Effects of the perivascular space on convection-enhanced delivery of liposomes in primate putamen

• Published in: Experimental neurology Vol. 196; no. 1; pp. 104 - 111
• Main Authors: Krauze, Michal T., Saito, Ryuta, Noble, Charles, Bringas, John, Forsayeth, John, Mcknight, Tracy R., Park, John, Bankiewicz, Krystof S.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.11.2005; Elsevier
• Subjects: Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Convection; Convection-enhanced delivery; Drug Delivery Systems - methods; Drug toxicity and drugs side effects treatment; Fundamental and applied biological sciences. Psychology; Liposomes; Liposomes - administration & dosage; Liposomes - pharmacokinetics; Magnetic Resonance Angiography; Medical sciences; MRI; Neuropharmacology; Neuroprotective agent; Perivascular space; Pharmacology. Drug treatments; Primate; Primates; Putamen; Putamen - blood supply; Tissue Distribution; Toxicity: nervous system and muscle; Vertebrates: nervous system and sense organs; Primate; Liposomes; Convection-enhanced delivery; Perivascular space; MRI; Putamen; Human; Nervous system diseases; Fluid dynamics; Biological transport; Central nervous system; Liposome; Nuclear magnetic resonance imaging; Intracranial tumor; Convection; Cerebral disorder; Vertebrata; Mammalia; Treatment; Central nervous system disease; Primates; Clinical trial; Technique; Monitoring
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2005.07.009

Convection-enhanced delivery has recently entered the clinic and represents a promising new therapeutic option in the field of neurodegenerative diseases and treatment of brain tumors. Understanding of the principles governing delivery and flow of macromolecules within the CNS is still poorly understood and requires more investigation of the microanatomy and fluid dynamics of the brain. Our previously established, reflux-free convection-enhanced delivery (CED) technique and real-time imaging MR method for monitoring CED delivery of liposomes in primate CNS allowed us to closely monitor infusions of putamen. Our findings indicate that CED in putamen is associated with perivascular transport of liposomes, throughout CNS arteries. The results may explain side effects seen in current clinical trials using CED. In addition, they clearly show the necessity for a monitoring technique for future direct delivery of therapeutic agents to the human central nervous system. Based on these findings, we believe that the physiological concept that the perivascular space serves as a conduit for distribution of endogenous molecules within the CNS also applies to interstitially infused agents.