Chitosan/siRNA nanoparticles for biological refinement of medical implants

RNA interference can be employed to develop a new class of drugs that interfere with disease genes, thereby inhibiting the synthesis of designated target proteins. To allow therapeutic application of siRNA, we utilize the biomaterial chitosan for stabilization, promotion of cellular uptake, and immobilization of siRNA on implant surfaces. The goal is (1) to foster regeneration of the nervous system and (2) to inhibit fibrotic implant encapsulation.Gel retardation assays indicate that chitosan/siRNA particles possess high stability. Particle size and zeta potential were analyzed by photon correlation spectroscopy whereby both parameters increased with higher chitosan ratio. In cell culture, siRNA nanoparticles displayed low cytotoxicity and did not induce an inflammatory response, as shown by the Oas-1 level. siRNA nanoparticle uptake was efficient and resulted in silencing of target mRNA and the corresponding proteins which play decisive roles in neuronal regeneration and fibrotic overgrowth. Moreover, chitosan/siRNA nanoparticles could be successfully immobilized onto polymer-based nerve guides.

Chitosan/siRNA nanoparticles are an innovative drug delivery tool which allow biological functionalization of medical implants. Our results especially highlight the potential application for (1) enhancement of neuronal regeneration and (2) inhibition of fibrotic encapsulation of medical implants. Our aim for the future is to use siRNA nanoparticles as a cross-sectional technology and to bind siRNA as a bioactive molecule to a variety of medical implants.

Partly supported by BW-Stiftung (P-LS-Biomat/26), EuroNanoMed (13N11036) and BMBF.