期刊
JOURNAL OF NANOPARTICLE RESEARCH
卷 15, 期 7, 页码 -出版社
SPRINGER
DOI: 10.1007/s11051-013-1772-5
关键词
Ovarian cancer; Liposomes; Paclitaxel; Topotecan; Folate receptor
资金
- University Grant Commission (UGC), Delhi
Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel-topotecan (Pac-Top; 20: 1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-alpha) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC: DMPG (85.5:9.5), DPPC: DMPG: mPEG(2000)-DSPE (85.5: 9.5:5), and DPPC: DMPG: mPEG(2000)-DSPE: DSPE-PEG-folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 +/- 0.5 degrees C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 +/- 1 degrees C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac-Top free (20:1, w/w) to be more toxic (GI(50) = 6.5 mu g/ml) than positive control (Adriamycin, GI(50) = 9.1 mu g/ml) and FR-targeted PEGylated liposomes GI(50) (14.7 mu g/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called smart liposomes which has not only mediated effective targeting to FR-alpha but also triggered release of drugs upon hyperthermia.
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