26 research outputs found
Development of Liposomal Formulation for Delivering Anticancer Drug to Breast Cancer Stem-Cell-Like Cells and its Pharmacokinetics in an Animal Model
The
objective of the present study is to develop a liposomal formulation
for delivering anticancer drug to breast cancer stem-cell-like cells,
ANV-1, and evaluate its pharmacokinetics in an animal model. The anticancer
drug ESC8 was used in dexamethasone (Dex)-associated liposome (DX)
to form ESC8-entrapped liposome named DXE. ANV-1 cells showed high-level
expression of NRP-1. To enhance tumor regression, we additionally
adapted to codeliver the NRP-1 shRNA-encoded plasmid using the established
DXE liposome. In vivo efficacy of DXE-NRP-1 was carried out in mice
bearing ANV-1 cells as xenograft tumors and the extent of tumor growth
inhibition was evaluated by tumor-size measurement. A significant
difference in tumor volume started to reveal between DXE-NRP-1 group
and DXE-Control group. DXE-NRP-1 group showed ∼4 folds and
∼2.5 folds smaller tumor volume than exhibited by untreated
and DXE-Control-treated groups, respectively. DXE disposition was
evaluated in Sprague–Dawley rats following an intraperitoneal
dose (3.67 mg/kg of ESC8 in DXE). The plasma concentrations of ESC8
in the DXE formulation were measured by liquid chromatography mass
spectrometry and pharmacokinetic parameters were determined using
a noncompartmental analysis. ESC8 had a half-life of 11.01 ±
0.29 h, clearance of 2.10 ± 3.63 L/kg/h, and volume of distribution
of 33.42 ± 0.83 L/kg. This suggests that the DXE liposome formulation
could be administered once or twice daily for therapeutic efficacy.
In overall, we developed a potent liposomal formulation with favorable
pharmacokinetic and tumor regressing profile that could sensitize
and kill highly aggressive and drug-resistive cancer stem-cell-like
cells
Clinical and biochemical parameters of study subjects by group.
<p>Data represented by mean ± standard deviation;</p>a<p>indicates group significantly different from control;</p>b<p>indicates group significantly different from obese without diabetes;</p>c<p>indicates group significantly different from non-obese diabetes;</p>d<p>indicates group significantly different from obese diabetes. Level of significance is given at p≤0.05. Abbreviations: BMI, body mass index; SAD, sagittal abdominal diameter; LDL, low-density lipoprotein; HDL, high-density lipoprotein.</p
Correlation analysis of anthropometric and clinical parameters with serum RBP4, FABP4 and LCN2.
<p>Correlation analysis of anthropometric and clinical parameters with serum RBP4, FABP4 and LCN2.</p
Serum levels of FABP4, LCN2 and RBP4 in obese subjects with or without diabetes and in CVD patients.
<p>The CVD group had significantly higher level of serum RBP4 compared to any of the other groups. FABP4 values were significantly higher in obese, obese diabetic and CVD subjects compared to control and non-obese diabetic groups. LCN2 values were higher in CVD subjects than any of the others but this difference did not reach statistical significance (P = 0.46).</p
Establishment of principal components.
<p>Eigen vectors (factor loadings for standardized variables) for first two principal components.</p
Pearson correlations of CVD component 1 and BMI with anthropometric and biochemical parameters in CVD subjects.
<p>Pearson correlations of CVD component 1 and BMI with anthropometric and biochemical parameters in CVD subjects.</p
Prevalence of hypertriglyceridemia stratified according to age (adult criteria NCEP ATP III [<b>9</b>]).
<p>Prevalence of hypertriglyceridemia stratified according to age (adult criteria NCEP ATP III <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012159#pone.0012159-Expert1" target="_blank">[<b>9</b>]</a>).</p
Prevalence of low HDL-cholesterol stratified according to age (adult criteria NCEP ATP III [<b>9</b>]).
<p>Prevalence of low HDL-cholesterol stratified according to age (adult criteria NCEP ATP III <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012159#pone.0012159-Expert1" target="_blank">[<b>9</b>]</a>).</p
Prevalence of MetS in males and females according to age groups (adult criteria NCEP ATP III [<b>9</b>]).
<p>Prevalence of MetS in males and females according to age groups (adult criteria NCEP ATP III <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012159#pone.0012159-Expert1" target="_blank">[<b>9</b>]</a>).</p
Correlation between systolic blood pressure and ANG II (r = 0.17, p<0.05) (A); TNF-α (r = 0.2, p<0.001) (B) in the entire group studied.
<p>Correlation between systolic blood pressure and ANG II (r = 0.17, p<0.05) (A); TNF-α (r = 0.2, p<0.001) (B) in the entire group studied.</p