Focused ultrasound-induced blood–brain barrier disruption enhances the delivery of cytarabine to the rat brain

Abstract

To investigate the feasibility of using focused ultrasound (FUS) with microbubbles for targeted delivery of cytarabine to the brain. Sprague–Dawly rats (weighing 200–250 g) received focused ultrasound with intravenous injection microbubbles. At 0, 2, 4, 8, and 24 hours (n = 5 for each time point) after sonication, animals received intravenous administration of cytarabine at a normal dose of 4 mg/kg body weight. Additional five rats were given with a high dose (50 mg/kg body weight) of cytarabine alone. Blood–brain barrier (BBB) permeability and cerebral cytarabine were determined. FUS in conjunction with microbubbles caused a transient BBB opening. Sonication exposure promoted cytarabine accumulation at the sonicated site. Animals injected with a normal dose of cytarabine 2 hours after sonication had similar concentrations of cerebral cytarabine compared to those with higher cytarabine without sonication. FUS can temporarily open the BBB and thus facilitate the penetration of systemic cytarabine into the brain.

Keywords:

• Blood–brain barrier
• Cytarabine
• Focused ultrasound
• Microbubble
• Rat