Molecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide.
Molecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide.
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DOI：
10.1038/s41598-018-24897-9
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发表时间：
2018-05-21
影响因子：
4.6
通讯作者：
Bidwell GL 3rd
中科院分区：
文献类型：
--
作者：
Kuna M;Mahdi F;Chade AR;Bidwell GL 3rd
弹性蛋白样多肽（Elastin-like polypeptides，ELP）是由5个氨基酸基序的重复组成的工程蛋白质，并且它们的组成容易被修饰以调节它们的物理性质并附着治疗剂。由于ELP序列的重复性质，聚合物大小特别易于操纵。ELP融合蛋白正被积极开发作为许多疾病应用的治疗剂，并且ELP大小和形状如何影响其药代动力学和生物分布是ELP药物递送的一般领域的关键问题。为了解决这个问题，我们产生了一个大小从25 kDa到110 kDa的ELP文库。终末血浆半衰期与聚合物尺寸成正比，器官生物分布也与尺寸相关。肾脏中ELP的积累水平最高，其次是肝脏。在肾脏内，大多数ELP被发现在近端小管，但肾内定位转移，从纯粹的皮质混合物的皮质和髓质ELP的大小增加。
Elastin-like polypeptides (ELP) are engineered proteins that consist of repetitions of a five amino acid motif, and their composition is easily modified to adjust their physical properties and attach therapeutics. Because of the repetitive nature of the ELP sequence, polymer size is particularly amenable to manipulation. ELP fusion proteins are being actively developed as therapeutics for many disease applications, and how the ELP size and shape affects its pharmacokinetics and biodistribution is a critical question for the general field of ELP drug delivery. To address this, we generated a library of ELPs ranging in size from 25 kDa to 110 kDa. Terminal plasma half-life was directly proportional to polymer size, and organ biodistribution was also size dependent. The kidneys accumulated the highest levels of ELP of all sizes, followed by the liver. Within the kidney, most ELP was found in the proximal tubule, but intra-renal localization shifted from exclusively cortical to a mixture of cortical and medullary as ELP size increased.
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影响因子：
3.7
作者：
Bidwell GL 3rd;Perkins E;Hughes J;Khan M;James JR;Raucher D
通讯作者：
Raucher D
影响因子：
10.3
作者：
Dreher, MR;Liu, WG;Chilkoti, A
通讯作者：
Chilkoti, A
DOI：
10.1152/ajprenal.00143.2016
发表时间：
2017-01-01
影响因子：
4.2
作者：
Bidwell, Gene L., III;Mahdi, Fakhri;Chade, Alejandro R.
通讯作者：
Chade, Alejandro R.
DOI：
10.1016/j.jconrel.2013.07.021
发表时间：
2013-11-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Amiram M;Luginbuhl KM;Li X;Feinglos MN;Chilkoti A
通讯作者：
Chilkoti A
影响因子：
6.2
作者：
McDaniel, Jonathan R.;MacKay, J. Andrew;Quiroz, Felipe Garcia;Chilkoti, Ashutosh
通讯作者：
Chilkoti, Ashutosh