Liposome size and charge optimization for intraarterial delivery to gliomas.
Nanoparticles such as liposomes may be used as drug delivery vehicles for brain tumor therapy. Particle geometry and electrostatic properties have been hypothesized to be important determinants of effective tumor targeting after intraarterial injection. In this study, we investigate the combined roles of liposome size and surface charge on the effectiveness of delivery to gliomas after intraarterial injection. Intracarotid injection of liposomes was performed in separate cohorts of both healthy and C6 glioma-bearing Sprague Dawley rats after induction of transient cerebral hypoperfusion. Large (200 nm) and small (60-80 nm) fluorescent dye-loaded liposomes that were either cationic or neutral in surface charge were utilized. Delivery effectiveness was quantitatively measured both with real-time, in vivo and postmortem diffuse reflectance spectroscopy. Semi-quantitative multispectral fluorescence imaging was also utilized to assess the pattern and extent of liposome targeting within tumors. Large cationic liposomes demonstrated the most effective hemispheric and glioma targeting of all the liposomes tested. Selective large cationic liposome retention at the site of glioma growth was observed. The liposome deposition pattern within tumors after intraarterial injection was variable with both core penetration and peripheral deposition observed in specific tumors. This study provides evidence that liposome size and charge are important determinants of effective brain and glioma targeting after intraarterial injection. Our results support the future development of 200-nm cationic liposomal formulations of candidate intraarterial anti-glioma agents for further pre-clinical testing.
Department of Anesthesiology, Columbia University Medical Center, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA. sj121@cumc.columbia.edu.
Shailendra
S
Joshi
Department of Anesthesiology, Columbia University Medical Center, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA.
Johann R N
JR
Cooke
Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Darren K W
DK
Chan
Department of Neurological Surgery, Columbia University Medical Center, New York, NY, USA.
Jason A
JA
Ellis
Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA.|Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, TX, USA.
Shaolie S
SS
Hossain
Department of Electrical Engineering, Columbia University, New York, NY, USA.
Rajinder P
RP
Singh-Moon
Department of Anesthesiology, Columbia University Medical Center, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA.
Mei
M
Wang
Department of Electrical Engineering and Biomedical Engineering, Boston University, Boston, MA, USA.
Irving J
IJ
Bigio
Department of Neurological Surgery, Columbia University Medical Center, New York, NY, USA.
Jeffrey N
JN
Bruce
Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.|Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA.
Robert M
RM
Straubinger
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005910:Glioma / Q000378:metabolism*; D007269:Injections, Intra-Arterial; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D061848:Optical Imaging; D010316:Particle Size; D051381:Rats; D013499:Surface Properties
D008081:Liposomes
Brain tumor; Chemotherapy; Glioblastoma; Nanoparticle