Magnetic Drug Targeting Under Pulsatile Flow: A Safety-Constrained Framework for Deposition and Retention Stability

Magnetic drug targeting (MDT) is commonly evaluated by peak accumulation at the target site. Under pulsatile flow, however, initial deposition does not predict sustained localisation. We introduce the Magnetic Targeting Optimisation Concept (M-TOC), a safety-constrained framework that restructures MDT evaluation by separating geometric deposition from retention stability and embedding both within a defined hemodynamic safety window. Deposition (D) was quantified by using obstruction degree at the injection end, OD(T0), and restricted by a structural admissibility limit (OD_max = 40%). Retention stability (R) was quantified using early washout at T0 + 30 s and an apparent half-life (τ1/2) derived from coverage decay under controlled pulsatile washout. These descriptors were integrated into a Unified Targeting Score (UTS), applied only within the admissible domain, thereby enforcing feasibility before optimisation. Three PEG-functionalised magnetoresponsive nanocluster formulations were evaluated under identical magnetic and flow conditions. D–R mapping identified distinct operating regimes and showed that no tested configuration simultaneously achieved admissible deposition and robust pulsatile stability. By formalising MDT as a constrained multi-objective problem, M-TOC provides an objective method for regime discrimination and a transferable design principle for stability-guided targeting under physiological flow.