Biomimetic Targeted Drug Delivery for Liver Failure in Abdominal Sepsis: Focus on Autologous Erythrocyte Ghosts.

Sepsis-induced liver failure remains a serious and often under-recognized complication of abdominal sepsis. Clinical reports suggest that liver dysfunction develops in a substantial proportion of these patients, and once failure ensues, mortality rises sharply. Despite progress in antimicrobial therapy and critical care support, there is still no therapy that directly halts or reliably reverses septic liver injury. Systemic drug administration frequently underperforms in this setting. Hepatic drug accumulation becomes unpredictable, pharmacokinetics shift, and immune dysregulation further complicates therapeutic control. Nanotechnology-based delivery systems have attempted to address these shortcomings by improving drug stability and circulation time. Yet their behavior under septic conditions remains inconsistent. This inconsistency may reflect a deeper issue: most carriers are engineered under relatively stable physiological assumptions that do not hold during systemic inflammation. Biomimetic platforms, particularly those derived from erythrocyte membranes, offer a different conceptual entry point. Rather than merely evading immune recognition, erythrocyte-based systems interact naturally with hepatic clearance pathways. During sepsis, erythrocyte turnover appears to accelerate, and macrophage-mediated clearance in the liver intensifies. This shift, while pathologic, may present a therapeutic opportunity. In this review, we examine current liver-targeted delivery strategies for sepsis-induced liver failure and critically assess the underexplored role of erythrocyte ghost-based systems. We discuss how sepsis-specific pathophysiological changes reshape carrier biodistribution, identify translational constraints, and propose design considerations for inflammation-adaptive biomimetic platforms. By reconsidering hepatic clearance not solely as a pharmacokinetic barrier but as a potential delivery route, we outline a disease-aligned approach to nanomedicine design in septic organ failure.