Background: Non-healing foot ulcers are a major health concern for diabetics. Treatment options remain severely limited, especially as topically administered drugs are often compromised by the hostile environment inherent to most chronic wounds. Thus, there is an urgent need to develop innovative drug carriers/vehicles to deliver promising therapeutic agents for improved healing of diabetic wounds. We have developed porous silicon (pSi) nanomaterials for applications in drug delivery. pSi is a biodegradable, high surface area material that has already demonstrated its safety and potential in drug delivery applications. Therapeutic anti-Flightless I antibodies (FnAb) improve wound healing and are an ideal candidate for delivery to diabetic wounds by pSi. The use of pSi NPs to deliver FnAb to diabetic wounds was therefore hypothesized to improved diabetic wound healing.
Methods: pSi was optimized for the delivery of FnAb to wounds, including (1) determining the stability/functionality of loaded antibodies, (2) ability to protect antibodies from protease-mediated degradation, (3) tuning the rate of release based on pH and/or temperature, and (4) loading with a high concentration of payload using a simple method that is upscale-able. Next, the efficacy of FnAb pSi to improve wound healing was assessed in a diabetic mouse wound model, examining different delivery strategies.
Results: FnAb loading regimens exceeded 250 μg antibody per mg of pSi. FnAb released from pSi in vitro was confirmed to retain structural integrity and increased keratinocyte proliferation and migration in vitro. pSi NPs protected FnAb from protease digestion for up to 7 d post-treatment. Using a streptozotocin-induced model of diabetic wounding, FnAb delivered by pSi improved healing compared to vehicle-treated wounds. Saliently, FnAb pSi was more effective at improving wound repair than when FnAb was delivered alone.
Conclusion: pSi NPs may therefore enable new therapeutic approaches for the treatment of diabetic ulcers.