Magnetic resonance monitoring of focused ultrasound/magnetic nanoparticle targeting delivery of therapeutic agents to the brain

Abstract

The superparamagnetic properties of magnetic nanoparticles (MNPs) allow them to be guided by an externally positioned magnet and also provide contrast for MRI. However, their therapeutic use in treating CNS pathologies in vivo is limited by insufficient local accumulation and retention resulting from their inability to traverse biological barriers. The combined use of focused ultrasound and magnetic targeting synergistically delivers therapeutic MNPs across the blood-brain barrier to enter the brain both passively and actively. Therapeutic MNPs were characterized and evaluated both in vitro and in vivo, and MRI was used to monitor and quantify their distribution in vivo. The technique could be used in normal brains or in those with tumors, and significantly increased the deposition of therapeutic MNPs in brains with intact or compromised blood-brain barriers. Synergistic targeting and image monitoring are powerful techniques for the delivery of macromolecular chemotherapeutic agents into the CNS under the guidance of MRI.blood-brain barrier | brain drug delivery | focused ultrasound | magnetic nanoparticles | magnetic targeting

In vivo MR quantification of superparamagnetic iron oxide nanoparticle leakage during low‐frequency‐ultrasound‐induced blood–brain barrier opening in swine

“…Also, because SPIO nanoparticles respond to external magnetic forces, magnetic targeting can actively enhance their deposition at the target site, increasing the therapeutic dose delivered beyond that obtainable by passive diffusion into BBB-disrupted regions. It has been demonstrated that conjugating SPIO with a chemotherapeutic agent can treat brain tumors in rodents (34,35). SPIO proved effective both as an image indicator (to identify distribution of chemotherapeutic drugs after BBB disruption) and as a means of increasing treatment efficacy when used in conjunction with magnetic targeting.…”

Magnetic nanoparticle drug delivery systems for targeting tumor

“…However, on application of external magnet, approximately 15-fold higher than the therapeutic range of epirubicin per gram of tissue were taken up by tumor cells. The confocal and fluorescence microscopy and Prussian blue staining further confirmed the presence of more epirubicin-MNPs at the tumor site than in the contralateral side (Liu et al 2010).…”

“…However, EPR can be limited by environment of the tumor, such as hypovascularity, fibrosis, or necrosis even when pathologic processes compromise the integrity or function of the BBB (Kreuter 2001;Lockman et al 2002;Pardridge 2002). Towards this end, Liu et al developed MNPs of iron oxide (Fe 3 O 4 ) by encapsulating them within the polymer poly[aniline-co-N-(1-one-butyric acid)] aniline (SPAnH) (Liu et al 2010). The anticancer agent epirubicin was immobilized on the surface of these MNPs.…”

Noninvasive and Targeted Drug Delivery to the Brain Using Focused Ultrasound

“…70 Histological detection of apoptosis inducing factors suggests the cells remain bioactive after delivery through the BBB. Delivery of other chemotherapeutic agents including 1,3-bis(2-chloroethyl)-1-nitrosurea (BCNU), 71,72 epirubicin, 73 and doxorubicin 74,75 have all resulted in decreased tumor growth and improved animal survival. There has also been interest in using FUS for treatment of Alzheimer's disease (AD).…”