Abstract
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 111In, a signaling agent, is described. These NPs are uniform in size and composition. Single photon emission computed tomography imaging demonstrates significant tumor uptake of 111In-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. Homogeneous dual therapeutic-imaging nanocarriers containing a chemotherapeutic adjuvant, dexamethasone palmitate (DEX-P), and a signaling agent, 111In, exhibit significant tumor uptake in single photon emission computed tomography images. High esterase activity in tumors, but not in human plasma, facilitates the esterolysis of the prodrug DEX-P resulting in the intra-tumoral release of DEX from DEX-P nanoparticles.
Original language | English |
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Pages (from-to) | 2895-2903 |
Number of pages | 9 |
Journal | Small |
Volume | 8 |
Issue number | 18 |
DOIs | |
State | Published - Sep 24 2012 |
Keywords
- SPECT/CT imaging
- dexamethasone
- ester prodrug
- nanoparticles
- triggered release
ASJC Scopus subject areas
- Biotechnology
- General Chemistry
- Biomaterials
- General Materials Science
- Engineering (miscellaneous)