title: Cationic surface charge enhances early regional deposition of liposomes after intracarotid injection.
abstract: Rapid first pass uptake of drugs is necessary to increase tissue deposition after intraarterial (IA) injection. Here we tested whether brain tissue deposition of a nanoparticulate liposomal carrier could be enhanced by coordinated manipulation of liposome surface charge and physiological parameters, such as IA injection during transient cerebral hypoperfusion (TCH). Different degrees of blood-brain barrier disruption were induced by focused ultrasound in three sets of Sprague-Dawley rats. Brain tissue retention was then compared for anionic, cationic, and charge-neutral liposomes after IA injection combined with TCH. The liposomes contained a non-exchangeable carbocyanine membrane optical label that could be quantified using diffuse reflectance spectroscopy (DRS) or visualized by multispectral imaging. Real-time concentration-time curves in brain were obtained after each liposomal injection. Having observed greater tissue retention of cationic liposomes compared to other liposomes in all three groups, we tested uptake of cationic liposomes in C6 tumor bearing rats. DRS and multispectral imaging of postmortem sections revealed increased liposomal uptake by the C6 brain tumor as compared to non-tumor contralateral hemisphere. We conclude that regional deposition of liposomes can be enhanced without BBB disruption using IA injection of cationic liposomal formulations in healthy and C6 tumor bearing rats.
authors.affiliation: Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, 10032, USA, sj121@columbia.edu.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Joshi
authors.forename: Rajinder
authors.initials: R
authors.lastname: Singh-Moon
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Durba B
authors.initials: DB
authors.lastname: Chaudhuri
authors.forename: Jason A
authors.initials: JA
authors.lastname: Ellis
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; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology; D002232:Carbocyanines / Q000008:administration & dosage / Q000737:chemistry; D002412:Cations / Q000737:chemistry*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005240:Feasibility Studies; D007269:Injections, Intra-Arterial / Q000379:methods*; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009368:Neoplasm Transplantation; D061848:Optical Imaging; D017207:Rats, Sprague-Dawley; D013057:Spectrum Analysis; D014463:Ultrasonography / Q000379:methods
chemical_list: D002232:Carbocyanines; D002412:Cations; D008081:Liposomes