• Macromolecular Research
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• 제17권1호
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• pp.19-25
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• 2009

In order to enhance the gene delivery efficiency and decrease the cytotoxicity of polyplexes, we synthesized Solutol-g-PEI by conjugating polyethyleneimine (PEI) to Solutol (polyoxyethylene (10) stearate), and evaluated its efficiency as a possible nonviral gene carrier candidate. Structural analysis of synthesized polymer was performed by using $^1H$-NMR. Gel retardation assay, particle sizes and zeta potential measurement confirmed that the new gene carrier formed a compact complex with plasmid DNA. The complexes were smaller than 150 nm, which implicated its potential for intracellular delivery. It showed lower cytotoxicity in three different cell lines (Hela, MCF-7, and HepG2) than PEI 25 kDa. pGL3-lus was used as a reporter gene, and the transfection efficiency was in vitro measured in Hela cells. Solutol-g-PEI showed much higher transfection efficiency than unmodified PEI 25 kDa.

• Korean Chemical Engineering Research
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• 제45권5호
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• pp.493-499
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• 2007

본 연구에서는 UV photo-lithography 방식의 particle replication in non-wetting templates(PRINT) 법을 이용하여 약물 전달에 운반체로 사용되는 $3{\mu}m{\times}3{\mu}m{\times}2{\mu}m$ 사이즈의 균일한 고분자 하이드로젤 입자를 제조하였다. 몰드(mold)와 기재(substrate)는 PRINT 방식을 통하여 탄성을 지닌 perfluoropolyethers(PFPE)로 제작하였으며 이를 반복적으로 사용할 수 있도록 하였다. 제작된 입자는 점착성이 있는 수용성 고분자를 이용하여 회수하였다. 입자의 주요 성분은 생분해성 고분자인 poly(ethylene glycol) diacrylate(PEG-diA)이며, 세포 uptake에 적합하도록 aminoethylacrylate(AEM)와 2-acryloxyethyltrimethyl ammonium chloride(AETMAC)를 첨가하였다. 본 연구를 통해 균일하고 원하는 크기의 생체분해성 고분자 입자를 제작하는 PRINT 기술이 약물 전달 및 유전자 전달에 필요한 수송체인 비바이럴 벡터를 제작하기 위한 효과적인 기술임을 제시하였다.

• Bulletin of the Korean Chemical Society
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• 제22권1호
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• pp.46-52
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• 2001

To evaluate the non-ionic polymer, poly(ethylene glycol) (PEG), as a component in cationic copolymers for non-viral gene delivery systems, PEG was coupled to polyethylenimine (PEI). We present the effects of different degrees and shapes of pegylation of PEI on cytotoxicity, water solubility and transfection efficiency. This work reports the synthesis and characterization of a series of cationic copolymers on the basis of the conjugates of PEI with PEG. The modified molecules were significantly less toxic than the original polymer. Moreover, the chemical modification led to enhancement of their solubility. The comparison of pegylated PEIs with different degrees of derivation showed that all the polymers tested reached comparable levels of transgene expression to that of native PEI. As assessed by agarose gel electrophoresis, even highly substituted PEI derivatives were still able to form polyionic complexes with DNA. However, aside from an increase in solubility and retention of the ability to condense DNA, methoxy-PEG-modified PEIs resulted in a significant decrease in the transfection activity of the DNA complexes. In fact, the efficiency of the copolymer was compromised even at a low degree of modification suggesting that the PEG action resulting from its shape is important for efficient gene transfer. The mode of PEG grafting and the degree of modification influenced the transfection efficiency of PEI.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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)

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.277.2-278
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• 2002

Synthetic vectors have been considered as a safer and more versatile alternative to viral-based gene delivery systems. A variety of simple synthetic vector systems such as cationic lipid- and polymer-complexed plasmid DNA were shown to have a significant transfection activity in vitro but their use in vivo has been hampered by the decrease in transfection efficiency mediated by non-specific electrostatic interactions with serum components. (omitted)

• Macromolecular Research
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• 제14권2호
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• pp.129-131
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• 2006

• Journal of Pharmaceutical Investigation
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• 제33권4호
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• pp.261-265
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• 2003

Tumor necrosis facto-related apoptosis-inducing ligand (TRAIL) is a recently identified member of the tumor necrosis factor cytokine superfamily. TRAIL has been shown to induce apoptosis in a number of tumor cells whereas cells from most of normal tissues are highly resistant to TRAIL-induced apoptosis. These observations have raised considerable interest in the use of TRAIL in tumor therapy. In this study we report the biodistribution fates and serum expression pattern of plasmid DNA encoding TRAIL (pTRAIL) delivered in erythrocyte ghosts (EG). pTRAIL was loaded into EG by electroportion in a hypotonic medium The mRNA expression of pTRAIL was prolonged following delivery in EG-encapsulated forms. EG containing pTRAIL showed significant levels of mRNA expression in the blood over 9 days. The organ expression patterns of pTRAIL delivered via EG, however, did not significantly differ from those of naked pTRAIL, indicating that the expression-enhancing effect of EG containing pTRAIL was localized to the blood. These results suggest that pTRAIL-loaded EG might be of potential use in the treatment of hematological diseases such as TRAIL-sensitive leukemia.

• 한국고분자학회:학술대회논문집
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• 한국고분자학회 2006년도 IUPAC International Symposium on Advanced Polymers for Emerging Technologies
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• pp.44-45
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• 2006

Gene therapy holds great promise for treating various forms of diseases with a genetic origin including cystic fibrosis, different forms of cancer, and cardiovascular disorders. The clinical use of gene therapy treatments is however restricted, mainly because of the absence of safe and efficient gene delivery technologies. In our group, with an aim of developing efficient and nontoxic polymeric gene delivery systems, several novel types of polymeric gene carriers have been designed, synthesized, and evaluated. Herein, I will mainly present our recent work on low molecular weight linear PEI-PEG-PEI triblock copolymers, degradable hyperbranched poly(ester amine)s, and reduction-sensitive poly(amido amine)s.

• Archives of Pharmacal Research
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• 제28권6호
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• pp.722-729
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• 2005

With the aim to improve the specificity and to reduce the cytotoxicity of polyethylenimine (PEI), we have synthesized the conjugates of the branched PEI (25 kDa) with transferrin. The trans-ferrin-PEI (TP) conjugates with five compositions were synthesized using periodate oxidation method and confirmed by FT-IR spectroscopy and gel permeation chromatography. The free amine contents of TP conjugates, which were able to condense and deliver DNA, increased as the amount of PEI increased. TP/DNA polyplexes were characterized by measuring gel elec-trophoresis, ethidium bromide fluorescence quenching, particle size and zeta potential of complexes. Complete complexation of the polyplexes was observed above the N/P ratio of 5 in TP/DNA, and above 3 in PEI/DNA, respectively. The zeta potential of the complexes decreased as the amount of transferrin in TP conjugates increased. Transfection efficiency of TP conjugates was evaluated in HeLa cell and Jurkat cell systems. Among the five compositions of TP conjugates, TP-2 system mediated a higher $\beta$-galactosidase gene expression than PEI system in Jurkat cell which was known to express elevated numbers of transferrin receptors. From the results of the cell viability based on MTT assay, TP conjugates showed lower cytotoxicity com-pared with the PEI system. We expect that the TP conjugate can be used efficiently as a non-viral gene delivery vector.

• 한국미생물·생명공학회지
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• 제34권4호
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• pp.329-334
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• 2006

콜레스테롤 유래의 양이온성 리피드 2-aminoethylcarbamate-cholesterol(Chol-E)를 합성하여 이의 리포좀을 제조하였다. 리포좀은 다양한 비율로 중성지방인 DOPE와 섞어서 만든 후 $100{\sim}200nm$의 membrane으로 extrusion시켜 균일한 리포좀을 제작하여 크기 및 전위를 측정하였다. 형광단백질 및 luciferase plasmid의 발현을 여러가지 세포에서 확인한 결과 우수한 발현양상을 보였으며 혈청이 있는 조건에서도 발현이 증가임을 볼수 있었으며, 합성 ODNs의 전달도 adipocyte cell 에서도 잘 이루어지는 것을 확인할 수 있었다 임상실험에 쓰이는 저독성의 DC-chol에 비교하여도 독성이 적은 리포좀임을 알 수 있으며 혈청하에서도 안정하게 유전자를 전달할 수 있는 응용성이 기대되는 새로운 리포좀을 제조하였음을 알 수 있다.