Development of a Personalised Device for Systemic Magnetic Drug Targeting to Brain Tumours

Abstract

Delivering therapies to deeply seated brain tumours (BT) is a major clinical challenge. Magnetic drug targeting (MDT) could overcome this by rapidly transporting magnetised drugs directly into BT. We have developed a magnetic device for application in murine BT models using an array of neodymium magnets with a combined strength of 0.7T. In a closed fluidic system, the magnetic device trapped magnetic nanoparticles (MNP) up to distances of 0.8cm. In mice, the magnetic device guided intravenously administered MNP (<50nm) from the circulation into the brain where they localised within mouse BT. Furthermore, MDT of magnetised Temozolomide (TMZ mag+ ) significantly reduced tumour growth and extended mouse survival to 48 days compared to the other treatment groups. Using the same principles, we built a proof of principle scalable magnetic device for human use with a strength of 1.1T. This magnetic device demonstrated trapping of MNP undergoing flow at distances up to 5cm. MDT using our magnetic device provides an opportunity for targeted delivery of magnetised drugs to human BT.

How the Magnetization Angle of a Linear Halbach Array Influences Particle Steering in Magnetic Drug Targeting—A Systematic Evaluation and Optimization

“…Moreover, since the movement of the particles depends on the equilibrium of forces (Equation ( 5)), the magnitude of the drag force |F d | must also be taken into account. However, this is not the case in many studies [32,42,45,54,99,104]. For this reason, the reliability of these findings should also be treated with care.…”

“…Therefore, in other papers, the gradient of H or B is also analyzed [17,25,31,32,47]. Other researchers evaluated the magnetic force F m [32,42,45,54,99,104]. Nevertheless, the gradients and F m are usually analyzed at predefined evaluation positions, but, as shown in our previous paper [51], the magnitude of F m strongly depends on the evaluation position.…”

“…In Table 6, an overview of the evaluated parameters is provided. Here, e. g., the magnitude of the magnetic field | ⃗ H| and magnetic flux density | ⃗ B| are evaluated [16,25,31,36,42,54,99,105,106]. However, as Equation ( 8) depicts, the magnetic force is directly proportional to the gradient of B.…”

“…Furthermore, in most publications (including our paper), the distance between the magnetic field source and the vessel is within only a few centimeters (or less), quite short. Surpi et al [36] varied the distance up to 0.5 cm, Kee et al [104] and Shiriny et al [54] up to 1 cm, Patel et al [42] up to 1.5 cm, Sarraf et al [105] up to 2.5 cm, Bernad et al [99] up to 3 cm, and Chakrabarty et al [16] plus Liu et al [45] up to 4 cm. Only Camargo et al [107] investigated greater distances up to 7.5 cm.…”

“…In the literature, different types of arrays, mostly entirely consisting of PMs [42,43] but also of EMs [44], as well as hybrid ones [45,46], are discussed. The arrays are arranged linearly and parallel to the vessel [47] as well as coaxial structures surrounding the vessel [37].…”