In vitro and in vivo release of albumin using a biodegradable MPEG-PCL diblock copolymer as an in situ gel-forming carrier
In vitro and in vivo release of albumin using a biodegradable MPEG-PCL diblock copolymer as an in situ gel-forming carrier
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DOI：
10.1021/bm060991u
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发表时间：
2007-04-01
影响因子：
6.2
通讯作者：
Lee, Hai Bang
中科院分区：
文献类型：
--
作者：
Hyun, Hoon;Kim, Yu Han;Lee, Hai Bang
合成了MPEG-PCL二嵌段共聚物作为原位凝胶载体，并研究了其在水溶液中的相转变行为。为了比较，还研究了Pluronic F-127的水溶液，一种广泛使用的可注射凝胶形成溶液。MPEG-PCL共聚物和Pluronic水溶液在室温下均为溶胶。随着温度升高至室温以上，二嵌段共聚物和Pluronic溶液经历溶胶-凝胶相变，其表现为粘度增加，表明形成凝胶。所有的共聚物溶液在体温下变成凝胶，尽管凝胶粘度随着溶液中MPEG-PCL二嵌段共聚物的浓度增加而增加。在将凝胶暴露于PBS的体外实验中，MPEG-PCL凝胶保持其结构完整性超过28天，而Pluronic凝胶在2天内消失。当将聚合物溶液皮下注射到大鼠中时，观察到相同的结果。MPEG-PCL凝胶保持其结构完整性超过30天，而Pluronic凝胶在2天后不能观察到。通过测定异硫氰酸荧光素标记的牛血清白蛋白（BSA-FITC）从MPEG-PCL二嵌段共聚物凝胶中的体外和体内释放，研究了凝胶作为药物载体的能力。在体外，BSA释放持续超过20天，在较低的二嵌段共聚物浓度下释放更大;相比之下，Pluronic凝胶在1天内几乎完全释放BSA-FITC。当将BSA-FITC负载的二嵌段共聚物和Pluronic溶液皮下注射到大鼠中时，它们立即转化为凝胶。在体内，从MPEG-PCL凝胶中观察到BSA-FITC持续释放超过30天，而从Pluronic凝胶中释放的BSA-FITC在3天内停止。总的来说，本研究结果表明，MPEG-PCL二嵌段共聚物溶液是热响应性的，并在生理条件下保持其结构完整性，表明它们适合用作可注射药物载体。
An MPEG-PCL diblock copolymer was synthesized as an in situ gel carrier, and its phase transition behavior in aqueous solutions was examined. For comparison, aqueous solutions of Pluronic F-127, a widely used injectable gel-forming solution, were also studied. Both MPEG-PCL copolymer and Pluronic aqueous solutions were sols at room temperature. As the temperature was increased above room temperature, the diblock copolymer and Pluronic solutions underwent a sol-to-gel phase transition, which manifested as an increase in viscosity indicative of the formation of a gel. All of the copolymer solutions became gels at body temperature, although the gel viscosity increased with the increasing concentration of the MPEG-PCL diblock copolymer in the solution. In in vitro experiments, in which the gels were exposed to PBS, the MPEG-PCL gels maintained their structural integrity for more than 28 days, whereas the Pluronic gel disappeared within 2 days. The same results were observed when the polymer solutions were subcutaneously injected into rats. The MPEG-PCL gels maintained their structural integrity longer than 30 days, while the Pluronic gel could not be observed after 2 days. The ability of the gels as drug carriers was studied by measuring the release of fluorescein isothiocyanate-labeled bovine serum albumin (BSA-FITC) from MPEG-PCL diblock copolymer gels in vitro as well as in vivo. In vitro, BSA release was sustained above 20 days, with a greater release at lower diblock copolymer concentration; by contrast, Pluronic gels exhibited almost complete release of BSA-FITC within 1 day. When the BSA-FITC-loaded diblock copolymer and Pluronic solutions were subcutaneously injected into rats, they immediately transformed into a gel. In vivo, sustained release of BSA-FITC over 30 days was observed from the MPEG-PCL gel, whereas BSA-FITC release from the Pluronic gel ceased within 3 days. Collectively, the present findings show that MPEG-PCL diblock copolymer solutions are thermo-responsive and maintain their structural integrity under physiological conditions, indicating that they are suitable for use as injectable drug carriers.