(182ac) Development of Polymeric Thin Films for Local Delivery of siRNA

Chou, J., MIT
Berger, A. G., Harvard-MIT
Medicinal application of RNA interference (RNAi) holds much potential as a solution to a variety of diseases wherein gene regulation is vital to addressing protein overexpression or dysregulation. Nonetheless, the success of RNAi is contingent on the ability to effectively deliver the therapy to the tissues of interest. Short interfering RNA (siRNA) by itself is readily degraded in the bloodstream and cannot efficiently pass through cell membranes. We present the development of a layer-by-layer (LbL) ultrathin electrostatically assembled polymer coating for localized delivery of siRNA. The LbL thin film was applied to a commercially-available synthetic absorbable surgical suture. Efficacy of the siRNA film coating was optimized by investigation of film assembly conditions including pH, polymer component concentrations, and buffer concentrations. Tuning these conditions, siRNA loading of over 1.5 μg/cm and protein knockdown of over 40% was demonstrated in vitro. Notably, this siRNA coating may be readily applied to alternate medically relevant substrates, such as wound dressings and surgical implants. This presents promising opportunities for localized administration of siRNA to address a variety of issues including wound healing management and modulation of cellular response to implants.