title: Cerebral hypoperfusion-assisted intra-arterial deposition of liposomes in normal and glioma-bearing rats.
abstract: BACKGROUND
  Optimizing liposomal vehicles for targeted delivery to the brain has important implications for the treatment of brain tumors. The promise of efficient, brain-specific delivery of chemotherapeutic compounds via liposomal vehicles has yet to be achieved in clinical practice. Intra-arterial injection of specially designed liposomes may facilitate efficient delivery to the brain and to gliomas.
  
  
  OBJECTIVE
  To test the hypothesis that cationic liposomes may be effectively delivered to both normal and glioma-bearing brain tissue utilizing a strategy of intra-arterial injection during transient cerebral hypoperfusion.
  
  
  METHODS
  Cationic, anionic, and neutral liposomes were separately injected via the internal carotid artery of healthy rats during transient cerebral hypoperfusion. Rats bearing C6 gliomas were similarly injected with cationic liposomes. Liposomes were loaded with DilC18(5) dye whose concentrations can be measured by light absorbance and fluorescence methods.
  
  
  RESULTS
  After intra-arterial injection, a robust uptake of cationic in comparison with anionic and neutral liposomes into brain parenchyma was observed by diffuse reflectance spectroscopy. Postmortem multispectral fluorescence imaging revealed that liposomal cationic charge was associated with more efficient delivery to the brain. Cationic liposomes were also readily observed within glioma tissue after intra-arterial injection. However, over time, cationic liposomes were retained longer and at higher concentrations in the surrounding, peritumoral brain than in the tumor core.
  
  
  CONCLUSIONS
  This study demonstrates the feasibility of cationic liposome delivery to brain and glioma tissue after intra-arterial injection. Highly cationic liposomes directly delivered to the brain via an intracarotid route may represent an effective method for delivering antiglioma agents.
authors.affiliation: *Department of Anesthesiology, Columbia University, College of Physicians and Surgeons, New York, New York; ‡Department of Neurological Surgery, Columbia University Medical Center, New York, New York; §Department of Electrical Engineering, Boston University, Boston, Massachusetts; ¶Department of Bioengineering, University of Washington, Seattle, Washington; ‖Department of Biomedical Engineering, Boston University, Boston, Massachusetts #Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York; **Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Joshi
authors.forename: Rajinder P
authors.initials: RP
authors.lastname: Singh-Moon
authors.forename: Jason A
authors.initials: JA
authors.lastname: Ellis
authors.forename: Durba B
authors.initials: DB
authors.lastname: Chaudhuri
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Roberto
authors.initials: R
authors.lastname: Reif
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bruce
authors.forename: Irving J
authors.initials: IJ
authors.lastname: Bigio
authors.forename: Robert M
authors.initials: RM
authors.lastname: Straubinger
mesh_terms: D000818:Animals; D000838:Anions; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002412:Cations; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D005910:Glioma / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007269:Injections, Intra-Arterial; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000503:physiopathology*; D008081:Liposomes / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000838:Anions; D002412:Cations; D008081:Liposomes