However, the CA-PEI micelles were ideally stable merely up to a definite concentration of CA (3:1). When the Selleck Opaganib molar fraction of CA was raised further, it also increased the hydrophilic segments, which raised the likelihood of interaction between the hydrophilic and hydrophobic segments and a decreased hydrophobicity of the core, consequently leading to an increased CMC. Figure 4 Critical micelle concentrations of CA-PEI micelles. High CMCs are

a key problem linked to micelle formulations given intravenously or diluted in blood. Low CMCs of CA-PEI micelles would thus offer some benefits, such as stability against dissociation and precipitation in blood due to dilution. In addition, embolism caused by the elevated amount of polymers used for the micelle formation could be avoided [21]. TEM micrographs of the CA-PEI micelles are shown in Figure 5. The micelles were observed to have a spherical shape and were uniform in size ranging from 150 to 200 nm. The bright areas perhaps encompassed

the hydrophobic part forming the micellar core, whereas the hydrophilic corona appeared to be darker because this region has a higher electron density than the core [22]. Figure 5 TEM images of CA-PEI micelles. CA-PEI 3:1 Small Molecule Compound Library (a, b), CA-PEI 1:1 (c, d), CA-PEI 4:1 (e, f), CA-PEI 1:2 (g, h), and CA-PEI 1:4 (i, j). Black scale bars represent 100 nm, and white scale bars represent 50 nm. The magnification of the images were × 160,000 (a, c), ×135,000 (e, h, j), ×105,000 (b, d, i), and × 87,000 (f, g). The formation of small, lustrous CA-PEI conjugates (1 to 2 mm) was an interesting finding; hence, they were subjected to XRD analysis (Figure 6). For CA alone, characteristic peaks were observed at 2θ = 12.0°, 13.1°, and 19.8° [23]. In contrast, the XRD patterns of the CA-PEI conjugates showed characteristic body-centered lattice peaks at 2θ = 7.6°, 15°, and 23.2°. The intensity of the peak at 2θ = 7.6° was maximum for all CA-PEI conjugates. The Thymidylate synthase sharp,

intense, and broad peaks of the CA-PEI conjugates indicated a crystalline nature of the conjugate. Figure 6 XRD patterns of CA and CA-PEI conjugates of five different molar feed ratios. The conjugates were then subjected to DSC analysis (Figure 7). When heated from 30°C to 250°C at 20°C/min, the CA crystals exhibited endothermic peaks due to fusion at 202°C [24], while a broad endothermic peak of a relatively lesser intensity was observed for PEI at 220°C. The DSC curve of the CA-PEI conjugate had two fusion peaks derived from CA and PEI at 220°C and 235°C, indicating the formation of conjugates. The intensity of the first peak was slightly higher than that of the second peak. Figure 7 DSC curves of CA, PEI, and CA-PEI conjugates with five different molar feed ratios. DLC and EE of micelles as calculated using Equations 1 and 2 are represented in Table 1. The in vitro release profile of the doxorubicin-loaded micelles in PBS solution (pH 7.4) was obtained, which is summarized in Figure 8.