Effect of surface chemistry of porous silicon microparticles on glucagon-like peptide-1 (GLP-1) loading, release and biological activity
Effect of surface chemistry of porous silicon microparticles on glucagon-like peptide-1 (GLP-1) loading, release and biological activity
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DOI：
10.1016/j.ijpharm.2013.06.063
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发表时间：
2013-09-15
影响因子：
5.8
通讯作者：
Jarvinen, Kristiina
中科院分区：
文献类型：
--
作者：
Huotari, Anne;Xu, Wujun;Jarvinen, Kristiina
最近，中孔硅（PSi）微粒已被证明可以延长肽的作用时间，减少频繁注射的需要。胰高血糖素样肽1（Glucagon-like peptide 1，GLP-1）是一种潜在的治疗2型糖尿病的新型药物，本研究旨在评价载于PSi微粒中的GLP-1是否能长期降低血糖水平。GLP-1（pI 5.4）被加载并从带负电荷的热氧化的（TOPSi，pI 1.8）和热扩散（TCPSi，pI 2.6）PSi微粒和命名为TOPSi-NH 2-D的新型带正电荷的胺改性微粒（pI 8.8）和TCPSi-NH 2-D通过将PSi表面电荷从负变为正，GLP-1在PSi微粒上的吸附可以增加3-4倍，表明PSi的正表面电荷促进了带负电荷的肽之间的静电相互作用。所有负载GLP-1的PSi微粒在单次s.c.注射后，T0 PSi-NH 2-D和TCPSi-NH 2-D的作用没有延长，但令人惊讶的是，与T0 PSi、TCPSi或GLP-1溶液相比，T0 PSi-NH 2-D和TCPSi-NH 2-D不能延长作用。然而，TOPSi-NH 2-D和TCPSi-NH 2-D微粒能够携带活性GLP-1的改善的有效载荷，从而鼓励继续进一步尝试实现持续释放。(c)2013爱思唯尔有限公司版权所有。
Recently, mesoporous silicon (PSi) microparticles have been shown to extend the duration of action of peptides, reducing the need for frequent injections. Glucagon-like peptide 1 (GLP-1) is a potential novel treatment for type 2 diabetes.The aim of this study was to evaluate whether GLP-1 loading into PSi microparticles reduce blood glucose levels over an extended period. GLP-1 (pI 5.4) was loaded and released from the negatively charged thermally oxidized (TOPSi, pI 1.8) and thermally carbonized (TCPSi, pI 2.6) PSi microparticles and from the novel positively charged amine modified microparticles, designated as TOPSi-NH2-D (pI 8.8) and TCPSi-NH2-D (pI 8.8), respectively.The adsorption of GLP-1 onto the PSi microparticles could be increased 3-4-fold by changing the PSi surface charge from negative to positive, indicating that the positive surface charge of PSi promoted an electrostatic interaction between the negatively charged peptide. All the GLP-1 loaded PSi microparticles lowered the blood glucose levels after a single s.c. injection but surprisingly, TOPSi-NH2-D and TCPSi-NH2-D were not able to prolong the effect when compared to TOPSi, TCPSi or GLP-1 solution. However, TOPSi-NH2-D and TCPSi-NH2-D microparticles were able to carry improved payloads of active GLP-1 encouraging continuing further attempts to achieve sustained release. (c) 2013 Elsevier B.V. All rights reserved.