Safe and efficient drug delivery system with liposomes for intrathecal application of an antivasospastic drug, fasudil.
Pharmacological treatment for cerebral ischemia and cerebral vasospasm following subarachnoid hemorrhage (SAH) cannot attain sufficiently high concentrations of the drugs in the cerebrospinal fluid (CSF) without precipitating systemic side effects. We recently developed a liposomal drug delivery system for intrathecal application that can maintain effective concentrations of cerebral vasodilator, fasudil, in the CSF. A single intrathecal injection of liposomal fasudil could maintain a therapeutic drug concentration in the CSF over a period time due to their sustained-release property, significantly decreasing infarct size in a rat model of acute ischemia and reducing vasoconstriction of the rat and dog basilar artery in a model of SAH. In this review, we are introducing our new less-invasive intrathecal drug delivery system that provides an alternative and safe method to deliver therapeutic agents.
Ishida
Tatsuhiro
T
Department of Pharmacokinetics and Biopharmaceutics, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan. ishida@ph.tokushima-u.ac.jp
Takanashi
Yoshihiro
Y
Kiwada
Hiroshi
H
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006207:Half-Life; D006801:Humans; D007278:Injections, Spinal; D008081:Liposomes; D018696:Neuroprotective Agents; D012995:Solubility; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000627:therapeutic use
D004337:Drug Carriers; D008081:Liposomes; D018696:Neuroprotective Agents; D014665:Vasodilator Agents; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002784:Cholesterol; C049347:fasudil