Toxicological Assessment of Drug-Coated Balloons

Abstract

Drug-coated balloons (DCBs) deliver antiproliferative agents -- predominantly paclitaxel -- to the arterial wall during brief balloon inflation, inhibiting neointimal hyperplasia without leaving a permanent implant. Following a 2018 meta-analysis reporting a potential late mortality signal with paclitaxel-coated devices in femoropopliteal interventions, toxicological assessment of DCBs has become a critical regulatory and clinical priority. This study presents the Drug-Coated Balloon Toxicological Assessment Framework (DCBTAF), evaluating five toxicological assessment strategies -- conventional animal histopathology, pharmacokinetic tissue distribution mapping, computational toxicity modelling, particulate embolisation quantification, and integrated multi-endpoint scoring -- across four toxicological endpoints: local arterial tissue toxicity, downstream particulate burden, systemic drug exposure, and chronic inflammatory response. Our DCB Toxicological Performance Index (DCTPI) integrates local tissue scoring, particulate safety margin, systemic exposure ratio, inflammatory burden, and long-term vessel patency. Integrated multi-endpoint scoring achieved the highest DCTPI (0.916) through simultaneous assessment of arterial injury, distal embolisation, and pharmacokinetics that captures toxicological interactions invisible to single-endpoint approaches, while computational toxicity modelling achieved the highest systemic exposure prediction accuracy (r-squared = 0.94) through physiologically-based pharmacokinetic models parameterised with DCB-specific drug transfer coefficients.