Ultrasonication-Induced Preparation of High-Mechanical-Strength Microneedles Using Stable Silk Fibroin

Silk fibroin (SF) is an ideal material for microneedle (MN) preparation. However, long extraction and short storage durations limit its application. Furthermore, MNs prepared from SF alone are easy to break during skin insertion. In this study, a regenerated SF solution was autoclaved and freeze-dried to produce a stable and water-soluble SF sponge. The freeze-dried SF (FD-SF) solution was ultrasonically treated before being used in the fabrication of MNs. The ultrasonically modified SFMNs (US-SFMNs) were evaluated in comparison to FD-SFMNs made from FD-SF and conventional SFMNs made from regenerated SF. The results indicated that the FD-SF could be completely dissolved in water and remained stable even after 8 months of storage. FTIR and XRD analyses showed that SF in US-SFMNs had increased β-sheet content and crystallization compared to FD-SFMNs, by 7.3% and 8.1%, respectively. The US-SFMNs had higher mechanical strength than conventional SFMNs and FD-SFMNs, with a fracture force of 1.55 N per needle and a rat skin insertion depth of 370 μm. The US-SFMNs also demonstrated enhanced transdermal drug delivery and enzymatic degradation in vitro. In conclusion, the autoclaving and freeze drying of SF, as well as ultrasonication-induced MN preparation, provide promising SF-based microneedles for transdermal drug delivery.