Intranasal administration of temozolomide combined with focused ultrasound to enhance the survival of mice with glioma (A Pilot Study)

Intranasal route provides therapeutics direct access to the brain through the nose-to-brain pathway, bypassing the BBB and minimizing systemic exposure. However, nasal delivery is limited by its low delivery efficiency and non-localized delivery. Focused ultrasound-enhanced intranasal (FUSIN) delivery is a new technique for noninvasive and localized delivery of therapeutic agents to the brain. Previous studies have shown its feasibility in the delivery of dextrans and brain-derived neurotrophic factor to the brain. The goal of this study was to demonstrate the application of FUSIN for the delivery of temozolomide (TMZ), a first-line drug for treating glioma tumors, for the treatment of glioblastoma in an orthotopic mouse model. U87 glioblastoma cells were trancranially implanted to nude mice. The tumor mice were divided into four groups: (1) FUSIN + TMZ (n = 7); (2) IN TMZ (n = 6); (3) Oral TMZ (n = 6); and (4) IN vehicle (n = 6), and were treated once each week for 4 weeks. Mice were weighed once a week. A body weight loss reaching 20% was selected as the endpoint criteria for the study. Mice in FUSIN group showed statistically significant higher survival rate when compared with mice in all other groups. This pilot study suggested that FUSIN can potentially be an effective technique for the treatment of brain diseases.Intranasal route provides therapeutics direct access to the brain through the nose-to-brain pathway, bypassing the BBB and minimizing systemic exposure. However, nasal delivery is limited by its low delivery efficiency and non-localized delivery. Focused ultrasound-enhanced intranasal (FUSIN) delivery is a new technique for noninvasive and localized delivery of therapeutic agents to the brain. Previous studies have shown its feasibility in the delivery of dextrans and brain-derived neurotrophic factor to the brain. The goal of this study was to demonstrate the application of FUSIN for the delivery of temozolomide (TMZ), a first-line drug for treating glioma tumors, for the treatment of glioblastoma in an orthotopic mouse model. U87 glioblastoma cells were trancranially implanted to nude mice. The tumor mice were divided into four groups: (1) FUSIN + TMZ (n = 7); (2) IN TMZ (n = 6); (3) Oral TMZ (n = 6); and (4) IN vehicle (n = 6), and were treated once each week for 4 weeks. Mice were weighed once a week....