期刊
JOURNAL OF CONTROLLED RELEASE
卷 164, 期 2, 页码 170-176出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2012.04.042
关键词
Polymeric nanoparticles; Drug delivery; Drug release; Cellular uptake; Bioactivity
资金
- NIH [R21 CA135130]
- NSF [DMR-1056997]
- P.E.O. Scholar Award
- Bilsland Dissertation Fellowship
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [1056997] Funding Source: National Science Foundation
Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) conjugated to a cell-penetrating peptide, TAT, was used to increase intracellular delivery of paclitaxel (PTX) to multi-drug resistant (MDR) cells. Efficient cellular uptake of the TAT-conjugated PLGA NPs was observed; however, it did not translate to increased killing of MDR cells. An investigation of drug release kinetics in phosphate-buffered saline containing Tween 80 led us to suspect that a significant fraction of the loaded PTX was released before efficient cellular uptake could occur. These results indicate that the increased cellular uptake of NPs does not always mean an enhanced drug effect and that it is critical to control both the location of NPs and the drug release from NPs together. Based on this study, we propose that two prevalent practices in NP research be reconsidered: first, the utility of a new NP system should be tested beyond the imaging level. Second, NP release kinetics should be monitored in a medium that can reflect the complexity of biological environment rather than a simple buffered saline. (C) 2012 Elsevier B.V. All rights reserved.
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