Solubility of PTX and gPTX in different solvents.

<p>* <i>Solubility of H₂O was referred as described previously</i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107976#pone.0107976-Mandai1" target="_blank">[19]</a>.</p><p>** <i>CEP consists of Cremophor EL and ethanol in PBS (12∶12∶76 volume %)</i>.</p><p>Solubility of PTX and gPTX in different solvents.</p

Anticancer efficacy of different gPTX formulations with repeated administration in HT-29 cells tumor-bearing mice.

<p>gPTX-IL (open circle with line), gPTX-L (open triangle), gPTX-L with trastuzumab (open square), trastuzumab (closed square), CEP-IL (closed circle), CEP-L (closed triangle), or PBS (cross) was intravenously injected at day 0, 10, and 20. The dose of each administration was 150 mg/kg gPTX. A and B, Changes in tumor volume. C, Changes in body weight. D, Survival curves. Data are presented as the mean ± S.D. The changes of tumor volume and body weight in the mice administered with gPTX-L do not show S.D. after day 10. The <i>P</i> value shown compared with gPTX-IL and gPTX-L with trastuzumab treated group at day 43 (n = 4). *, <i>P</i><0.05.</p

Cytotoxicity of different gPTX formulations by the MTT assay.

<p>A, The IC₅₀ values after drug exposure for 72 h are shown. B, The IT₅₀ values at IC₁₀₀ are shown. The data are presented as the mean ± S.D. for three independent experiments. *, <i>P</i><0.05. **, <i>P</i><0.01. ***, <i>P</i><0.005. ****, <i>P</i><0.001. NSD, no significant difference.</p

Schematic illustration of remote loading with a solubility gradient.

<p>CEP-encapsulated liposomes (CEP-L) and gPTX dissolved in 40% EG were mixed and incubated. gPTX was encapsulated into liposomes under a solubility gradient.</p

Influence of the lipid composition and incubation time for drug encapsulation by the solubility gradient method.

<p>A, The encapsulation efficiency (EE) of gPTX-L with various lipid compositions was evaluated after 30 min of incubation for gPTX encapsulation. B, The drug retention of gPTX-L with different lipid compositions was evaluated in medium supplied with 10% FBS at 37°C. C, The efficiency of drug encapsulation under different durations of incubation was evaluated with a DPPC to Chol ratio of 3∶1.</p

Characterizations of gPTX.

<p>A, The hydrophobicity of PTX and gPTX was evaluated by reverse-phase HPLC using a C₁₈ column at a flow rate of 1 mL/min with 55% (v/v) methanol under an isocratic condition. B, The ability of 3 µM PTX (open circle) and gPTX (open triangle) to stabilize porcine tubulin polymerization was evaluated using a Tubulin Polymerization Assay Kit (Cytoskeleton). The fluorescent reporter was detected with excitation at 360 nm and emission at 420 nm. Each dot represents the mean ± S.D. (n = 3).</p