Controlled release of plasmid DNA from a genetically engineered silk-elastinlike hydrogel

Controlled release of plasmid DNA from a genetically engineered silk-elastinlike hydrogel
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DOI:
10.1023/a:1016406120288
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发表时间:
2002-07-01
影响因子:
3.7
通讯作者:
Ghandehari, H
Ghandehari, H
中科院分区:
医学3区
文献类型:
--
作者:
Megeed, Z;Cappello, J;Ghandehari, H

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目的。本研究的目的是评价一种基因工程弹性丝样聚合物(SELP)作为质粒dna控释基质的潜力。考察了SELP浓度、DNA浓度、SELP固化时间和缓冲离子强度对SELP水凝胶中DNA释放的影响。为了计算水凝胶内DNA的平均有效扩散率,将释放数据拟合到已知方程。DNA通过离子交换机制从SELP水凝胶中释放出来。在所研究的条件下,释放速度受缓冲离子强度、SELP浓度和SELP固化时间的影响,但不受DNA浓度的影响。pRL-CMV质粒DNA在SELP水凝胶中的表观扩散率为3.78 +/- 0.37 × 10(-)10 cm(2)/s(含12% w/w SELP水凝胶,固化4 h)至4.69 +/- 2.81 × 10(-)9 cm(2)/s(含8% w/w SELP水凝胶,固化1 h)。利用重组技术精确定制selp的结构和物理化学性质的能力,加上它们形成可注射的、释放DNA的原位水凝胶仓库的能力,使这类聚合物成为进一步评估受控基因传递的有趣候选物。
Purpose. The purpose of this study was to evaluate the potential of a genetically engineered silk-elastinlike polymer (SELP) as a matrix for the controlled release of plasmid DNA.Methods. The influences of SELP concentration, DNA concentration, SELP cure time, and buffer ionic strength on the release of DNA from SELP hydrogels were investigated. To calculate the average effective diffusivity of DNA within the hydrogels, the release data were fitted to a known equation.Results. DNA was released from SELP hydrogels by an ion-exchange mechanism. Under the conditions studied, the release rate was influenced by buffer ionic strength, SELP concentration, and SELP cure time but not DNA concentration. The apparent diffusivity of pRL-CMV plasmid DNA in SELP hydrogels ranged from 3.78 +/- 0.37 x 10(-)10 cm(2)/s (for hydrogels containing 12% w/w SELP and cured for 4 h) to 4.69 +/- 2.81 x 10(-)9 cm(2)/s (for hydrogels containing 8% w/w SELP and cured for 1 h).Conclusions. The ability to precisely customize the structure and physicochemical properties of SELPs using recombinant techniques, coupled with their ability to form injectable, in situ hydrogel depots that release DNA, renders this class of polymers an interesting candidate for further evaluation in controlled gene delivery.