| Title |
The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance
|
|---|---|
| Published in |
International Journal of Nanomedicine, January 2013
|
| DOI | 10.2147/ijn.s38737 |
| Pubmed ID | |
| Authors |
Chung Ping Leon Wan, Kevin Letchford, John K Jackson, Helen M Burt |
| Abstract |
Two types of nanoparticles were prepared using the diblock copolymer methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-b-PCL), with either a short PCL block length, which forms micelles, or with a longer PCL block length, which forms kinetically "frozen core" structures termed nanospheres. Paclitaxel (PTX)-loaded micelles and nanospheres were evaluated for their cytotoxicity, cellular polymer uptake, and drug accumulation in drug-sensitive (Madin-Darby Canine Kidney [MDCK]II) and multidrug-resistant (MDR) P-glycoprotein (P-gp)-overexpressing (MDCKII-MDR1) cell lines. Both types of PTX-loaded nanoparticles were equally effective at inhibiting proliferation of MDCKII cells, but PTX-loaded micelles were more cytotoxic than nanospheres in MDCKII-MDR1 cells. The intracellular accumulation of both PTX and the diblock copolymers were similar for both nanoparticles, suggesting that the difference in cytotoxicity might be due to the different drug-release profiles. Furthermore, the cytotoxicity of these PTX-loaded nanoparticles was enhanced when these systems were subsequently or concurrently combined with a low-molecular-weight MePEG-b-PCL diblock copolymer, which we have previously demonstrated to be an effective P-gp inhibitor. These results suggest that the dual functionality of MePEG-b-PCL might be useful in delivering drug intracellularly and in modulating P-gp in order to optimize the cytotoxicity of PTX in multidrug-resistant cells. |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Korea, Republic of | 1 | 4% |
| Unknown | 23 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 9 | 38% |
| Researcher | 3 | 13% |
| Student > Bachelor | 3 | 13% |
| Student > Doctoral Student | 2 | 8% |
| Student > Master | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 5 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 6 | 25% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 17% |
| Chemistry | 3 | 13% |
| Medicine and Dentistry | 3 | 13% |
| Psychology | 1 | 4% |
| Other | 2 | 8% |
| Unknown | 5 | 21% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 January 2013.
All research outputs
#22,760,732
of 25,374,917 outputs
Outputs from International Journal of Nanomedicine
#3,598
of 4,122 outputs
Outputs of similar age
#258,419
of 289,007 outputs
Outputs of similar age from International Journal of Nanomedicine
#55
of 64 outputs
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