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  • br The thermal properties of


    The thermal properties of PTX, PM micelles, and micelles were evaluated by DSC. The melting curve of PTX showed an Mitomycin C peak at 219.7 °C and an exothermic peak at 242.9 °C (Fig. S2b). The melting curve of the PM micelles showed an endothermic peak at 217.1 °C, but an exothermic peak was not observed. In a previous study, the melting point peak of cabazitaxel disappeared in cabazitaxel-loaded micelles [40]. Our micelles did not show melting peaks. From these results, it is suggested that PTX was successfully loaded in micelles.
    In order to evaluate the interaction between PTX and the solu-bilizers (i.e., Soluplus® and TPGS), ATR-FT-IR analysis was performed. As shown in Fig. S4b, PTX has major absorbance bands of CeH 
    3.3. Dissolution and in vitro drug release study
    (%) than that of SD9 in all dissolution media. The differences in dis-solution (%) between SD4 and SD9 were 8–10% at 60 min. SD4 showed higher apparent solubility and dissolution (%) than SD9 (mono; TPGS) due to the synergistic effect of both polymers, PVP/VA S-630 and TPGS. 
    The dissolution (%) of PTX from SD formulations (SD4 and SD9) was in the order of DW > pH 6.8 > pH 1.2. Reason for SD formulations ex-hibiting pH-dependent dissolution profiles is unknown. However, the solubility of PTX is so low that there was no difference depending on the pH, and the solubility of the SD preparation was significantly im-proved, exhibiting pH-dependent dissolution pattern. The dissolution of SD4 was significantly higher than that of SD9 at 60 min (paired t-test;
    method, showed high dissolution (%) in SIF without pancreatic en-zymes (pH 6.8). However, this SD formulation showed low dissolution
    (%) before 30 min [27]. SD formulations (containing PVP K30, SDS, and Tween® 80) significantly increased the dissolution (%) of PTX (~80%) in simulated gastric fluid. However, the early dissolution (%) of this SD (before 20 min) was also very low [28]. The above SD formulations were composed of SDS and Tween® 80, commonly used to improve the solubility of most drugs [41–43]. In addition, there is no physico-chemical comparison with PM (physical mixture). Although the dis-solution (%) of PTX was high, the mechanism was not suggested. From the results of ATR-FT-IR spectroscopy, we suggested that the dissolution
    (%) of PTX increased by intermolecular interactions between PTX and TPGS.
    pattern compared to that in pH-shifting media (Fig. 4b). The release pattern of PTX showed higher than that of micelles in all medium. After 48 h, the drug release (%) showed approximately 80% (PTX) and 60% (micelles) in all medium. Moreover, PTX showed almost similar drug release in Tween® 80 and SLS surfactants contained medium. In pre-vious studies, the release patterns of PTX or PTX-micelles showed si-milar [25,29,30].
    3.4. Stability study
    In order to evaluate the stability, SD4 and SD9 formulations were
    kept at room temperature (25 ± 5 .0 °C) and accelerated conditions
    was maintained at all time periods and storage conditions (Fig. 5a,b).
    The drug contents of SD formulations (SD4 and SD9) were very stable,
    95.6 ± 3.1% (40 °C, 3 months), respectively. In a previous study, as the amount of Aerosil® 200 increased, the dissolution (%) and stability of itraconazole with TPGS improved in SD formulations [44]. A coenzyme Q10 (CoQ10) SD formulation with Aerosil® 200 maintained solubility for 30 days; however, without Aerosil® 200, this SD formulation showed decreased solubility after 1 day [45]. Since Aerosil® 200 has a large specific surface area, it inhibited the recrystallization of the drug and improved its stability. By comparison, we believed that our formula-tions would be stable.
    3.5. Cytotoxicity study
    In RAW 264.7 cells, the samples were not toxic at all PTX con-centrations; over 80% of the cells survived. Thus, SD4, SD9, and mi-celles (M2) appeared safe for normal cells. In BT-474 cells, the micelles (M2) showed higher cytotoxicity than the other formulations did. The cytotoxicity of the PTX formulations was 3.4-fold (M2), 3.0-fold (SD4), and 2.8 fold (SD9) higher than that of PTX at 20 μg/mL. In MCF-7 cells, the micelles (M2) also showed higher cytotoxicity than the other for-mulations did. The cytotoxicity of the PTX formulations was 4.4-fold (M2), 4.0-fold (SD4), and 4.1 fold (SD9) higher than that of PTX at 20 μg/mL. In SK-BR-3 cells, the micelles (M2) also showed higher cy-totoxicity than the other formulations did. The cytotoxicity of the PTX formulations was 6.7-fold (M2), 5.6-fold (SD4), and 5.0-fold (SD9) higher compared to that of PTX at 20 μg/mL. Blank SD formulations (SD4 and SD9) and micelles were not cytotoxic to the cell lines in Fig. S5.