Related Experiment Videos
[The effect on the tumor vessel permeability by hyperosmotic blood brain barrier disruption]
M Miyagami1, M Tazoe, Y Kagawa
1Department of Neurological Surgery, School of Medicine, Nihon University, Tokyo, Japan.
Abstract:
The limited effect of chemotherapy on malignant brain tumors has been related to tumor cell insensitivity to the drugs and to their ineffectual delivery to the tumor. The studies by Groothuis and Neuwelt et al have shown that the studies of tumor vessel permeability show considerable variability in different areas of tumors and between different tumor models. The present studies used the 9L gliosarcoma model in Fischer 344 rats to evaluate the increase of tumor vessel permeability by osmotic BBB opening on drug delivery to the tumor, brain adjacent to tumor (BAT), and brain distant to tumor using cis-diamminedichloroplatinum (CDDP) as a chemotherapeutic agent which was water soluble and rarely permeable to BBB. In addition the difference of delivery to normal brain and tumor tissue were studied on intravenous or intracarotid administration of cisplatin with or without intracarotid infusion of graded (20%, 25%) hyperosmolar mannitol. Evans blue, which binds to plasma albumin, was used to provide a visual marker of BBB opening. 20% or 25% hyperosmolar mannitol infusion to right internal carotid artery for BBB disruption was done at 0.12 ml/sec for 30 sec with controlled respiration after temporally clipping of right common carotid artery. Then cis-diamminedichloroplatinum (CDDP) was infused at 0.5 mg/ml/100 gr (body weight). In control studies isotonic saline instead of mannitol was infused to intracarotid artery at identical rate and volume. In 14 9L gliosarcoma bearing rats and 3 normal rats cis-diamminedichloroplatinum (CDDP) delivery to tumor and normal brain.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Osmotic blood-brain barrier opening enhances chemotherapy delivery to brain tumors. This method improves drug distribution in tumor tissues, offering a potential strategy to overcome treatment resistance in malignant brain tumors.
Area of Science:
- Neuro-oncology
- Pharmacology
- Biomedical Engineering
Context:
- Malignant brain tumors are challenging to treat due to chemotherapy's limited efficacy.
- Poor drug delivery across the blood-brain barrier (BBB) and tumor cell insensitivity contribute to treatment failure.
- Tumor vessel permeability varies significantly, complicating drug distribution.
Purpose:
- To evaluate the impact of osmotic BBB opening on the delivery of cisplatin (CDDP) to malignant brain tumors (9L gliosarcoma model in rats).
- To compare drug delivery to the tumor, brain adjacent to tumor (BAT), and distant normal brain tissue.
- To assess the influence of intracarotid mannitol infusion on cisplatin distribution.
Summary:
- The study utilized a 9L gliosarcoma rat model to investigate enhanced drug delivery via osmotic BBB disruption.
- Intracarotid infusion of hyperosmolar mannitol (20-25%) was used to open the BBB, followed by cisplatin administration.
- Evans blue was employed to visualize BBB opening, and cisplatin delivery to tumor and normal brain was quantified.
Impact:
- Demonstrates that osmotic BBB opening significantly increases chemotherapeutic agent delivery to brain tumors.
- Highlights the potential of BBB disruption techniques to improve the efficacy of chemotherapy for brain cancers.
- Provides insights into differential drug distribution between tumor and normal brain tissue following BBB opening.