| Title |
Pharmacokinetics and in vitro/in vivo antitumor efficacy of aptamer-targeted Ecoflex® nanoparticles for docetaxel delivery in ovarian cancer
|
|---|---|
| Published in |
International Journal of Nanomedicine, January 2018
|
| DOI | 10.2147/ijn.s152474 |
| Pubmed ID | |
| Authors |
Erfaneh Ghassami, Jaleh Varshosaz, Ali Jahanian-Najafabadi, Mohsen Minaiyan, Parvin Rajabi, Effat Hayati |
| Abstract |
Epithelixal ovarian cancer is the fourth cause of cancer death in developed countries with 77% of ovarian cancer cases diagnosed with regional or distant metastasis, with poor survival rates. Docetaxel (DTX) is a well-known anticancer agent, with clinically proven efficacy in several malignancies, including ovarian cancer. However, the adverse effects caused by the active ingredient or currently marketed formulations could even deprive the patient of the advantages of treatment. Therefore, in the current study, polymeric nanoparticles (NPs) equipped with aptamer molecules as targeting agents were proposed to minimize the adverse effects and enhance the antitumor efficacy through directing the drug cargo toward its site of action. Electrospraying technique was implemented to fabricate poly (butylene adipate-co-butylene terephthalate) (Ecoflex®) NPs loaded with DTX (DTX-NPs). Afterward, aptamer molecules were added to the DTX-NPs, which bound via covalent bonds (Apt-DTX-NPs). The particle size, size distribution, zeta potential, entrapment efficiency, and release profile of the NPs were characterized. Using MTT assay and flow-cytometry analysis, the in vitro cytotoxicity and cellular uptake of the NPs were compared to those of the free drug. Following intravenous administration of Taxotere®, DTX-NPs, and Apt-DTX-NPs (at an equivalent dose of 5 mg/kg of DTX), pharmacokinetic parameters and antitumor efficacy were compared in female Balb/c and HER-2-overexpressing tumor-bearing B6 athymic mice, respectively. The obtained results demonstrated significantly enhanced in vitro cytotoxicity and cellular uptake of Apt-DTX-NPs in a HER-2-overexpressing cell line, comparing to DTX-NPs and the free drug. The results of in vivo studies indicated significant increment in pharmacokinetic parameters including the area under the plasma concentration-time curve, mean residence time, and elimination half-life. Significant increment in antitumor efficacy was also observed, probably due to the targeted delivery of DTX to the tumor site and enhanced cellular uptake as evaluated in the aforementioned tests. Hence, the proposed drug delivery system could be considered as an appropriate potential substitute for currently marketed DTX formulations. |
Mendeley readers
The data shown below were compiled from readership statistics for 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 50 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 7 | 14% |
| Student > Ph. D. Student | 7 | 14% |
| Student > Master | 5 | 10% |
| Researcher | 5 | 10% |
| Professor | 1 | 2% |
| Other | 1 | 2% |
| Unknown | 24 | 48% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 6 | 12% |
| Engineering | 5 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 8% |
| Medicine and Dentistry | 4 | 8% |
| Computer Science | 1 | 2% |
| Other | 6 | 12% |
| Unknown | 24 | 48% |
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 13 March 2018.
All research outputs
#22,767,715
of 25,382,440 outputs
Outputs from International Journal of Nanomedicine
#3,598
of 4,122 outputs
Outputs of similar age
#389,382
of 449,550 outputs
Outputs of similar age from International Journal of Nanomedicine
#56
of 65 outputs
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