Ovarian cancer is the most leading cause of death and the third most common gynecologic
malignancy in women. Traditional
chemotherapy has inevitable drawbacks of nonspecific
tumor targeting, high toxicity, and poor therapeutic efficiency. In order to overcome such shortcomings, we prepared a novel nano-carrier drug-delivery system to enhance the anti-
tumor efficiency.
METHODS: In vitro characterizations of nano-carriers were determined by TEM, DLS. Cell viability was measured by MTT method. RT-PCR was performed to measure the expression of FARĪ± in three
ovarian cancer cell lines. The drug-release study and the uptaken study were measured in vitro. The pharmacokinetic and the
drug distribution study were verified by HPLC methods in vivo. The enhanced anti-
tumor efficiency of FA-NP was evaluated by the
tumor inhibitory rate in vivo.
RESULTS:
Paclitaxel (PTX)-loaded nanoparticles (NPs) (PTX-
PEG-PLA-NP and PTX-
PEG-PLA-FA-NP) were prepared successfully, and the drug-release study showed that the cumulative release rates of NP groups were much less than free PTX group. The pharmacokinetic study showed that the elimination phase of two kinds of NP groups were much longer than that of PTX group. The
drug distribution in different tissues showed that the peak-reach time was 2 h in the PTX group and 6 h in both NP groups. All of these results confirmed the excellent slow-release effects of both kinds of nano-carriers. More importantly, we confirmed that PTX-
PEG-PLA-FA-NP had greater uptake by SK-OV-3 cells than PTX-
PEG-PLA-NP and free PTX in vitro. A
drug-distribution study of
tumor-bearing mice demonstrated that the PTX concentration of
tumor tissues in the PTX-
PEG-PLA-FA-NP group was 3 times higher than the other two groups. PTX-
PEG-PLA-FA-NP was uptaken much more by SK-OV-3 cells than PTX-
PEG-PLA-NP and free PTX. Eventually, based on the slow-release effect and
tumor-targeting characteristics of PTX-
PEG-PLA-FA-NP, a cytotoxicity test indicated that PTX-
PEG-PLA-FA-NP was much more toxic to SK-OV-3 cells than the controls. The
tumor inhibitory rate in the PTX-
PEG-PLA-FA-NP group of
tumor-bearing mice was about 1.5 times higher than the controls. The
tumor targeting and anti-
tumor efficiency of PTX-
PEG-PLA-FA-NP were confirmed both in vitro and in vivo.
CONCLUSIONS: