% fluorescent chemicals were encapsulated in the asymmetric liposome particles (ALPs). No intracellular fluorescent signal was observed in the tumor cells treated with the unmodified calcein/ALPs and ICG/ALPs, whereas the surface modification with a cell-penetrating polyarginine peptide (R8 or R12) allows cellular uptake of the ALPs. The results demonstrate that the ALPs encapsulating small anionic drugs will be useful for target-specific delivery after modification of target-specific ligands.

• 한국임상약학회지
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• 제5권2호
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• pp.75-84
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• 1995

Drug delivery by red cells was established to maintain the release of drugs in the blood. The entrapment method by amphotericin B was re-examined and evaluated for obtaining the suitable entrapping conditions without hemolysis. The amphotericin B treatment below $10{\mu}g/ml$ induced the non-hemolysis to entrap daunorubicin into red cells within 10min. Under these conditions intracellular ATP level was decreased as $18\%$. Membrane fluidity and the shape factor of red cells were maintained. To maintain intracellular ATP, ATP and sodium pyruvate were added during the entrapment procedure because hemolysis during the release test would reflect the loss of intracellular ATP that would be postulate the decrease of the viability invivo. Consequently, the addition of ATP in the reaction solution can raise the intracellular level of ATP.

• Journal of Pharmaceutical Investigation
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• 제24권3호
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• pp.131-137
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• 1994

Drug delivery system by the use of red blood cells was established to sustain the release of drugs in the circulatory system by the intravenous injection. The entrapment method by the preswelling technique was re-examined and evaluated for searching the new entrapping conditions without hemolysis. The addition of 4 volume of $0.6{\times}\;hank's$ balanced salt solution (HBSS) into 1 volume of 50% red blood cells suspension did not induce the hemolysis and change the hematocrit level in this experimental condition (within 15 min). Most of daunorubicin could be entrapped into red blood cells within 15 min. While the intracellular adenosine triphosphate (ATP) level followed by the entrapment was reduced to 86% of normal ATP level, the membrane fluidity and the shape factor of red blood cells were not altered. The release rate of daunorubicin from red blood cells was affected by the hemolysis under this condition. To maintain the intracellular ATP in red blood cells, the new reaction buffer was made With the addition of ATP and sodium pyruvate during the entrapment procedure because the hemolysis during the release test would reflect the loss of intracellular ATP that might result in the decrease of the viability in vivo. The addition of ATP raised the intracellular ATP level, which protect the hemolysis during the release test.

• Biotechnology and Bioprocess Engineering:BBE
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• 제6권4호
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• pp.205-212
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• 2001

One of the important characteristics of biological systems os their ability to change im-portant properties in response to small environmental signals. The molecular mechanisms that biological molecules utilize to sense and respond provide interesting models for the development of "smart" polymeric biomaterials with biomimetic properties. An important example of this is the protein coat of viruses, which contains peptide units that facilitate the trafficking of the virus into the cell via endocytosis, then out of the endosome into the cytoplasm, and from there into the nucleus, We have designed a family of synthetic polymers whose compositions have been de-signed to mimic specific peptides on viral coats that facilitate endosomal escape. Our biomimetic polymers are responsive to the lowered pH whinin endosomes, leading to distruption of the en-dosomal membrane and release of important biomolecular druges such as DNA, RNA, peptides and proteins to the cytoplasm before they are trafficked to lysosomes and degraded by lysosomal en-zymes. In this article, we review our work on the design, synthesis and action of such smart, pH-sensitive polymers.