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  • br Characterization of micelles br Micelles were successfully prepared

    2022-09-16


    3.2. Characterization of micelles
    Micelles were successfully prepared with Soluplus® and TPGS, as shown in Table S1. The ratio of Soluplus® to TPGS (4:1) was optimized via preliminary tests (data not shown). We selected methylene chloride as the organic solvent, which could easily be removed, and then used the film hydration method. This prevented toxicity due to residual or-ganic solvent.
    The PTX concentration in the micelle suspensions was problematic because the low concentrations of PTX in the animal study could not be detected by HPLC methods. To improve the drug loading, the weight of PTX (15 mg) was fixed and the weight of polymer was decreased from M1 to M5. Among the five formulations, only M2 could be filtered. Specifically, M1 could not be filtered due to the high viscosity of the large concentration of polymers, and M3-M5 could not be filtered be-cause a lot of the PTX was not loaded in micelles. The optimized for-mulation (M2) was a milky solution with an average particle size of 61.2 ± 2.4 nm and a narrow polydispersity index (PDI) of 0.07 ± 0.01 using a Zeta-sizer (Nano-90). The spherical morphology of the Poly(I:C) micelles was confirmed, and the particle size was shown to be 57.9 ± 10.2 nm (Fig. 2B). The drug loading (%) and encapsulation efficiency (%) were 10.4 ± 0.35% and 98.7 ± 3.48%, respectively. The M2 formulation has a smaller particle size and an increased en-capsulation efficiency (%) compared with those of the previous studies [25,29].
    The thermal properties of PTX, PM micelles, and micelles were evaluated by DSC. The melting curve of PTX showed an Poly(I: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