| Title |
pH-Responsive therapeutic solid lipid nanoparticles for reducing P-glycoprotein-mediated drug efflux of multidrug resistant cancer cells
|
|---|---|
| Published in |
International Journal of Nanomedicine, August 2015
|
| DOI | 10.2147/ijn.s86053 |
| Pubmed ID | |
| Authors |
Hsin-Hung Chen, Wen-Chia Huang, Wen-Hsuan Chiang, Te-I Liu, Ming-Yin Shen, Yuan-Hung Hsu, Sung-Chyr Lin, Hsin-Cheng Chiu |
| Abstract |
In this study, a novel pH-responsive cholesterol-PEG adduct-coated solid lipid nanoparticles (C-PEG-SLNs) carrying doxorubicin (DOX) capable of overcoming multidrug resistance (MDR) breast cancer cells is presented. The DOX-loaded SLNs have a mean hydrodynamic diameter of ~100 nm and a low polydispersity index (under 0.20) with a high drug-loading efficiency ranging from 80.8% to 90.6%. The in vitro drug release profiles show that the DOX-loaded SLNs exhibit a pH-controlled drug release behavior with the maximum and minimum unloading percentages of 63.4% at pH 4.7 and 25.2% at pH 7.4, respectively. The DOX-loaded C-PEG-SLNs displayed a superior ability in inhibiting the proliferation of MCF-7/MDR cells. At a DOX concentration of 80 μM, the cell viabilities treated with C-PEG-SLNs were approximately one-third of the group treated with free DOX. The inhibition activity of C-PEG-SLNs could be attributed to the transport of C-PEG to cell membrane, leading to the change of the composition of the cell membrane and thus the inhibition of permeability glycoprotein activity. This hypothesis is supported by the confocal images showing the accumulation of DOX in the nuclei of cancer cells and the localization of C-PEG on the cell membranes. The results of in vivo study further demonstrated that the DOX delivered by the SLNs accumulates predominantly in tumor via enhanced permeability and retention effect, the enhanced passive tumor accumulation due to the loose intercellular junctions of endothelial cells lining inside blood vessels at tumor site, and the lack of lymphatic drainage. The growth of MCF-7/MDR xenografted tumor on Balb/c nude mice was inhibited to ~400 mm(3) in volume as compared with the free DOX treatment group, 1,140 mm(3), and the group treated with 1,2 distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] solid lipid nanoparticles, 820 mm(3). Analysis of the body weight of nude mice and the histology of organs and tumor after the administration of DOX-loaded SLNs show that the SLNs have no observable side effects. These results indicate that the C-PEG-SLN is a promising platform for the delivery of therapeutic agents for MDR cancer chemotherapy. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 65 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| India | 2 | 3% |
| Unknown | 63 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 17 | 26% |
| Researcher | 9 | 14% |
| Student > Master | 7 | 11% |
| Student > Postgraduate | 4 | 6% |
| Student > Bachelor | 3 | 5% |
| Other | 12 | 18% |
| Unknown | 13 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 15 | 23% |
| Medicine and Dentistry | 7 | 11% |
| Biochemistry, Genetics and Molecular Biology | 5 | 8% |
| Chemistry | 5 | 8% |
| Agricultural and Biological Sciences | 4 | 6% |
| Other | 14 | 22% |
| Unknown | 15 | 23% |
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 09 September 2015.
All research outputs
#19,944,994
of 25,374,647 outputs
Outputs from International Journal of Nanomedicine
#2,971
of 4,123 outputs
Outputs of similar age
#188,877
of 276,425 outputs
Outputs of similar age from International Journal of Nanomedicine
#118
of 141 outputs
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