Impact of different PEGylation patterns on the long-term bio-stability of colloidal mesoporous silica nanoparticles

Impact of different PEGylation patterns on the long-term bio-stability of colloidal mesoporous silica nanoparticles
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DOI:
10.1039/c0jm01390k
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发表时间:
2010-01-01
影响因子:
--
通讯作者:
Bein, Thomas
Bein, Thomas
中科院分区:
其他
文献类型:
--
作者:
Cauda, Valentina;Argyo, Christian;Bein, Thomas

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无机-有机核壳介孔二氧化硅纳米颗粒作为药物载体具有很高的潜力。它们可以将介孔核心中高负载水平的客体分子与有机外壳结合起来,显示出刺激响应的控制释放能力、胶体悬浮液的高度稳定性和生物相容性。我们描述了胶体核-壳介孔二氧化硅(CMS)纳米颗粒与亲水性聚合物外壳(聚乙二醇,PEG)的外部涂层。通过延迟共缩合的方法,在纳米颗粒生长过程中的一定时间段后,将不同的聚乙二醇硅烷前驱体加入到CMS合成溶液中。具体地说,得到了三种不同类型的线性聚乙二醇化CMS纳米粒子,具有两种不同的聚乙二醇链长度(I)M-w 550,(Ii)M-w 5000,以及(Iii)后两者的混合物(75mol%的M(W)550和25mol%的M(W)5000)。样品通过不同的技术进行了表征,表现出高的比表面积和孔体积,二氧化硅纳米颗粒有效地覆盖了聚乙二醇层(例如,12%w/w的线性聚乙二醇5000),以及相对于未功能化的CMS纳米颗粒,改进了单分散悬浮液在水和生物介质中的作用。研究了聚乙二醇包覆的CMS纳米颗粒在37℃的模拟体液(SBF)中长达1个月的行为,目的是对这些有机-无机杂化纳米颗粒的稳定性和生物降解性有新的了解。根据覆盖物的密度和聚合物的链长,聚乙二醇壳显著降低了SBF中二氧化硅的降解速度。本研究扩展了聚乙二醇化的方法来开发生物相容的杂化纳米载体,用于药物输送应用。
Inorganic-organic core-shell mesoporous silica nanoparticles have high potential as drug delivery vehicles. They can combine high loading levels of guest molecules in the mesoporous core with an organic shell showing stimuli-responsive controlled release capabilities, high stabilization in colloidal suspension, and biocompatibility. We describe colloidal core-shell mesoporous silica (CMS) nanoparticles with an external coating of a hydrophilic polymer shell (poly(ethylene glycol), PEG). By means of a delayed co-condensation approach, different PEG-silane precursors were added to the CMS synthesis solution after certain time periods during the nanoparticle growth. Specifically, three different types of linear PEGylated CMS nanoparticles were obtained, having two different PEG-chain lengths with (i) M-w 550, (ii) M-w 5000, and (iii) a mixture of the latter two (75 mol% of M(w)550 and 25 mol% of M(w)5000). Samples were characterized by different techniques, showing high surface area and pore volume, an effective coating of the silica nanoparticles with the PEG layer (e. g., 12% w/w of linear PEG5000), and improved monodisperse suspension in water and biological media with respect to the unfunctionalized CMS nanoparticles. The behavior of PEG-coated CMS nanoparticles was investigated in simulated body fluid (SBF) for up to 1 month at 37 degrees C, with the aim of gaining new insights regarding the stability and bio-degradability of these organic-inorganic hybrid nanoparticles. Depending on the density of the coverage and the chain length of the polymer, the PEG-shell significantly reduces the rate of degradation of silica in SBF. The present study extends the PEGylation approach to develop biocompatible hybrid nanocarriers for drug delivery applications.