Biodegradable polyester, poly[α-(4 aminobutyl)-L-glycolic acid], as a non-toxic gene carrier

被引:148
作者
Lim, YB
Han, SO
Kong, HU
Lee, Y
Park, JS
Jeong, B
Kim, SW
机构
[1] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Ctr Controlled Chem Delivery, BPRB, Salt Lake City, UT 84112 USA
[2] Seoul Natl Univ, Sch Chem & Mol Engn, Seoul 151742, South Korea
基金
新加坡国家研究基金会;
关键词
PAGA; gene delivery; biodegradable; ester linkage; non-toxic gene carrier; controlled release;
D O I
10.1023/A:1007552007765
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Purpose. The aim of this study was to develop a non-toxic polymeric gene carrier For this purpose, biodegradable cationic polymer, poly[alpha-(4-aminobutyl)-L-glycolic acid] (PAGA) was synthesized. PAGA was designed to have ester linkage because polyesters usually show biodegradability. Methods. Degradation of PAGA in an aqueous solution was followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). PAGA/DNA complexes were characterized by gel electrophoresis, atomic force microscopy (AFM), dynamic light scattering (DLS). The transfection was measured by using the: beta-galactosidase reporter gene. Results. PAGA was degraded in aqueous solution very quickly and the final degradation product was a monomer (L-oxylysine). Formation of self-assembling biodegradable complexes between PAGA and DNA at a charge ratio 1:1 (+/-) was confirmed by gel band shift assay and AFM. In these studies, controlled release of DNA from the complexes could be seen. The complexes showed about 2-fold higher transfection efficiency than DNA complexes of poly-L-lysine (PLL), a structural analogue of PAGA, which is the most commonly used poly-cation for gene delivery. The polymer did not show cytotoxicity, possibly because of its degradability and the biocompatibility of the monomer. Conclusions. The use of the biodegradable poly-cation, PAGA, as a DNA condensing agent will be useful in safe gene delivery.
引用
收藏
页码:811 / 816
页数:6
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