title: Cationizable lipid micelles as vehicles for intraarterial glioma treatment.
abstract: The relative abundance of anionic lipids on the surface of endothelia and on glioma cells suggests a workable strategy for selective drug delivery by utilizing cationic nanoparticles. Furthermore, the extracellular pH of gliomas is relatively acidic suggesting that tumor selectivity could be further enhanced if nanoparticles can be designed to cationize in such an environment. With these motivating hypotheses the objective of this study was to determine whether nanoparticulate (20 nm) micelles could be designed to improve their deposition within gliomas in an animal model. To test this, we performed intra-arterial injection of micelles labeled with an optically quantifiable dye. We observed significantly greater deposition (end-tissue concentration) of cationizable micelles as compared to non-ionizable micelles in the ipsilateral hemisphere of normal brains. More importantly, we noted enhanced deposition of cationizable as compared to non-ionizable micelles in glioma tissue as judged by semiquantitative fluorescence analysis. Micelles were generally able to penetrate to the core of the gliomas tested. Thus we conclude that cationizable micelles may be constructed as vehicles for facilitating glioma-selective delivery of compounds after intraarterial injection.
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Juliane
authors.initials: J
authors.lastname: Nguyen
authors.affiliation: Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA.
authors.forename: Johann R N
authors.initials: JRN
authors.lastname: Cooke
authors.affiliation: Department of Neurological Surgery, Columbia University, New York, NY, USA. jae2109@columbia.edu.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Ellis
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Deci
authors.affiliation: Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Emala
authors.affiliation: Department of Neurological Surgery, Columbia University, New York, NY, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bruce
authors.affiliation: Department of Electrical Engineering, Boston University, Boston, MA, USA.|Department of Biomedical Engineering, Boston University, Boston, MA, USA.
authors.forename: Irving J
authors.initials: IJ
authors.lastname: Bigio
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.|Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Straubinger
authors.affiliation: Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Joshi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes; D005910:Glioma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D007269:Injections, Intra-Arterial; D008823:Micelles; D009368:Neoplasm Transplantation; D061848:Optical Imaging; D011092:Polyethylene Glycols; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013057:Spectrum Analysis
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D005456:Fluorescent Dyes; D008823:Micelles; D011092:Polyethylene Glycols
keywords: Blood–brain barrier; Brain tumor; Chemotherapy; Glioma; Nanoparticle