• Proceedings of the PSK Conference
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• 2003.10b
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• pp.226.3-227
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• 2003

A cationic lipid emulsion (o/w) containing lipiodol and 1, 2-dioleoyl-sn- glycero-3-trimethylammonium-propane (DOTAP) has been prepared as a gene delivery system. In order to increase the transfection efficiency of the lipiodol emulsion, 1 2-dioleoyl-sn-glycero-3-phospho-ethanolamine (DOPE) and polyoxyethylene sorbitan monooleate (Tween 80) were incorporated as additional lipids. By including DOPE and Tween 80, the cationic emulsion became a more potent gene carrier under in vitro condition in the presence of serum, and under in vivo condition. (omitted)

• Journal of Pharmaceutical Investigation
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• v.40 no.spc
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• pp.33-43
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• 2010

Hyaluronic acid (HA) is a biodegradable, biocompatible, non-toxic, non-immunogenic and non-inflammatory linear polysaccharide, which has been used for various medical applications including arthritis treatment, wound healing, ocular surgery, and tissue augmentation. Because of its mucoadhesive property and safety, HA has received much attention as a tool for drug delivery system development. It has been used as a drug delivery carrier in both nonparenteral and parenteral routes. The nonparenteral application includes the ocular and nasal delivery systems. On the other hand, its use in parenteral systems has been considered important as in the case of sustained release formulation of protein drugs through subcutaneous injection. Particles and hydrogels by various methods using HA and HA derivatives as well as by conjugation with other polymer have been the focus of many studies. Furthermore, the affinity of HA to the CD44 receptor which is overexpressed in various tumor cells makes HA an important means of cancer targeted drug delivery. Current trends and development of HA as a tool for drug delivery will be outlined in this review.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.277.1-277.1
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• 2002

The purpose of this study was to develop PEl-based gene carriers with optimal serum stability and reduced cytotoxicity. PEl is an efficient gene transfer agent with the ability of DNA condensation and endosome escape: however; use of the polymer in vivo is hampered by signigicant reduction in transfection activity by the presence of serum. Chitosan is a non-toxic. biodegradable and biocompatible polymer with hydrophilic functional groups so it may provide a physical stability against challenge by serum proteins. (omitted)

• Molecules and Cells
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• v.22 no.2
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• pp.175-181
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• 2006

Delivery of DNA vaccines to airway mucosa would be an ideal method for mucosal immunization. However, there have been few reports of a suitable gene delivery system. In this study we used a cationic emulsion to immunize mice via the intranasal route with pCMV-S coding for Hepatitis B virus surface antigen (HBsAg). Complexing pCMV-S with a cationic emulsion dramatically enhanced HBsAg expression in both nasal tissue and lung, and was associated with increases in the levels of HBs-specific Abs in serum and mucosal fluids, of cytotoxic T lymphocytes (CTL) in the spleen and cervical and iliac lymph nodes, and of delayed-type hypersensitivity (DTH) against HBsAg. In contrast, very weak humoral and cellular immunities were observed following immunization with naked DNA. In support of these observations, a higher proliferative response of spleenocytes was detected in the group immunized with the emulsion/pCMV-S complex than in the group immunized with naked pCMV-S. These findings may facilitate development of an emulsion-mediated gene vaccination technique for use against intracellular pathogens that invade mucosal surfaces.

• Polymer(Korea)
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• v.33 no.3
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• pp.213-218
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• 2009

A cationic lipid emulsion containing 1,2-dioleoyl-3-trimethylammonium-propane(DOTAP), Tween80, squalene has been prepared as a gene delivery system. In order to increase the transfection efficiency of gene carrier, folate was used as the tumor-targeting ligand that was attached on PEG-DPPE. HeLa and 293 cells were used for the in vitro transfection experiment. HeLa cell is a folate-positive cell line. The mean particle sizes of polymeric lipid system and DNA/lipid complex system were 206.6 nm and 150.5 nm, respectively. The transfection efficiencies of our carriers(4:l(w:w) complex ratio)were 100 times higher than that of DOTAP only emulsion due to the targeting effect of folate.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.185-190
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• 2001

Human papillomavirus (HPV) infection is known to cause cervical cancers. Human papillomavirus-like particles (VLP) have been studied as preventive vaccines of cervical cancers. To develop VLP as a therapeutic gene carrier, we studied the method to encapsulate cytokine genes in virus-like particles. HPV type 16 capsid L1 genes were amplified by polymerase chain reaction and cloned into T vector. L1 gene was then inserted into baculovirus transfer vector. The clone of baculovirus encoding L1 gene was isolated and used to express L1 protein in Sf 21 insect cells. VLP were purified by CsCl density gradient and ultracentrifugation. VLP were disassembled to capsomer units by treatment of a reducing agent. Given that interleukin-2 (IL-2) genes have been used in anticancer gene therapy and as a molecular adjuvant, IL-2 cytokine plasmids were chosen as a model gene. IL-2 plasmids were incubated with the disassembled capsomer suspension. To reassemble the particles, the mixture of capsomers and cytokine plasmids was dialyzed. The disassembly and reassembly of VLP were confirmed by transmission electron microscopy. The entrapment of cytokine plasmids in reassembled VLP was tested by the stability of plasmids against DNase I. After treatment of reassembled virus-like particles with DNase I, discrete IL-2 DNA band was observed. Our results indicate that IL-2 cytokine plasmid (3.5 kb size) can be encapsulated in the virus-like particles, suggesting the potential of VLP as a gene delivery system. Moreover, VLP containing the adjuvant cytokine plasmids might function as more effective subunit vaccines.

• Polymer(Korea)
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• v.38 no.1
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• pp.43-48
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• 2014

In this paper, we made a new polycationic polymeric liposome composed of low molecular weight polyethylenimine (PEI) and 10,12-pentacosadiynoic acid (PCDA). PCDA liposome was prepared by ultraviolet irradiation. PEI was further conjugated on the surface of the polymerized PCDA liposome using coupling reagents to make PCDA-PEI. The blue-to-red transition of PCDA liposome was observed during the coupling reaction. The size distribution of liposome and complexes with plasmid DNA was measured by dynamic light scattering (DLS). The complex formation was also identified by agarose gel electrophoresis and PicoGreen reagent assay. We confirmed the complex formation of the polymeric liposome with DNA and then performed transfection and cytotoxicity assay in HEK 293 and HeLa cells. As a result, PCDA-PEI showed significant gene transfection efficiency and low cytotoxicity. This study shows that PEI-conjugated PCDA liposome could be an efficient gene or drug delivery carrier.

• Archives of Pharmacal Research
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• v.27 no.12
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• pp.1284-1289
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• 2004

Galactosylated chitosan-graft-poly(vinyl pyrrolidone) (GCPVP) was synthesized and characterized for hepatocyte-targeting gene carrier. GCPVP itself as well as GCPVP/DNA complex had negligible cytotoxicity regardless of the concentration of GCPVP and the charge ratio, but GCPVP/DNA complex had slightly cytotoxic effect on HepG2 cells only in the case of the higher charge ratio and 20 mM of $Ca^{2+}$ concentration used. Through the confocal laser scanning microscopy, it is shown that the endocytosis by interaction between galactose ligands of GCPVP and ASGPR of the hepatocytes was the major route of transfection of GCPVP/F-plasmid complexes.

• Bulletin of the Korean Chemical Society
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• v.30 no.4
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• pp.897-901
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• 2009

Heme oxygenase-1 (HO-1) is an anti-inflammatory and anti-apoptotic protein and has been applied to various gene therapy researches. However, constitutive expression of HO-1 may induce deleterious side effects. In this research, hypoxia inducible HO-1 expression plasmid, pEpo-SV-HO-1, was constructed with the erythropoietin (epo) enhancer and simian virus 40 (SV40) promoter to avoid these unwanted side effects. Dexamethasone conjugated polyethylenimine (PEI-Dexa) was used as a gene carrier. It was previously reported that dexamethasone protected cardiomyocytes from apoptosis under hypoxia. In this research, PEI-Dexa reduced the caspase-3 level in hypoxic H9C2 cardiomyocytes as a derivative of dexamethasone, suggesting that PEI-Dexa is an anti-apoptotic reagent as well as a gene carrier. pEpo-SV-HO-1 was transfected to H9C2 cardiomyocytes using PEI-Dexa and the cells were incubated under normoxia or hypoxia. HO-1 expression was induced in the pEpo-SV-HO-1 transfected cells under hypoxia. In addition, cell viability under hypoxia was higher in the pEpo-SV-HO-1 transfected cells than the pEpo-SV-Luc transfected cells. Also, caspase-3 level was reduced in the pEpo-SV-HO-1 transfected cells under hypoxia. In addition to the anti-apoptotic effect of PEI-Dexa, hypoxia inducible HO-1 expression by pEpo-SVHO- 1 may be helpful to protect cardiomyocytes under hypoxia. Therefore, pEpo-SV-HO-1/PEI-Dexa complex may be useful for ischemic heart disease gene therapy.

• Journal of Life Science
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• v.28 no.4
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• pp.496-507
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• 2018

Immunization has been performed for centuries and is generally accepted as a sustainable method of controlling bacteria, viruses, and mediated and infectious diseases. Despite many studies having been performed on animal subjects to demonstrate the importance of toxin immunity, the use of toxoid vaccines in humans and animals has been limited for a long time. Recently, the development of the toxoid antigen delivery system has been facilitated using novel nano-medicinal technology. The micro/nano-carrier has been used to improve vaccination coverage as well as reduce vaccine costs. A micro/nano-carrier is a micro/nano-sized material that delivers immune cargo, including recombinant or peptide toxoid antigens. These toxoid antigens are either encapsulated in the interior or displayed on the surface of micro/nano-carriers as a way to protect them from the cellular machinery. In particular, the combination of toxoid antigens and micro/nano-carriers can induce phagocytosis through the specific interactions between GCs and macrophages; thus, the toxoid antigens can be delivered easily into the macrophages. This paper reviews recent achievements of micro/nano-carriers in the field of vaccine delivery systems such as microbial ghost cells (GCs, Bacterial ghost cells and Yeast ghost cells), gene-manipulated outer membrane vesicles (OMVs) and biocompatible, polymer-based nanoparticles (NPs, NP-Carrier and NP-Cage). Finally, this review shows various aspects in terms of the hosts' immune responses.