Cerebral Hypoperfusion-Assisted Intra-arterial Deposition of Liposomes in Normal and Glioma-Bearing Rats. Issue 1 (January 2015) - Joshi, Shailendra
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. CONCLUSION: 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. ABBREVIATIONS: Chol, cholesterol DiD, DilC18 (5) DMPC, dimyristoylphosphatidylcholine DOTAP, dioleoyl-trimethylammonium-propane IA, intra-arterial MCA, middle cerebral artery OP, optical pharmacokinetic TCH, transient cerebral hypoperfusion