Implantable drug delivery systems with a bioinspired zwitterionic nanocoating resist foreign body reaction-induced obstruction and enable sustained delivery.

Implantable drug delivery systems (IDDS) hold great promise for sustained therapeutic administration, particularly for deep tissues like the inner ear. However, the obstruction of delivery systems induced by foreign body reactions (FBRs) remains a significant challenge to long-term implantation. Here, we developed a bio-inspired zwitterionic nanocoating (PDA-PSB) for IDDS. Experimental results showed that the PDA-PSB coating significantly improved the hydrophilicity, reduced protein and cell adhesion, and effectively suppressed inflammatory responses. To evaluate the long-term performance, we implanted PDA-PSB-coated microcatheters subcutaneously and in the tympanic bullae of rats for six months. Dynamic observations revealed that, in the uncoated group, fibrotic tissues resulting from the FBRs gradually infiltrated the lumen of the microcatheter, ultimately causing complete occlusion. In contrast, the PDA-PSB-coated microcatheters significantly reduced the fibrosis and prevented obstruction. Pressure measurements further demonstrated that the PDA-PSB-coated microcatheters maintained low drug delivery pressure after long-term implantation, ensuring sustained patency and continuous drug delivery. Mechanistic studies revealed that the PDA-PSB coating inhibited early macrophage M1 polarization and prevented macrophage transition into myofibroblasts (MMT), thereby reducing collagen deposition. This study provides a novel solution for improving the performance of IDDS and highlights its considerable potential for long-term application.