a McColl-Lockwood Laboratory for Muscular Dystrophy Research, Carolinas Medical Center , Charlotte , NC , USA.
Drug Deliv. 2016 Nov;23(9):3224-3233. doi: 10.3109/10717544.2016.1162877. Epub 2016 Mar 29.
A series of poly (ester amines) (PEAs) constructed from low molecular weight polyethyleneimine (LPEI, Mw: 0.8k, 1.2k Da) and Pluronic (different molecular weight (Mw) and hydrophilic-lipophilic-balance (HLB)) components were synthesized, and evaluated in vitro and in vivo as gene delivery carriers. Most PEA polymers were able to bind and condense plasmid DNA effectively into particles of approximately 150 nm in solution at the polymer/DNA ratio of 5 and above. Transfection efficiency of the PEA polymers depends on particle size of the polymer/DNA complex, molecular weight and HLB of the Pluronics and the size of PEI within PEA composition, as well as the cell type. Significant improvement in gene delivery efficacy was achieved with PEA01/04/05 composed of Pluronic size (Mw: 3000-5000 Da), and HLB (12-18) in CHO, C2C12 and HSkM cell lines; and the effective transfection was reflected with PEA 01/04/07 composed of Pluronics with size (2000-5000 Da) and HLB (12-23) in mdx mice. The best formulation for pDNA delivery was obtained with PEA 01 producing transgene expression efficiency 5, 19-folds of that of PEI 25k in vitro and in vivo, respectively. These results potent some of these PEA polymers as attractive vehicles for gene or oligonucleotide delivery.
一系列由低分子量聚乙烯亚胺（LPEI，Mw：0.8k，1.2kDa）和泊洛沙姆（不同分子量（Mw）和亲水-亲脂平衡（HLB））组成的聚（酯胺）（PEAs）被合成，并在体外和体内作为基因传递载体进行了评估。大多数 PEA 聚合物能够有效地将质粒 DNA 结合并凝聚成溶液中约 150nm 的颗粒，聚合物/DNA 比例在 5 及以上。PEA 聚合物的转染效率取决于聚合物/DNA 复合物的粒径、泊洛沙姆的分子量和 HLB 以及 PEA 组成中 PEI 的大小以及细胞类型。PEA01/04/05 由分子量（Mw：3000-5000Da）和 HLB（12-18）的泊洛沙姆组成，在 CHO、C2C12 和 HSkM 细胞系中显著提高了基因传递效率；而 PEA01/04/07 由分子量（2000-5000Da）和 HLB（12-23）的泊洛沙姆组成，在 mdx 小鼠中则表现出有效的转染。PEA01 用于 pDNA 传递的最佳配方，其转染效率在体外和体内分别是 PEI25k 的 5 倍和 19 倍。这些结果表明，这些 PEA 聚合物中的一些具有作为基因或寡核苷酸传递的有吸引力的载体的潜力。
