Rodionov Ilya A, Abdullah Nadia, Kaplan David L
Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, Massachusetts 02155, United States.
Adv Eng Mater. 2019 Jul;21(7). doi: 10.1002/adem.201801242. Epub 2019 Apr 18.
A facile method for the preparation of large, microporous, drug-loaded particles is presented. High shear bollus injections of silk with cross-linker and drug colloids into super-cooled hexane were utilized to trigger phase separation of silk droplets, followed by immediate freezing at -60°C. A subsequent -20°C freeze-thaw of the frozen droplets resulted in self-assembly (crystallization) of the silk. The silk particles developed an internal interconnected microporous morphology with 0.1-10 µm in diameter pores. The silk particles ranged in diameter from 100 to 1,300 µm, with particle mean diameter and polydispersity controlled by the starting concentration of the cross-linking agent and silk, the rheology of the reaction mixture, and the injection pressure (80 - 300kPa). Cryogranulation provided a one-step process to produce microporous meso-scale silk particles with encapsulated drugs, such as doxorubicin chloride (DoxR), tobramycin sulfate (TS), kanamycin sulfate (KS) or gentamicin sulfate (GS). Almost 100% drug encapsulation efficiency was achieved in the process, and subsequent release profiles depended on the starting concentration of both the drug, silk, and pH of the elution medium. Kirby-Bauer tests and bioluminescent imaging confirmed the retention of anti-bacterial potency of the antibiotics pre-encapsulated in the cryo-particles, and macroparticles cytocompatibility towards human fibroblast and kidney cells.
本文介绍了一种制备大尺寸、微孔、载药颗粒的简便方法。利用高剪切柱塞注射将含交联剂和药物胶体的丝溶液注入过冷己烷中，引发丝滴的相分离，随后立即在-60°C冷冻。对冷冻后的液滴进行后续-20°C的冻融处理，使丝发生自组装（结晶）。所得丝颗粒形成内部相互连通的微孔形态，孔径为0.1 - 10 µm。丝颗粒直径范围为100至1300 µm，颗粒平均直径和多分散性可通过交联剂和丝的起始浓度、反应混合物的流变学以及注射压力（80 - 300kPa）进行控制。冷冻造粒提供了一种一步法来制备包裹药物（如盐酸多柔比星（DoxR）、硫酸妥布霉素（TS）、硫酸卡那霉素（KS）或硫酸庆大霉素（GS））的微孔中尺度丝颗粒。在此过程中实现了几乎100%的药物包封效率，随后的释放曲线取决于药物、丝的起始浓度以及洗脱介质的pH值。纸片扩散法测试和生物发光成像证实了预包裹在冷冻颗粒中的抗生素的抗菌效力得以保留，以及大颗粒对人成纤维细胞和肾细胞的细胞相容性。
