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具有控制表面结构的蛋白质纳米基质颗粒的形成及其在呼吸给药中的应用。

Formation of protein nano-matrix particles with controlled surface architecture for respiratory drug delivery.

机构信息

Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Building A15, Camperdown, NSW, 2006, Australia.

出版信息

Pharm Res. 2011 Apr;28(4):788-96. doi: 10.1007/s11095-010-0332-2. Epub 2010 Dec 7.

DOI:10.1007/s11095-010-0332-2
PMID:21136142
Abstract

PURPOSE

To produce and examine the aerosol performance of protein nano-matrix particles with different surface roughness.

METHODS

Aqueous lysozyme solutions were poured into isopropanol during high-shear mixing to produce nanoparticles by precipitation. The size of the nanoparticles was varied by adjusting the precipitation conditions. The resultant suspensions were spray-dried to obtain micron-sized aggregates (nano-matrices). Smooth particles were made by spray-drying a lysozyme solution. The aggregate size distribution, surface roughness, and cohesion were evaluated. The aerosol performance was assessed by dispersing 10 mg of powder from a Rotahaler(®) at 60 L/min or an Aerolizer® at 100 L/min into a Next Generation Impactor, followed by chemical assay (n=3).

RESULTS

The median volume diameter and span of the nano-matrix particles were 1.0-1.2 μm and 1.5-1.6, respectively, which were comparable to those of the smooth particles. Surface roughness increased with the size of the primary nanoparticles. The nano-matrix particles were significantly less cohesive than the smooth particles. The fine particle fraction increased linearly with increasing surface roughness and decreasing cohesion.

CONCLUSIONS

Nano-matrix particles with controlled surface architecture were successfully produced by spray-drying nanosuspensions. Aerosol performance was enhanced with increasing surface roughness due to the reduction in cohesion forces.

摘要

目的

制备并考察不同表面粗糙度的蛋白质纳米基质颗粒的气溶胶性能。

方法

在高剪切混合过程中将溶菌酶水溶液倒入异丙醇中,通过沉淀生成纳米颗粒。通过调整沉淀条件来改变纳米颗粒的粒径。所得悬浮液经喷雾干燥制成微米级聚集体(纳米基质)。通过喷雾干燥溶菌酶溶液来制备光滑的颗粒。评估了颗粒的粒径分布、表面粗糙度和内聚性。通过以 60 L/min 从 Rotahaler(®)或 100 L/min 从 Aerolizer(®)分散 10 mg 粉末,将其分散到下一代撞击器中,然后进行化学分析(n=3)来评估气溶胶性能。

结果

纳米基质颗粒的中值体积直径和跨度分别为 1.0-1.2 μm 和 1.5-1.6,与光滑颗粒相当。表面粗糙度随初级纳米颗粒的粒径增大而增加。纳米基质颗粒的内聚性明显低于光滑颗粒。随着表面粗糙度的增加和内聚性的降低,细颗粒分数呈线性增加。

结论

通过喷雾干燥纳米混悬液成功制备了具有可控表面结构的纳米基质颗粒。由于内聚力的降低,气溶胶性能随表面粗糙度的增加而提高。

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