High payload dual therapeutic-imaging nanocarriers for triggered tumor delivery.
The in vitro and in vivo characterization of an optimized formulation of nanoparticles (NPs) loaded with a high content of dexamethasone palmitate (DEX-P), a chemotherapeutic adjuvant that decreases interstitial fluid pressure in tumors, and (111) In, a signaling agent, is described. These NPs are uniform in size and composition. Single photon emission computed tomography imaging demonstrates significant tumor uptake of (111) In-labeled DEX-P NPs in tumor-bearing mice. As with many nanoparticle-based drug delivery systems, significant liver accumulation is observed. Assessment of liver histology and blood tests show no apparent hepatic or renal toxicity of the DEX-P NPs. Conversion of DEX-P to DEX occurs when DEX-P NPs are incubated with mouse plasma, human tumor homogenate and ascites from tumor bearing mice, but not with human plasma. This conversion is slower in plasma from Es1(e)             ((-/-)) /SCID mice, a potential alternative animal model that better mimics humans; however, plasma from these mice are not completely devoid of esterase activity. The difference between blood and tumor esterase activity in humans facilitates the delivery of DEX-P NPs to tumors and the release of dexamethasone by an esterase trigger.
Division of Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy and Lineberger, Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Jin-Ki
JK
Kim
Hong
H
Yuan
Jingxin
J
Nie
Yu-Tsai
YT
Yang
Markos
M
Leggas
Philip M
PM
Potter
John
J
Rinehart
Michael
M
Jay
Xiuling
X
Lu
D000818:Animals; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D015899:Tomography, Emission-Computed, Single-Photon; D014183:Transplantation, Heterologous
D004337:Drug Carriers; D007205:Indium Radioisotopes; D011355:Prodrugs; D019275:Radiopharmaceuticals; D003907:Dexamethasone