Improving Drug Delivery to Intracerebral Tumor and Surrounding Brain in a Rodent Model: A Comparison of Osmotic versus Bradykinin Modification of the Blood-Brain and/or Blood-Tumor Barriers

Kroll, Robert A.; Pagel, Michael A.; Muldoon, Leslie L.; Roman-Goldstein, Simon; Fiamengo, Steven A.; Neuwelt, Edward A.

doi:10.1097/00006123-199810000-00090

Cited by 112 publications

(64 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…24,25 In a direct comparison, hypertonic mannitol was found to be better than bradykinin for drug delivery to rat intracerebral xenografts. 26 BBBD even enhanced the delivery of oncolytic HSV to brain tumors in rat models. 27,28 For the most part, BBBD tumor therapy studies have been performed in rats because of size considerations.…”

Section: Introductionmentioning

confidence: 99%

Intracarotid delivery of oncolytic HSV vector G47Δ to metastatic breast cancer in the brain

2005

View full text Add to dashboard Cite

Delivery of viral vectors to tumors in the brain is a challenge, especially via systemic administration, which is key to targeting the invasive margins of malignant glioma and the multiple foci of metastatic disease. Like for other cancer therapeutics, the blood-brain barrier or even the bloodtumor barrier significantly limits delivery and efficacy. Bloodbrain barrier disruption (BBBD) is one strategy for transiting the cerebrovasculature. G47D is a third-generation oncolytic replication-competent herpes simplex virus (HSV) vector, containing deletions of the g34.5 and a47 genes and an inactivating LacZ insertion in UL39 (ICP6). Intracarotid artery delivery of G47D after BBBD with 25% mannitol significantly extended the life of nude mice bearing intracerebral human MDA-MB-435 breast tumors, whereas, G47D injection contralateral to the tumor, in the absence of mannitol or mannitol alone had no effect on survival. G47D replication was extensive after BBBD, as visualized by X-gal staining. Staining of peripheral organs, lung and liver, was minimal and not altered by BBBD. This is the first demonstration of intracarotid arterial delivery of oncolytic HSV vectors and antitumor efficacy in a mouse model and opens the door to the use of mouse syngenic tumor models and transgenic/ knockout animals. Gene Therapy (2005) 12, 647-654.

show abstract

Section: Introductionmentioning

confidence: 99%

Intracarotid delivery of oncolytic HSV vector G47Δ to metastatic breast cancer in the brain

2005

View full text Add to dashboard Cite

show abstract

“…Intra-arterial mannitol can also be used to enhance drug delivery to the brain in patients with brain tumours, where it is suggested it shrinks brain microvascular endothelial cells, disrupts the tight junctions at the BBB and allows chemotherapeutic drugs to access the neural environment 6 . Along with hypertonic saline, external ventricular drainage and decompressive craniectomies, it is one of the only therapeutic interventions available for cerebral oedema, with previous studies on hypothermia and steroids having demonstrated no therapeutic benefit 7,8 .…”

mentioning

confidence: 99%

Targeted suppression of claudin-5 decreases cerebral oedema and improves cognitive outcome following traumatic brain injury

et al. 2012

View full text Add to dashboard Cite

Traumatic brain injury is the leading cause of death in children and young adults globally. malignant cerebral oedema has a major role in the pathophysiology that evolves after severe traumatic brain injury. Added to this is the significant morbidity and mortality from cerebral oedema associated with acute stroke, hypoxic ischemic coma, neurological cancers and brain infection. Therapeutic strategies to prevent cerebral oedema are limited and, if brain swelling persists, the risks of permanent brain damage or mortality are greatly exacerbated. Here we show that a temporary and size-selective modulation of the blood-brain barrier allows enhanced movement of water from the brain to the blood and significantly impacts on brain swelling. We also show cognitive improvement in mice with focal cerebral oedema following administration in these animals of short interfering RnA directed against claudin-5. These observations may have profound consequences for early intervention in cases of traumatic brain injury, or indeed any neurological condition where cerebral oedema is the hallmark pathology.

show abstract

“…The BTB, although more permeable than BBB, is still highly impermeable to most chemotherapeutic agents 16 and viral vectors without BTB disruption. 10,17 In this study, we show that the permeability of the BTB itself is sufficient to permit the specific and efficient delivery of plasmid DNA to brain tumors and STF.…”

Section: Discussionmentioning

confidence: 99%

Intra-arterial delivery of endostatin gene to brain tumors prolongs survival and alters tumor vessel ultrastructure

et al. 2004

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is an incurable malignant brain tumor, usually fatal within 1 year of diagnosis. Using a syngeneic rat 9L gliosarcoma model, we have developed a novel drug delivery method in which naked plasmid DNA is selectively targeted to brain tumors via intra-arterial injection. Using a plasmid encoding the antiangiogenic endostatin, transgene expression can be detected in tumor cells in vivo, and therapeutic efficacy is observed. Administration of this plasmid resulted in an 80% tumor volume reduction 1 week after treatment and enhanced survival time by up to 47%.Treated tumors exhibited a 40% decrease in the number of tumor vessels; ultrastructural analysis of remaining tumor vessels demonstrated a number of changes including markedly narrowed or collapsed lumens. We conclude that intra-arterial injection of plasmids selectively targets therapeutic genes to CNS neoplasms. This method of gene therapy holds promise for the treatment of these highly malignant brain tumors.

show abstract

Improving Drug Delivery to Intracerebral Tumor and Surrounding Brain in a Rodent Model: A Comparison of Osmotic versus Bradykinin Modification of the Blood-Brain and/or Blood-Tumor Barriers

Abstract: BBBD resulted in global delivery of a variety of agents in a wide range of sizes. In this human brain tumor xenograft model, bradykinin was not effective at increasing delivery to the tumor of any agent tested.

Cited by 112 publications

References 16 publications

Intracarotid delivery of oncolytic HSV vector G47Δ to metastatic breast cancer in the brain

Intracarotid delivery of oncolytic HSV vector G47Δ to metastatic breast cancer in the brain

Targeted suppression of claudin-5 decreases cerebral oedema and improves cognitive outcome following traumatic brain injury

Intra-arterial delivery of endostatin gene to brain tumors prolongs survival and alters tumor vessel ultrastructure

Contact Info

Product

Resources

About