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Lyophilized silk fibroin hydrogels for the sustained local delivery of therapeutic monoclonal antibodies

Paper ID Volume ID Publish Year Pages File Format Full-Text
8110 577 2011 9 PDF Available
Title
Lyophilized silk fibroin hydrogels for the sustained local delivery of therapeutic monoclonal antibodies
Abstract

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.

Keywords
Silk; Fibroin; Hydrogel; Protein; Antibody; Sustained delivery
First Page Preview
Lyophilized silk fibroin hydrogels for the sustained local delivery of therapeutic monoclonal antibodies
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 10, April 2011, Pages 2642–2650
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering