Unimolecular micelles based on selectively hydrophobized hyperbranched polyglycidols, hHbPGLs, in the macromolecule's interior are used for the enhancement of hydrophobic drug solubility in aqueous media and as a major component of hydrophobized hydrogel-based drug delivery systems. In this article, we have investigated the thermosensitive behavior of amphiphilic hyperbranched polyglycidol obtained by the hydrophobization of the core with phenyl moieties, i.e., by modification of monohydroxyls of linear constitutional repeating units (L 13 and L 14 ) of hyperbranched polyglycidol, HbPGL, incorporating benzoyl ester or phenylurethane groups, with terminal 1,2-diols in the corona remaining intact. A turbidimetric study revealed that hHbPGLs equipped with benzoyl ester (BE) groups with the degree of substitution of linear units ranging from 42 to 56 mol % and phenylurethane moieties (PC) in the range from 32 to 55 mol % in water showed lower critical solution temperature (LCST) behavior. The critical point was, however, observed at a very low concentration, approximately 3.75 mg/mL, for both HbPGL derivatives. Thus, an increase of T cp based on the concentration was observed in the broad concentration range. In addition, a significant difference in T cp reaching up to 40 °C for aqueous solutions of PC and BE derivatives of HbPGL of a comparable degree of substitution of monohydroxylated groups (DS ∼ 50%) at a concentration equal to 150 mg/mL was detected. Raman spectra recorded for polymer-rich phases obtained upon phase separation for PC and BE derivatives revealed lower hydration of the PC derivative, indicating its higher tendency to intermolecular interactions and thus lower T cp . Computational modeling methods, such as density functional theory, DFT, and molecular dynamics, MD, showed that in the case of the BE derivative, unlike the PC derivative, the phenyl rings were effectively surrounded by hydrated polyether branches, which hindered the aggregation of phenyl rings. Both Raman spectroscopy and computational investigations revealed the difference in the hydration state of the aromatic group depending on the used covalent linkage. Moreover, BE and PC derivatives displayed an asymmetric phase diagram, i.e., the dependence of T cp on the polymer concentration. In general, for polymers at very broad concentrations ranging from 15 to 275 mg/ mL BE and PC derivatives, respectively, an increase of T cp with the increase of the polymer concentration was observed. Only in a very low concentration range from 0.12 to 3.75 mg/mL did polymers exhibit a decrease of T cp with the increase of the polymer concentration. It results from the screening of the hydrophobic groups within highly water-swollen polyether branches upon the increase of the polymer concentration. The phase separation of higher-concentrated solutions required a further increase in temperature, resulting in partial dehydration of the polyether branches, which increased the hydrophobicity of the macromolecules, and the separation of the polymer from the ...
