• BMB Reports
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• v.43 no.8
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• pp.561-566
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• 2010

Though protein transduction domains (PTDs) are well known for the delivery of exogenous therapeutic proteins into living cells, the overall low efficiency of transduction is a serious obstacle. We investigated the effect of bog blueberry anthocyanins (BBA) on protein transduction efficiency and found that BBA enhanced the transduction efficiencies of Tat-SOD fusion protein into HeLa cells and mice skin. The enzymatic activities in the cells and skin tissue in the presence of BBA were markedly increased compared to controls. Further, BBA did not demonstrate any cell toxicity at various concentrations. Although the mechanism is not fully understood, we suggest that BBA might alter the conformation of the membrane, which would indicate that BBA can be used as a protein transduction enhancer for the efficient delivery of therapeutic proteins for a variety of disorders.

• Biotechnology and Bioprocess Engineering:BBE
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• v.6 no.4
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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.

• Nuclear Engineering and Technology
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• v.38 no.5
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• pp.399-404
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• 2006

Noninvasive molecular targeting in living subjects is highly demanded for better understanding of such diverse topics as the efficient delivery of drugs, genes, or radionuclides for the diagnosis or treatment of diseases. Progress in molecular biology, genetic engineering and polymer chemistry provides various tools to target molecules and cells in vivo. We used chitosan as a polymer, and $^{99m}Tc$ as a radionuclide. We developed $^{99m}Tc-galactosylated$ chitosan to target asialoglycoprotein receptors for nuclear imaging. We also developed $^{99m}Tc-HYNIC-chitosan-transferrin$ to target inflammatory cells, which was more effective than $^{67}Ga-citrate$ for imaging inflammatory lesions. For an effective delivery of molecules, a longer circulation time is needed. We found that around 10% PEGylation was most effective to prolong the circulation time of liposomes for nuclear imaging of $^{99m}Tc-HMPAO-labeled$ liposomes in rats. Using various characteristics of molecules, we can deliver drugs into targets more effectively. We found that $^{99m}Tc-labeled$ biodegradable pullulan-derivatives are retained in tumor tissue in response to extracellular ion-strength. For the trafficking of various cells or bacteria in an intact animal, we used optical imaging techniques or radiolabeled cells. We monitored tumor-targeting bacteria by bioluminescent imaging techniques, dentritic cells by radiolabeling and neuronal stem cells by sodium-iodide symporter reporter gene imaging. In summary, we introduced recent achievements of molecular nuclear imaging technologies in targeting receptors for hepatocyte or inflammatory cells and in trafficking bacterial, immune and stem cells using molecular nuclear imaging techniques.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10281-10287
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• 2015

Background: Development of a nanosized polymeric delivery system for erlotinib was the main objective of this research. Materials and Methods: Poly caprolactone-polyethylene glycol-polycaprolactone (PCEC) copolymers with different compositions were synthesized via ring opening polymerization. Formation of triblock copolymers was confirmed by HNMR as well as FT-IR. Erlotinib loaded nanoparticles were prepared by means of synthesized copolymers with solvent displacement method. Results: Physicochemical properties of obtained polymeric nanoparticles were dependent on composition of used copolymers. Size of particles was decreased with decreasing the PCL/PEG molar ratio in used copolymers. Encapsulation efficiency of prepared formulations was declined by decreasing their particle size. Drug release behavior from the prepared nanoparticles exhibited a sustained pattern without a burst release. From the release profiles, it can be found that erlotinib release rate from polymeric nanoparticles is decreased by increase of CL/PEG molar ratio of prepared block copolymers. Based on MTT assay results, cell growth inhibition of erlotinib has a dose and time dependent pattern. After 72 hours of exposure, the 50% inhibitory concentration (IC50) of erlotinib hydrochloride was appeared to be $14.8{\mu}M$. Conclusions: From the obtained results, it can be concluded that the prepared PCEC nanoparticles in this study might have the potential to be considered as delivery system for erlotinib.

• Journal of Pharmaceutical Investigation
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• v.32 no.4
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• pp.313-319
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• 2002

Rat skin permeation of various nonsteroidal antiinflammatory drugs (NSAIDs) was investigated in vitro using Franz diffusion cell at $37^{\circ}C$. The effect of various skin permeation enhancers was also observed as a preliminary study of developing transdermal delivery systems of NSAIDs. Lipophilicity of NSAIDs was determined from thε partition coefficient (log P) in 1-octanol/water and 1-octanol/IPB mutual-saturated solutions. The solubility was determined in water, isotonic phosphate buffer (IPB), and propylene glycol (PG) at $37^{\circ}C$. The rat skin permeation rate of acetaminophen, piroxicam, and aceclofenac was almost negligible, although they were saturated in PG. Addition of 1 % permeation enhancer increased the permeation rate of ketoprofen, ketorolac, and diclofenac. However, the skin permeation rate of ibuprofen did not increase with the addition of various enhancers. Among the permeation enhancers testεd, oleic acid was the most effective for various NSAIDs. Based on the daily dose, lipophilicity, and the skin permeation ratε achieved in this study, ketoprofen and ketorolac seem to be the most promising drug candidates for transdermal delivery systems, especially when formulated with unsaturated fatty acids, such as oleic acid.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.113-125
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• 2018

Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells. Theragnosis is a concept in next-generation medicine that simultaneously combines accurate diagnostics with therapeutic effects. Molecular components in exosomes have been found to be related to certain diseases and treatment responses, indicating that they may have applications in diagnosis via molecular imaging and biomarker detection. In addition, recent studies have reported that exosomes have immunotherapeutic applications or can act as a drug delivery system for targeted therapies with drugs and biomolecules. In this review, we describe the formation, structure, and physiological roles of exosomes. We also discuss their roles in the pathogenesis and progression of diseases including neurodegenerative diseases, cardiovascular diseases, and cancer. The potential applications of exosomes for theragnostic purposes in various diseases are also discussed. This review summarizes the current knowledge about the physiological and pathological roles of exosomes as well as their diagnostic and therapeutic uses, including emerging exosome-based therapies that could not be applied until now.

• Journal of Microbiology and Biotechnology
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• v.27 no.8
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• pp.1483-1490
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• 2017

In this study, silver nanoparticles (AgNPs) were synthesized by the citrate reduction process and, with the assistance of n-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, were successfully loaded with the macromolecular drug vancomycin (VAM) to form AgNP-VAM bioconjugates. The synthesized AgNPs, VAM, and AgNP-VAM conjugate were characterized by UV-visible spectroscopy, zeta potential analysis, confocal microscopy, and transmission electron microscopy. The effect of loading VAM onto AgNPs was investigated by testing the internalization of the bioconjugate into Mycobacterium smegmatis. After treatment with the AgNP-VAM conjugate, the bacterial cells showed a significant decrease in UV absorption, indicating that loading of the VAM on AgNPs had vastly improved the drug's internalization compared with that of AgNPs. All the experimental assessments showed that, compared with free AgNPs and VAM, enhanced internalization had been successfully achieved with the AgNP-VAM conjugate, thus leading to significantly better delivery of the macromolecular drug into the M. smegmatis cell. The current research provides a new potential drug delivery system for the treatment of mycobacterial infections.

• Proceedings of the KIEE Conference
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• 2004.07d
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• pp.2696-2698
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• 2004

Iontophoresis를 이용한 경피전달용 약물 패치를 제작하기 위해 고분자의 종류, 전류크기, 시간에 따른 약물방출 결과를 발표한다. 고분자 Hydroxy Propyl Methyl Cellulose(HPMC), Hydroxy Propyl Cellulose(HPC), Hydroxy Ethyl Cellulose(HEC)에 각각 국소마취제-Lidocaine을 넣어 시료를 제작하였다. 약물 방출은 Drug Delivery Cell(DDC)위에 Ag/AgCl 전극 (anode), Pt wire 전극(cathode)을 각각 설치하여 전압인가에 따른 이온 유동으로부터 시간에 따른 전압/전류변화 및 약물농도를 고찰하였다. 전압 15V 인가 시 고분자 막과 전해질 사이에 흐르는 전류 1.0mA는 15분간 유지되지만, Ag/AgCl 전극의 산화작용으로 인해 전류는 서서히 감소하며 26분 후 거의 흐르지 않았다. 따라서 안정적인 전류로 유지되는 시간을 15분으로 최적화하였다. 고분자 중 HPMC 막을 사용하여 약물방출 실험을 한 경우 UV 분석결과 파장 262.26nm에서 최대 흡광도 0.238이었고, 가장 높은 약물농도가 나타났다. 이러한 HPMC의 약물방출 실험결과 비교적 높은 전류 1.0mA일 때 약물 방출량이 많았고, 동일한 전류 0.4mA를 장시간 흐르게 하였을 경우, 농도가 축적되므로 치료 가능한 안정적인 특성임을 확인하였다.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7113-7118
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• 2014

Background: HSP90 may be overexpressed in cancer cells which are greatly dependent on Hsp90 function. Geldanamycin derivative 17 allylamino-17-demethoxygeldanamycin (17-AAG) inhibits the function and expression of HSP90. 17-AAG has poor water-solubility which is a potential problem for clinical practice. In this study for improving the stability and solubility of molecules in drug delivery systems we used a ${\beta}$-cyclodextrin-17AAG complex. Materials and Methods: To assess cytotoxic effects of ${\beta}$-cyclodextrin-17AAG complexes and free 17AAG, colorimetric cell viability (MTT) assays were performed. Cells were treated with equal concentrations of ${\beta}$-cyclodextrin- 17AAG complex and free 17AAG and Hsp90 gene expression levels in the two groups was compared by real-time PCR. Results: MTT assay confirmed that ${\beta}$-cyclodextrin- 17AAG complex enhanced 17AAG cytotoxicity and drug delivery in T47D breast cancer cells. The level of Hsp90 gene expression in cells treated with ${\beta}$-cyclodextrin- 17AAG complex was lower than that of cells treated with free 17AAG (P=0.001). Conclusions: The results demonstrated that ${\beta}$-cyclodextrin- 17AAG complexes are more effective than free 17AAG in down-regulating HSP90 expression due to enhanced ${\beta}$-cyclodextrin-17AAG uptake by cells. Therefore, ${\beta}$-cyclodextrin could be superior carrier for this kind of hydrophobic agent.

• Bulletin of the Korean Chemical Society
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• v.35 no.8
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• pp.2290-2294
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• 2014

For the present study, rhEGF was encapsulated into solid lipid nanoparticles (SLNs). The SLNs were prepared by the $W_1/O/W_2$ double emulsification method combined with the high pressure homogenization method and the physical properties such as particle size, zeta-potential and encapsulation efficiency were measured. The overall particle morphology of SLNs was investigated using a transmission electron microscopy (TEM). The percutaneous skin permeation and accumulation property of rhEGF was evaluated using Franz diffusion cell system along with confocal laser scanning microscopy (CLSM). The mean particle size of rhEGF-loaded SLNs was $104.00{\pm}3.99nm$ and the zeta-potential value was in the range of -$36.99{\pm}0.54mV$, providing a good colloidal stability. The TEM image revealed a spherical shape of SLNs about 100 nm and the encapsulation efficiency was $18.47{\pm}0.22%$. The skin accumulation of rhEGF was enhanced by SLNs. CLSM image analysis provided that the rhEGF rat skin accumulation is facilitated by an entry of SLNs through the pores of skin.