Reconstitutable charged polymeric (PLGA)(2)-b-PEI micelles for gene therapeutics delivery.
Reconstitutable charged polymeric (PLGA)(2)-b-PEI micelles for gene therapeutics delivery.
复制标题
DOI：
10.1016/j.biomaterials.2011.01.077
复制
发表时间：
2011-05
期刊：
影响因子：
14
通讯作者：
Bae, You Han
中科院分区：
文献类型：
--
作者：
Mishra, Deepa;Kang, Han Chang;Bae, You Han
关键词：
这项研究探讨了创造一种基于带电聚合物胶束的核酸递送系统的可能性，这种递送系统可以通过添加水来轻松地重组。合成了(PLGA36 KDa)2-b-bPEI25 kDa(PLGA MW 36 kDa，bPEI MW 25 kDa，PLGA：bPEI嵌段比=2)，并将其用于阳离子胶束的制备。该共聚物在内质体pH范围内保留了来自bPEI块的质子缓冲能力。胶束/PDNA复合体重组后保持其颗粒大小(100-150 nm)和表面电荷(30-40 mV)。结果发现，加入少量低分子量的bPEI(1.8 kDa)可完全屏蔽胶束/PDNA复合体中的PDNA，使新鲜和重组复合体的转染率提高50-100倍，而不影响复合体的大小。“重组”胶束/pDNA/bPEI1.8 kDa(WR-1)复合体的转染率是“新鲜”复合体的16倍。尽管“重组”胶束/PDNA/bPEI1.8 kDa复合体的转染率比对照“新鲜”bPEI25 kDa/PDNA(N/P5)复合体低3.6倍，但转染率却比“重组”bPEI25 kDa/PDNA(N/P5)复合体高39倍。胶束/pDNA/bPEI1.8μ体系对MCF7细胞具有很低的细胞毒作用，且随着pDNA剂量的增加，转染率呈线性增加。这些结果表明，这种基于PLGA-b-bPEI聚合物胶束的系统非常适合作为可重组的基因递送系统，并具有作为基因治疗应用的递送系统的高潜力。
This study investigated the potential of creating a charged polymeric micelle-based nucleic acid delivery system that could easily be reconstituted by the addition of water. (PLGA36kDa)2-b-bPEI25kDa (PLGA MW 36kDa, bPEI Mw 25kDa, PLGA:bPEI block ratio = 2) was synthesized and used to prepare cationic micelles. The copolymer retained proton-buffering capability from the bPEI block within the endosomal pH range. Micelle/pDNA complexes retained their particle size (100–150 nm) and surface charge (30–40 mV) following reconstitution. It was found that adding a small amount of low molecular weight bPEI (1.8 kDa) completely shielded pDNA in the micelle/pDNA complexes and enhanced transfection efficiency 50–100 fold for both fresh and reconstituted complexes without affecting complex size. Transfection efficiency for “reconstituted” micelle/pDNA/bPEI1.8kDa (WR 1) complexes was 16-fold higher than its “fresh” counterpart. Although transfection levels achieved using “reconstituted” micelle/pDNA/bPEI1.8kDa complexes were 3.6-fold lower than control “fresh” bPEI25kDa/pDNA (N/P 5) complexes, transfection levels were 39-fold higher than “reconstituted” bPEI25kDa/pDNA (N/P 5) complexes. The micelle/pDNA/bPEI1.8kDa system showed very low cytotoxicity in MCF7 cells even with pDNA doses up to 20 μg, and transfection levels increased linearly with increasing pDNA dose. These results indicate that this PLGA-b-bPEI polymeric micelle-based system is well suited as a reconstitutable gene delivery system, and has high potential for use as a delivery system for gene therapy applications.
登录
查看更多内容
影响因子：
14
作者：
Kang, Han Chang;Kang, Ho-Jung;Bae, You Han
通讯作者：
Bae, You Han
影响因子：
3.3
作者：
Collier, Jarrod W.;Shah, Rakhi B.;Khan, Mansoor A.
通讯作者：
Khan, Mansoor A.
DOI：
10.1093/gerona/glq018
发表时间：
2010-04-01
影响因子：
5.1
作者：
Louis, Audreen;Bartke, Andrzej;Masternak, Michal M.
通讯作者：
Masternak, Michal M.
影响因子：
12.4
作者：
Beer, Shelly;Bellovin, David I.;Grimm, Dirk
通讯作者：
Grimm, Dirk
DOI：
10.1016/j.ejpb.2009.02.002
发表时间：
2009-06-01
影响因子：
4.9
作者：
Holzer, Melisande;Vogel, Vitali;Langer, Klaus
通讯作者：
Langer, Klaus