Effect of circadian rhythm modulated blood flow on nanoparticle based targeted drug delivery in virtual in vivo arterial geometries

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 (kout), 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 (kout = 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.

Advances in nanoparticles in targeted drug delivery–A review

Pharmaceutical 3D printing, combined with nanomaterials and nanodevices, presents a transformative approach to precision medicine for treating neurological diseases. This technology enables the creation of tailored dosage forms with controlled release profiles, enhancing drug delivery across the blood-brain barrier (BBB). The integration of nanoparticles, such as poly lactic-co-glycolic acid (PLGA), chitosan, and metallic nanomaterials, into 3D-printed scaffolds improves treatment efficacy by providing targeted and prolonged drug release. Recent advances have demonstrated the potential of these systems in treating conditions like Parkinson's disease, epilepsy, and brain tumors. Moreover, 3D printing allows for multi-drug combinations and personalized formulations that adapt to individual patient needs. Novel drug delivery approaches, including stimuli-responsive systems, on-demand dosing, and theragnostics, provide new possibilities for the real-time monitoring and treatment of neurological disorders. Despite these innovations, challenges remain in terms of scalability, regulatory approval, and long-term safety. The future perspectives of this technology suggest its potential to revolutionize neurological treatments by offering patient-specific therapies, improved drug penetration, and enhanced treatment outcomes. This review discusses the current state, applications, and transformative potential of 3D printing and nanotechnology in neurological treatment, highlighting the need for further research to overcome the existing challenges.