Abstract:
:Transient cerebral hypoperfusion (TCH) has empirically been used to assist intraarterial (IA) drug delivery to brain tumors. Transient (<3 min) reduction of cerebral blood flow (CBF) occurs during many neuro- and cardiovascular interventions and has recently been used to better target IA drugs to brain tumors. In the present experiments, we assessed whether the effectiveness of IA delivery of cationic liposomes could be improved by TCH. Cationic liposomes composed of 1:1 DOTAP:PC (dioleoyl-trimethylammonium-propane:phosphatidylcholine) were administered to three groups of Sprague-Dawley rats. In the first group, we tested the effect of blood flow reduction on IA delivery of cationic liposomes. In the second group, we compared TCH-assisted IA liposomal delivery versus intravenous (IV) administration of the same dose. In the third group, we assessed retention of cationic liposomes in brain 4 h after TCH assisted delivery. The liposomes contained a near infrared dye, DilC18(7), whose concentration could be measured in vivo by diffuse reflectance spectroscopy. IA injections of cationic liposomes during TCH increased their delivery approximately fourfold compared to injections during normal blood flow. Optical pharmacokinetic measurements revealed that relative to IV injections, IA injection of cationic liposomes during TCH produced tissue concentrations that were 100-fold greater. The cationic liposomes were retained in the brain tissue 4 h after a single IA injection. There was no gross impairment of neurological functions in surviving animals. Transient reduction in CBF significantly increased IA delivery of cationic liposomes in the brain. High concentrations of liposomes could be delivered to brain tissue after IA injections with concurrent TCH while none could be detected after IV injection. IA-TCH injections were well tolerated and cationic liposomes were retained for at least 4 h after IA administration. These results should encourage development of cationic liposomal formulations of chemotherapeutic drugs and their IA delivery during TCH.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Joshi S,Singh-Moon RP,Wang M,Chaudhuri DB,Holcomb M,Straubinger NL,Bruce JN,Bigio IJ,Straubinger RMdoi
10.1007/s11060-014-1421-6subject
Has Abstractpub_date
2014-05-01 00:00:00pages
73-82issue
1eissn
0167-594Xissn
1573-7373journal_volume
118pub_type
杂志文章abstract::The current study reports longitudinal coping responses among parents of children diagnosed with an embryonal brain tumor. Patients (n = 219) were enrolled on a treatment protocol for a pediatric embryonal brain tumor. Their parents (n = 251) completed the Coping Response Inventory at time of their child's diagnosis a...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,多中心研究
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pub_type: 临床试验,杂志文章
doi:10.1007/s11060-004-1726-y
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pub_type: 杂志文章,评审
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pub_type: 已发布勘误
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更新日期:2019-01-01 00:00:00