Microneedles (MNs) have attracted great interest as a drug delivery alternative to subcutaneous injections for treating diabetes mellitus. We report MNs prepared from polylysine-modified cationized silk fibroin (SF) for responsive transdermal insulin delivery. Scanning electron microscopy analysis of MNs’ appearance and morphology revealed that the MNs were well arranged and formed an array with 0.5 mm pitch, and the length of single MNs is approximately 430 μm. The average breaking force of an MN is above 1.25 N, which guarantees that it can pierce the skin quickly and reach the dermis. Cationized SF MNs are pH-responsive. MNs dissolution rate increases as pH decreases and the rate of insulin release are accelerated. The swelling rate reached 223% at pH = 4, while only 172% at pH = 9. After adding glucose oxidase, cationized SF MNs are glucose-responsive. As the glucose concentration increases, the pH inside the MNs decreases, the MNs’ pore size increases, and the insulin release rate accelerates. In vivo experiments demonstrated that in normal Sprague Dawley (SD) rats, the amount of insulin released within the SF MNs was significantly smaller than that in diabetic rats. Before feeding, the blood glucose (BG) of diabetic rats in the injection group decreased rapidly to 6.9 mmol/L, and the diabetic rats in the patch group gradually reduced to 11.7 mmol/L. After feeding, the BG of diabetic rats in the injection group increased rapidly to 33.1 mmol/L and decreased slowly, while the diabetic rats in the patch group increased first to 21.7 mmol/L and then decreased to 15.3 mmol/L at 6 h. This demonstrated that the insulin inside the microneedle was released as the blood glucose concentration increased. Cationized SF MNs are expected to replace subcutaneous injections of insulin as a new modality for diabetes treatment.

Microneedles are a patient-friendly technique for delivering drugs to the site of action in place of traditional oral and injectable administration. Silk fibroin represents an interesting polymeric biomaterial because of its mechanical properties, thermal stability, biocompatibility and possibility of control via genetic engineering. This review focuses on the critical research progress of silk fibroin microneedles since their inception, analyzes in detail the structure and properties of silk fibroin, the types of silk fibroin microneedles, drug delivery applications and clinical trials, and summarizes the future development trend in this field. It also proposes the future research direction of silk fibroin microneedles, including increasing drug loading doses and enriching drug loading types as well as exploring silk fibroin microneedles with stimulation-responsive drug release functions. The safety and effectiveness of silk fibroin microneedles should be further verified in clinical trials at different stages.

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