In this study, the preparation of poly(vinyl alcohol) (PVA)/poly(lactic acid) (PLA) blends of different compositions, 100/0, 75/25, 50/50, 25/75, and 0/100, by mixing water solutions of the former and water dispersions of the latter polymer, is reported. Two distinct dispersions of PLA are prepared using a commercial‐grade polyester and two different surfactants, an anionic one and a neutral one. Films of PLA and of the corresponding blends are obtained by simply drying at 60 °C the water dispersions without or with the PVA. The films are characterized by infrared spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscope (SEM) analysis. This evidences an island‐like morphology, with the continuous phase consisting of a PVA rich phase at all compositions except 25/75, for which an inverted phase composition, with a continuous phase made mostly of PLA, is instead found. Voids caused by air bubbles trapped in the initial mixture are observed in particular in the formulations with the anionic surfactant. The trapped bubbles result in premature thermal degradation by thermogravimetric analysis (TGA) and mechanical failure during clamping. Films with the neutral stabilizer are tougher than the bare commercial PLA, with Young modulus and elongation at break depending on the combination of the composition and arrangement of blend phases.

Water-soluble amphiphilic random copolymers composed of tri(ethylene glycol) methacrylate (TEGMA) or poly(ethylene glycol) methyl ether methacrylate (PEGMA) and perfluorohexylethyl acrylate (FA) were synthesized by ARGET-ATRP, and their self-assembling and thermoresponsive behavior in water was studied by dynamic light scattering (DLS) and UV-vis spectroscopy. The copolymer ability to self-fold in single-chain nano-sized structures (unimer micelles) in aqueous solutions was exploited to encapsulate Combretastatin A-4 (CA-4), which is a very hydrophobic anticancer drug. The cloud point temperature (T_cp) was found to linearly decrease with increasing drug concentration in the drug/copolymer system. Moreover, while CA-4 was preferentially incorporated into the unimer micelles of TEGMA-ran-FA, the drug was found to induce multi-chain, submicro-sized aggregation of PEGMA-ran-FA. Anyway, the encapsulation efficiency was very high (≥81%) for both copolymers. The drug release was evaluated in PBS aqueous solutions both below and above T_cp for TEGMA-ran-FA copolymer and below T_cp, but at two different drug loadings, for PEGMA-ran-FA copolymer. In any case, the release kinetics presented similar profiles, characterized by linear trends up to ≈10–13 h and ≈7 h for TEGMA-ran-FA and PEGMA-ran-FA, respectively. Then, the release rate decreased, reaching a plateau. The release from TEGMA-ran-FA was moderately faster above T_cp than below T_cp, suggesting that copolymer thermoresponsiveness increased the release rate, which occurred anyway by diffusion below T_cp. Cytotoxicity tests were carried out on copolymer solutions in a wide concentration range (5–60 mg/mL) at 37 °C by using Balb/3T3 clone A31 cells. Interestingly, it was found that the concentration-dependent micro-sized aggregation of the amphiphilic random copolymers above T_cp caused a sort of “cellular asphyxiation” with a loss of cell viability clearly visible for TEGMA-ran-FA solutions (T_cp below 37 °C) with higher copolymer concentrations. On the other hand, cells in contact with the analogous PEGMA-ran-FA (T_cp above 37 °C) presented a very good viability (≥75%) with respect to the control at any given concentration.

Amphiphilic tetrafluorostyrene monomers (EFS8) carrying in the para position an oligoethylene glycol chain containing 8 oxyethylenic units on average were synthesized and used for preparation via activator regenerated by electron transfer atom transfer radical polymerization (ARGET-ATRP) of the corresponding amphiphilic homopolymers (pEFS8-x) with different degrees of polymerization (x = 26 and 46). Combining light transmittance and nano-differential scanning calorimetry (n-DSC) measurements revealed that pEFS8-x homopolymers displayed a lower critical solution temperature (LCST) thermoresponsive behavior in water solutions. Moreover, n-DSC measurements revealed the presence in heating scans of a broad endothermic peak ascribable to the dehydration process of the polymer single chains (unimers) and their collapse into aggregates. Consistently, dynamic light scattering (DLS) measurements showed below the LCST the presence of small nanostructures with a hydrodynamic diameter size D_h of 6–7 nm, which collapsed into concentration-dependent larger multichain aggregates (D_h = 300–3000 nm) above LCST. Interestingly, n-DSC data showed that the unimer-aggregate transition was reversible up to a specific temperature (T_rev) of each homopolymer, which in any case was higher than T_max. When heating above T_rev the transition was no longer reversible, causing the shift of T_onset and T_max at lower values, thus suggesting an increase in hydrophobicity of the polymer systems associated with a temperature-dependent dehydration process.