Influence of PEG Molecular Weight on Washout Resistance and Deposition Efficiency of Magnetoresponsive Nanoclusters Under Pulsatile Flow for Magnetic Drug Targeting.

Abstract

Background/Objectives: Magnetic drug targeting (MDT) using polyethene glycol (PEG)-coated magnetoresponsive nanoclusters (MNCs) can localize therapeutics, but washout from high-shear arterial flow limits efficacy. This study assesses how PEG molecular weight influences MNC deposition and washout resistance under a pulsatile flow. Methods: Magnetite MNCs were synthesized via solvothermal polyol reactions and PEGylated with PEG-2000, PEG-6000, or PEG-10,000. Characterization included TEM, DLS, zeta potential, FTIR, TGA, XPS, magnetic analysis, and rheology. In vitro assays used a 3 mm diameter glass phantom with pulsatile flow (0.10-0.45 m/s, 1 Hz) and a rectangular NdFeB (N35) permanent magnet (30 × 20 × 20 mm, 0.45 T) positioned 11 mm from the vessel wall. Washout performance was quantified by obstruction degree (OD), magnet coverage degree (MCd), washout degree (WD), washout rate constant (k_out), and half-life (τ₁/₂). Results: MNC-6000 balanced magnetic responsiveness (Ms = 72 emu/g), colloidal stability (ζ = +13.1 mV), and hydrodynamic size (535 nm), yielding superior retention (MCd = 72.3%, OD = 19.6%, WD = 17.9%, τ₁/₂ = 6.93 min). MNC-2000 exhibited faster loss (k_out = 0.14 min^-1, τ₁/₂ = 4.95 min), while MNC-10,000 produced higher OD (≈53%) with embolic risk. Magnetic mapping indicated vessel wall thresholds of B ≥ 0.18 T and ∇B ≥ 10 T/m for stable capture. Limitations: Limitations of this work include the use of a single-magnet geometry, an in vitro phantom model without endothelial biology, and a maximum targeting depth of ~12-14 mm. Conclusions: The PEG molecular weight modulates MDT performance through its effects on nanocluster stability, deposition morphology, and washout kinetics. The proposed OD, MCd, and WD metrics provide clinically relevant endpoints for optimizing MDT nanoparticle design and magnet configurations.