The method could be applied for a number of therapeutic applications. The brain-derived neurotrophic factor (BDNF) was delivered to the left hippocampus in mice through the noninvasively disrupted blood-brain barrier (BBB) using focused ultrasound. The BDNF bioactivity was found to be preserved following delivery as assessed quantitatively by immunohistochemical detection of the pTrkB receptor and activated pAkt, pMAPK, and pCREB in the hippocampal neurons.

It was shown that BDNF #BI2536 keyword# delivered this way induced signalling effects in a highly localized region in the brain [71]. However it is the area of targeting brain tumours that have attracted most interest in the FUS disrupted BBB [72]. Mei and colleagues investigated the effects of targeted and reversible disruption of the blood-brain Inhibitors,research,lifescience,medical barrier by MRI-guided focused ultrasound and delivery of methotrexate to the rabbit brain. The authors recorded that the methotrexate concentration in the sonicated group was notably higher Inhibitors,research,lifescience,medical than that in both the control group (intravenous administration) and the internal carotid artery administered group. They observed a greater than 10-fold increase in the drug level compared to internal carotid administration without FUS [73]. Liu et al. investigated the delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to glioblastomas

in rats with induced tumours with the help of FUS. The authors found that FUS significantly enhanced the penetration Inhibitors,research,lifescience,medical of BCNU through the BBB in normal and tumour-implanted brains without causing bleeding. Surprisingly, treatment of tumour-implanted rats with focused ultrasound alone had no beneficial effect on tumour progression. However, treatment with focused ultrasound before BCNU administration controlled tumour progression and improved Inhibitors,research,lifescience,medical animal survival relative to untreated controls [74]. Liu and colleagues recently assessed FUS-mediated delivery of an iron oxide magnetic nanoparticle (MNPs) conjugated to an antineoplastic agent,

epirubicin. They used MNPs because of the favourable MR imaging characteristics, which could facilitate imaging. They demonstrated a substantial accumulation of MNPs, as well as epirubicin, up to 15 times the therapeutic find more range in the brain when delivered with FUS. They further showed decreased tumour progression in animals with brain tumours that received MNP with epirubicin via FUS [75]. Receptors targeting liposomal nanocarriers have been combined with MRgFUS to treat brain tumours. In a recently presented study it was shown that pulsed HIFU and human atherosclerotic plaque-specific peptide-1- (AP-1-) conjugated liposomes containing doxorubicin (AP-1 Lipo-Dox) acted synergistically in an experimental brain tumour model.