Accelerating protein release from microparticles for regenerative medicine applications.
Accelerating protein release from microparticles for regenerative medicine applications.
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DOI：
10.1016/j.msec.2013.02.020
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发表时间：
2013-07-01
影响因子：
7.9
通讯作者：
Shakesheff, Kevin M.
中科院分区：
文献类型：
--
作者：
White, Lisa J.;Kirby, Giles T. S.;Cox, Helen C.;Qodratnama, Roozbeh;Qutachi, Omar;Rose, Felicity R. A. J.;Shakesheff, Kevin M.
关键词：
有必要控制生长因子的时空释放动力学，以减少目前高剂量的使用。从PLGA微粒出发，开发了一种既能提供结构支撑又能提供控释动力学的新型给药系统。加入亲水性的PLGA-PEG-PLGA三嵌段共聚物改变了释放动力学，使它们在聚合物降解过程中解耦。使用10%w/w PLGA和50：50 PLGA可在四周内获得准零级释放曲线，而使用30%w/w PLGA和85：15 PLGA可在10天内获得完全和持续释放，使用30%w/w PLGA和50：50 PLGA可获得超过4天的完全和持续释放。这三种制剂有望作为BMP-2、PDGF和血管内皮生长因子等生长因子的载体。还通过混合两种不同配方的微粒来改变释放曲线，提供了另一种以前没有报道的控制释放动力学的途径。该系统提供了可定制的、局部的、可控的、可调节的释放曲线，这将提高重组生长因子的有效性和安全性。►开发了一种提供控释动力学的新给药系统。►包被的亲水性聚乙二醇-聚乙二醇-聚乙二酸乙二醇酯使药物的释放动力学与降解分离。使用10%三嵌段共聚物的►在四周内产生准零级释放。►混合微粒制剂为控制释放提供了另一种途径。►该系统提供可定制、本地化和受控的增长因素交付。
There is a need to control the spatio-temporal release kinetics of growth factors in order to mitigate current usage of high doses. A novel delivery system, capable of providing both structural support and controlled release kinetics, has been developed from PLGA microparticles. The inclusion of a hydrophilic PLGA–PEG–PLGA triblock copolymer altered release kinetics such that they were decoupled from polymer degradation. A quasi zero order release profile over four weeks was produced using 10% w/w PLGA–PEG–PLGA with 50:50 PLGA whereas complete and sustained release was achieved over ten days using 30% w/w PLGA–PEG–PLGA with 85:15 PLGA and over four days using 30% w/w PLGA–PEG–PLGA with 50:50 PLGA. These three formulations are promising candidates for delivery of growth factors such as BMP-2, PDGF and VEGF. Release profiles were also modified by mixing microparticles of two different formulations providing another route, not previously reported, for controlling release kinetics. This system provides customisable, localised and controlled delivery with adjustable release profiles, which will improve the efficacy and safety of recombinant growth factor delivery. ► A new delivery system providing controlled release kinetics has been developed. ► Inclusion of hydrophilic PLGA–PEG–PLGA decoupled release kinetics from degradation. ► Using 10% triblock copolymer produced quasi zero order release over four weeks. ► Mixing microparticle formulations provided another route for controlling release. ► This system provides customisable, localised and controlled delivery of growth factors.
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