BioFormulations Development, Genzyme Corporation, 1 Mountain Road, P.O. Box 9322, Framingham, MA 01701-9322, USA.
Biomaterials. 2011 Apr;32(10):2642-50. doi: 10.1016/j.biomaterials.2010.12.023. Epub 2011 Jan 8.
The development of sustained delivery systems compatible with protein therapeutics continues to be a significant unmet need. A lyophilized silk fibroin hydrogel matrix (lyogel) for the sustained release of pharmaceutically relevant monoclonal antibodies is described. Sonication of silk fibroin prior to antibody incorporation avoids exposing the antibody to the sol-gel transition inducing shear stress. Fourier Transform Infrared (FTIR) analysis showed no change in silk structural composition between hydrogel and lyogel or with increasing silk fibroin concentration. Antibody release from hydrogels occurred rapidly over 10 days regardless of silk concentration. Upon lyophilization, sustained antibody release was observed over 38 days from lyogels containing 6.2% (w/w) silk fibroin and above. In 3.2% (w/w) silk lyogels, antibody release was comparable to hydrogels. Swelling properties of lyogels followed a similar threshold behavior. Lyogels at 3.2% (w/w) silk recovered approximately 90% of their fluid mass upon rehydration, while approximately 50% fluid recovery was observed at 6.2% (w/w) silk and above. Antibody release was primarily governed by hydrophobic/hydrophilic silk-antibody interactions and secondarily altered by the hydration resistance of the lyogel. Hydration resistance was controlled by altering β-sheet (crystalline) density of the matrix. The antibody released from lyogels maintained biological activity. Silk lyogels offer an advantage as a delivery matrix over other hydrogel materials for the slow release of the loaded protein, making lyogels suitable for long-term sustained release applications.
开发与蛋白质治疗药物相容的持续传递系统仍然是一个重大的未满足需求。本文描述了一种用于持续释放药物相关单克隆抗体的冻干丝素水凝胶基质（冻干胶）。在加入抗体之前对丝素进行超声处理可避免抗体暴露于诱导溶胶-凝胶转变的剪切应力下。傅里叶变换红外（FTIR）分析表明，水凝胶和冻干胶之间或随着丝素浓度的增加，丝素结构组成没有变化。无论丝素浓度如何，水凝胶中的抗体在 10 天内迅速释放。冻干后，含有 6.2%（w/w）丝素及以上的冻干胶可观察到 38 天以上的持续抗体释放。在 3.2%（w/w）丝素的冻干胶中，抗体释放与水凝胶相当。冻干胶的溶胀性能遵循相似的阈值行为。在 3.2%（w/w）丝素的冻干胶中，重新水合后约可恢复 90%的流体质量，而在 6.2%（w/w）丝素及以上时，约可恢复 50%的流体质量。抗体释放主要受疏水性/亲水性丝素-抗体相互作用控制，其次受冻干胶的水合阻力影响。通过改变基质中β-折叠（结晶）密度来控制水合阻力。从冻干胶中释放的抗体保持生物活性。与其他水凝胶材料相比，丝素冻干胶作为递送基质具有优势，可用于负载蛋白的缓慢释放，使冻干胶适合于长期持续释放应用。
