Polymeric nano-particular and micellar gene delivery systems for gene therapy = 유전자 치료를 위한 고분자 나노 입자와 미셀 형태의 유전자전달 시스템

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A series of linear poly(ethylenimine) (L-PEI) containing varying amounts of cationic charge density in its backbone was produced by controlled hydrolysis of poly(2-ethyl-2-oxazoline) (PEtOz) for using as a nonviral DNA transfection agent. The effects of cationic charge density and molecular weight of the L-PEI on the cytotoxicity and transfection efficiency were studied. Highly compacted L-PEI/DNA complex (~150 nm) was obtained with a surface charge value of around +28.4 mV. Cell cytotoxicity was affected to a great extent by the hydrolysis percent of L-PEI as well as by the molecular weight. Transfection efficiency of luciferase plasmid DNA against NIH 3T3 fibroblast was largely dependent upon the hydrolysis percent (charge density) in the polymer backbone and the molecular weight of the L-PEI, but independent of the total amount of cationic charges used for DNA condensation. Poly(lactic-co-glycolic acid) [PLGA] grafted poly(L-lysine) [PLL] (PLL-g-PLGA) was synthesized to demonstrate its micelle-forming property in an aqueous solution. The micelles were used as a gene delivery carrier. The hydrodynamic diameter of PLL-g-PLGA micelles in an aqueous solution was ca. 149 nm with a narrow size distribution. Critical micelle concentration (cmc) was 9.6 mg/L. The PLL-g-PLGA micelles could be used to produce compact nanoparticulate complexes with plasmid DNA, which could efficiently protect the complexed DNA from enzymatic degradation by DNase I. The micelle/DNA complexes had highly compacted structure sized between 200 - 300 nm with a positive surface charge value. The PLL-g-PLGA micelles exhibited much higher transfection efficiency with lower cytotoxicity than PLL. Biodegradable poly(D,L-lactic-co-glycolic acid) [PLGA] was chemically conjugated to oligonucleotide (ODN) to form an amphiphatic structure which is similar to an A-B type block copolymer. The ODN/PLGA conjugates self-assembled in aqueous solution to form a micellar structure by serving PLGA segments as ...
Park, Tae-Gwanresearcher박태관researcher
한국과학기술원 : 생물과학과,
Issue Date
231018/325007  / 000995346

학위논문(박사) - 한국과학기술원 : 생물과학과, 2003.8, [ xiii, 108 p. ]


nanoparticle; micelle; polymeric carrier; gene therapy; gene delivery; 유전자전달; 나노입자; 미셀; 고분자 전달체; 유전자치료

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