Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
Biomaterials. 2010 Feb;31(6):1025-35. doi: 10.1016/j.biomaterials.2009.11.002. Epub 2009 Nov 27.
Silk fibroin protein-based micro- and nanospheres provide new options for drug delivery due to their biocompatibility, biodegradability and their tunable drug loading and release properties. In the present study, we report a new aqueous-based preparation method for silk spheres with controllable sphere size and shape. The preparation was based on phase separation between silk fibroin and polyvinyl alcohol (PVA) at a weight ratio of 1/1 and 1/4. Water-insoluble silk spheres were easily obtained from the blend in a three step process: (1) air-drying the blend solution into a film, (2) film dissolution in water and (3) removal of residual PVA by subsequent centrifugation. In both cases, the spheres had approximately 30% beta-sheet content and less than 5% residual PVA. Spindle-shaped silk particles, as opposed to the spherical particles formed above, were obtained by stretching the blend films before dissolving in water. Compared to the 1/1 ratio sample, the silk spheres prepared from the 1/4 ratio sample showed a more homogeneous size distribution ranging from 300 nm up to 20 microm. Further studies showed that sphere size and polydispersity could be controlled either by changing the concentration of silk and PVA or by applying ultrasonication on the blend solution. Drug loading was achieved by mixing model drugs in the original silk solution. The distribution and loading efficiency of the drug molecules in silk spheres depended on their hydrophobicity and charge, resulting in different drug release profiles. The entire fabrication procedure could be completed within one day. The only chemical used in the preparation except water was PVA, an FDA-approved ingredient in drug formulations. Silk micro- and nanospheres reported have potential as drug delivery carriers in a variety of biomedical applications.
丝素蛋白基微球和纳米球由于其生物相容性、可生物降解性以及可调节的药物负载和释放性能，为药物传递提供了新的选择。在本研究中，我们报告了一种新的基于丝素蛋白和聚乙烯醇（PVA）的水基制备方法，可控制球的大小和形状。该制备方法基于丝素蛋白和 PVA 的重量比为 1/1 和 1/4 时的相分离。在三步法中，很容易从共混物中获得不溶于水的丝球：（1）将共混溶液空气干燥成膜，（2）将膜溶解在水中，（3）通过随后的离心去除残留的 PVA。在这两种情况下，球都有约 30%的β-折叠含量和小于 5%的残留 PVA。与上述形成的球形颗粒相反，通过在溶解于水之前拉伸共混物薄膜，得到了纺锤形的丝颗粒。与 1/1 比例的样品相比，由 1/4 比例的样品制备的丝球显示出更均匀的尺寸分布，范围从 300nm 到 20μm。进一步的研究表明，通过改变丝和 PVA 的浓度或对共混溶液施加超声处理，可以控制球的大小和多分散性。通过将模型药物混合到原始丝溶液中来实现药物负载。药物分子在丝球中的分布和负载效率取决于其疏水性和电荷，从而导致不同的药物释放曲线。整个制造过程可以在一天内完成。除水以外，制备过程中仅使用的化学物质是 PVA，它是药物制剂中 FDA 批准的成分。所报道的丝微球和纳米球具有作为各种生物医学应用中的药物输送载体的潜力。
