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孔径是从电化学合成的介孔硅微粒中实现蛋白质持续释放的关键参数。

Pore size is a critical parameter for obtaining sustained protein release from electrochemically synthesized mesoporous silicon microparticles.

作者信息

Pastor Ester L, Reguera-Nuñez Elaine, Matveeva Eugenia, Garcia-Fuentes Marcos

机构信息

EM Silicon Nanotechnologies, S.L. , Valencia , Spain.

Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela , Santiago de Compostela , Spain.

出版信息

PeerJ. 2015 Oct 6;3:e1277. doi: 10.7717/peerj.1277. eCollection 2015.

Abstract

Mesoporous silicon has become a material of high interest for drug delivery due to its outstanding internal surface area and inherent biodegradability. We have previously reported the preparation of mesoporous silicon microparticles (MS-MPs) synthesized by an advantageous electrochemical method, and showed that due to their inner structure they can adsorb proteins in amounts exceeding the mass of the carrier itself. Protein release from these MS-MPs showed low burst effect and fast delivery kinetics with complete release in a few hours. In this work, we explored if tailoring the size of the inner pores of the particles would retard the protein release process. To address this hypothesis, three new MS-MPs prototypes were prepared by electrochemical synthesis, and the resulting carriers were characterized for morphology, particle size, and pore structure. All MS-MP prototypes had 90 µm mean particle size, but depending on the current density applied for synthesis, pore size changed between 5 and 13 nm. The model protein α-chymotrypsinogen was loaded into MS-MPs by adsorption and solvent evaporation. In the subsequent release experiments, no burst release of the protein was detected for any prototype. However, prototypes with larger pores (>10 nm) reached 100% release in 24-48 h, whereas prototypes with small mesopores (<6 nm) still retained most of their cargo after 96 h. MS-MPs with ∼6 nm pores were loaded with the osteogenic factor BMP7, and sustained release of this protein for up to two weeks was achieved. In conclusion, our results confirm that tailoring pore size can modify protein release from MS-MPs, and that prototypes with potential therapeutic utility for regional delivery of osteogenic factors can be prepared by convenient techniques.

摘要

由于其出色的内表面积和固有的生物可降解性,介孔硅已成为药物递送领域备受关注的材料。我们之前报道过通过一种有利的电化学方法合成介孔硅微粒(MS-MPs),并表明由于其内部结构,它们能够吸附超过载体本身质量的蛋白质。这些MS-MPs的蛋白质释放显示出低突释效应和快速的递送动力学,在几小时内即可完全释放。在这项工作中,我们探究了调整颗粒内部孔隙的大小是否会延缓蛋白质释放过程。为了验证这一假设,通过电化学合成制备了三种新的MS-MPs原型,并对所得载体的形态、粒径和孔结构进行了表征。所有MS-MP原型的平均粒径均为90 µm,但根据合成时施加的电流密度不同,孔径在5至13 nm之间变化。通过吸附和溶剂蒸发将模型蛋白α-胰凝乳蛋白酶原加载到MS-MPs中。在随后的释放实验中,未检测到任何原型有蛋白质的突释现象。然而,孔径较大(>10 nm)的原型在24 - 48小时内达到100%释放,而具有小介孔(<6 nm)的原型在96小时后仍保留了大部分所载物质。将孔径约为6 nm的MS-MPs加载成骨因子BMP7,并实现了该蛋白质长达两周的持续释放。总之,我们的结果证实调整孔径可以改变MS-MPs中蛋白质的释放,并且可以通过简便技术制备出对成骨因子区域递送具有潜在治疗效用的原型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82be/4636406/16f9228ad485/peerj-03-1277-g001.jpg

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