Porous Silicon Nanoparticle Hydrogel Formulation for Topical Delivery of Flightless I Neutralizing Antibody and Improved Diabetic Wound Healing

Abstract

Diabetes-related foot ulcers (DRFUs), affecting one-third of individuals with diabetes, are a leading cause of hospitalization. Current treatment options to expedite healing are limited, with the effectiveness of potential therapeutics reduced by the hostile environment inherent to most diabetes-related wounds. Topical delivery vehicles that protect drugs from the protease-enriched wound environment, whilst displaying a slow-release profile, are needed to facilitate wound closure. Biodegradable porous silicon nanoparticles (pSi NPs) in a thermo-sensitive hydrogel formulation are assessed for the delivery of the wound healing therapeutic Flightless I neutralizing antibody (FnAb). FnAb is loaded into pSi NPs at clinically relevant doses and achieves functional antibody release over 14 days. In vitro, pSi NPs effectively protected FnAb from proteolytic degradation by matrix metalloproteinases that are elevated in diabetes-related wounds. FnAb-loaded pSi NPs are formulated into a thermo-responsive hydrogel and delivered topically to type 1 and type 2 diabetic mouse wounds. The hydrogel facilitated FnAb release from pSi NPs until absorbed into the wound bed. A single topical application led to reduced Flightless I, improved wound closure, decreased inflammation, and improved tissue remodeling compared to the delivery of FnAb alone. Together, pSi NP hydrogel is an effective vehicle to deliver therapeutic FnAb to diabetes-related wounds.

Keywords: chronic diabetic wounds; porous silicon nanoparticles; slow release; therapeutic antibody; topical drug delivery.