Amyloid as a depot for the formulation of long-acting drugs.
Amyloid as a depot for the formulation of long-acting drugs.
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DOI：
10.1371/journal.pbio.0060017
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发表时间：
2008-02
期刊：
影响因子：
9.8
通讯作者：
Riek R
中科院分区：
文献类型：
--
作者：
Maji SK;Schubert D;Rivier C;Lee S;Rivier JE;Riek R
淀粉样蛋白是一种高度组织化的蛋白质聚集体，与阿尔茨海默病等神经退行性疾病和皮肤色素沉着等良性功能有关。淀粉样蛋白通过招募相应的可溶性蛋白质/多肽，以一种依赖于成核的方式自我聚合，并在恶劣的物理、化学和生化条件下保持稳定。这些非凡的性质使淀粉样蛋白在纳米技术中的应用具有吸引力。在这里，我们建议在长效药物的配方中使用淀粉样蛋白。我们的基本原理是，淀粉样蛋白具有长效药物所需的特性，因为它们是保证活性多肽药物从淀粉样蛋白末端控制释放的稳定仓库。这一概念通过一系列促性腺激素释放激素(GnRH)的短效和长效类似物进行了测试，结果表明，其淀粉样蛋白可以作为生物活性多肽持续释放的来源。淀粉样蛋白是一种高度组织化的蛋白质聚集体，与阿尔茨海默病等神经退行性疾病和皮肤色素沉着等良性功能有关。淀粉样蛋白通过招募其可溶蛋白来自我聚合，并在恶劣的物理、化学和生化条件下保持稳定。这些非凡的性质使淀粉样蛋白在纳米技术中的应用具有吸引力。在这里，我们建议在长效药物的配方中使用淀粉样蛋白，这种药物在几天和几周的较长时间内都有效。长效药物的设计目的是提高患者的舒适度、便利性、剂量准确性，并保证患者对口服生物利用度较低的药物的依从性。我们的基本原理是，淀粉样蛋白具有长效药物所需的特性，因为它们是保证活性多肽药物从淀粉样蛋白末端控制释放的稳定仓库。这一概念通过一系列促性腺激素释放激素的短效和长效类似物进行了测试，结果表明，其淀粉样蛋白可以作为生物活性多肽持续释放的来源。淀粉样蛋白具有长效药物所需的特性，因为它们是保证活性多肽药物从淀粉样蛋白末端受控释放的稳定储存库。
Amyloids are highly organized protein aggregates that are associated with both neurodegenerative diseases such as Alzheimer disease and benign functions like skin pigmentation. Amyloids self-polymerize in a nucleation-dependent manner by recruiting their soluble protein/peptide counterpart and are stable against harsh physical, chemical, and biochemical conditions. These extraordinary properties make amyloids attractive for applications in nanotechnology. Here, we suggest the use of amyloids in the formulation of long-acting drugs. It is our rationale that amyloids have the properties required of a long-acting drug because they are stable depots that guarantee a controlled release of the active peptide drug from the amyloid termini. This concept is tested with a family of short- and long-acting analogs of gonadotropin-releasing hormone (GnRH), and it is shown that amyloids thereof can act as a source for the sustained release of biologically active peptides. Amyloids are highly organized protein aggregates that are associated with both neurodegenerative diseases such as Alzheimer disease and benign functions such as skin pigmentation. Amyloids self-polymerize by recruiting their soluble protein counterpart and remain stable against harsh physical, chemical, and biochemical conditions. These extraordinary properties make amyloids attractive for applications in nanotechnology. Here, we suggest the use of amyloids in the formulation of long-acting drugs, which are active over extended periods of days and weeks. Long-acting drugs have been designed to increase patient comfort, convenience, dosage accuracy, and assurance of patient compliance for drugs that have a low oral bioavailability. It is our rationale that amyloids have the properties required of a long-acting drug because they are stable depots that guarantee a controlled release of the active peptide drug from the amyloid termini. This concept is tested with a family of short- and long-acting analogs of gonadotropin-releasing hormone, and it is shown that amyloids thereof can act as a source for the sustained release of biologically active peptides. Amyloids have the properties required of a long-acting drug because they are stable depots that guarantee a controlled release of the active peptide drug from the amyloid termini.
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影响因子：
8.2
作者：
DISCHE, FE;WERNSTEDT, C;WATKINS, PJ
通讯作者：
WATKINS, PJ
影响因子：
46.9
作者：
Brader, ML;Sukumar, M;Myers, SR
通讯作者：
Myers, SR
DOI：
10.1124/jpet.301.1.95
发表时间：
2002-04-01
影响因子：
3.5
作者：
Broqua, P;Riviere, PJM;Junien, JL
通讯作者：
Junien, JL
DOI：
10.1073/pnas.96.7.3590
发表时间：
1999-03-30
影响因子：
11.1
作者：
Chiti, F;Webster, P;Dobson, CM
通讯作者：
Dobson, CM
DOI：
10.1073/pnas.97.12.6728
发表时间：
2000-06-06
影响因子：
11.1
作者：
Holmes, TC;de Lacalle, S;Zhang, SG
通讯作者：
Zhang, SG