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Silylated Precision Particles for Controlled Release of Proteins

机译:甲硅烷基精密颗粒可控制释放蛋白质

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摘要

With the recent advances in the development of novel protein based therapeutics, controlled delivery of these biologics is an important area of research. Herein, we report the synthesis of microparticles from bovine serum albumin (BSA) as a model protein using Particle Replication in Non-wetting Templates (PRINT) with specific size and shape. These particles were functionalized at room temperature using multifunctional chlorosilane that cross-link the particles to render them to slowly-dissolving in aqueous media. Mass spectrometric study of the reaction products of diisopropyldichlorosilane with individual components of the particles revealed that they are capable of reacting and forming cross-links. Energy dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) were also used to confirm the functionalization of the particles. Cross sectional analysis using focused ion beam (FIB) and EDS proved that the functionalization occurs throughout the bulk of the particles and is not just limited to the surface. Circular dichroism data confirmed that the fraction of BSA molecules released from the particles retains its secondary structure thereby indicating that the system can be used for delivering protein based formulations while controlling the dissolution kinetics.
机译:随着基于蛋白质的新型治疗剂的最新发展,这些生物制剂的受控递送是重要的研究领域。在这里,我们报告使用非复制模板(PRINT)中具有特定大小和形状的粒子复制技术,从牛血清白蛋白(BSA)作为模型蛋白合成微粒。使用多功能氯硅烷将这些颗粒在室温下功能化,该多功能氯硅烷使颗粒交联,使其缓慢溶解在水性介质中。对二异丙基二氯硅烷与颗粒中各个组分的反应产物进行的质谱研究表明,它们能够反应并形成交联键。能量色散光谱(EDS)和X射线光电子能谱(XPS)也用于确认颗粒的功能化。使用聚焦离子束(FIB)和EDS进行的横截面分析证明,功能化发生在整个粒子中,而不仅限于表面。圆二色性数据证实了从颗粒释放的BSA分子部分保留了其二级结构,从而表明该系统可用于输送基于蛋白质的制剂,同时控制溶解动力学。

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