In the last two decades, the use of phthalates has been restricted worldwide due to their well-known toxicity. Nonetheless, phthalates are still widely used for their versatility, high plasticization effect, low cost, and lack of valuable alternatives. This study presents the fully bio-based and versatile glycerol trilevulinate plasticizer (GT) that was obtained by the valorization of glycerol and levulinic acid. The mild-conditions and solvent-free esterification used to synthesize GT was optimized by investigating the product by Fourier transform infrared and NMR spectroscopy. An increasing content of GT, from 10 to 40 parts by weight per hundred parts of resin (phr), was tested with poly(vinyl chloride), poly(3-hydroxybutyrate), poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(lactic acid), and poly(caprolactone), which typically present complicated processability and/or mechanical properties. GT produced a significant plasticization effect on both amorphous and semicrystalline polymers, reducing their glass-transition temperature and stiffness, as observed by differential scanning calorimetry measurements and tensile tests. Remarkably, GT also decreased both the melting temperature and crystallinity degree of semicrystalline polymers. Furthermore, GT underwent enzyme-mediated hydrolysis to its initial constituents, envisioning a promising prospective for environmental safety and upcycling. Furthermore, 50% inhibitory concentration (IC₅₀) tests, using mouse embryo fibroblasts, proved that GT is an unharmful alternative plasticizer, which makes it potentially applicable in the biomedical field.

Ovarian cancer (OC) grows and interacts constantly with a complex microenvironment, in which immune cells, fibroblasts, blood vessels, signal molecules and the extracellular matrix (ECM) coexist. This heterogeneous environment provides structural and biochemical support to the surrounding cells and undergoes constant and dynamic remodeling that actively promotes tumor initiation, progression, and metastasis. Despite the fact that traditional 2D cell culture systems have led to relevant medical advances in cancer research, 3D cell culture models could open new possibilities for the development of an in vitro tumor microenvironment more closely reproducing that observed in vivo. The implementation of materials science and technology into cancer research has enabled significant progress in the study of cancer progression and drug screening, through the development of polymeric scaffold-based 3D models closely recapitulating the physiopathological features of native tumor tissue. This article provides an overview of state-of-the-art in vitro tumor models with a particular focus on 3D OC cell culture in pre-clinical studies. The most representative OC models described in the literature are presented with a focus on hydrogel-based scaffolds, which guarantee soft tissue-like physical properties as well as a suitable 3D microenvironment for cell growth. Hydrogel-forming polymers of either natural or synthetic origin investigated in this context are described by highlighting their source of extraction, physical-chemical properties, and application for 3D ovarian cancer cell culture.

The use of Pt(IV) complexes as potential anticancer drugs is attractive, because they have higher stability and less side effects than Pt(II) compounds. Moreover, some Pt(IV) complexes can also be activated with light, opening an avenue to photochemotherapy. Our purpose is to widen the library of photoactivatable Pt(IV)-based prodrugs and here we report on the oxidation of the Pt(II) compound [PtCl(4′-phenyl-2,2′:6′,2′′-terpyridine)][CF₃SO₃] (1) with PhICl₂ or H₂O₂. The synthetic procedure avoids the formation of multiple species: the treatment with PhICl₂ produces the Pt(IV) complex with axial chlorides, [PtCl₃(4′-phenyl-2,2′:6′,2′′-terpyridine)][CF₃SO₃] (2), while H₂O₂ oxidation and post-synthesis carboxylation produce [Pt(OCOCH₃)₂Cl(4′-phenyl-2,2′:6′,2′′-terpyridine)][CF₃SO₃] (3), bearing acetates in the axial positions. 2 and 3 are stable in physiological-like buffers and in DMSO in the dark, but undergo photoreduction to 1 upon irradiation at 365 nm. Their stability toward reduction is a fundamental parameter to consider: cyclic voltammetry experiments show that the 2 electron reduction Pt(IV) → Pt(II) occurs at a more negative potential for 3, because of the greater stabilization provided by the acetate axial groups; noteworthily, 3 is stable for hours also in the presence of mM concentration of glutathione. The cytotoxicity of 2 and 3 toward A2780 and A2780cis cell lines reveals that 3 is the least toxic in the dark, but is able to produce cytotoxic effects far higher than cisplatin when irradiated. To shed light on the mechanistic aspects, the interaction with protein and DNA models has been explored through high-resolution mass spectrometry revealing that 2 and 3 behave as prodrugs, but are able to bind to biological targets only after irradiation.

Plasticizers are the most used polymer additives world-wide. Nowadays, conventional plasticizers (e.g. phthalates) do not meet the requirements in terms of renewability, biodegradability and cytotoxicity that have become necessary, especially if they are compounded with biopolymers. In this study, novel bioplasticizers are synthesized from levulinic acid via a protecting-group-free three-step process. After FT-IR and NMR characterization of the synthesized molecules, their plasticization effect has been tested with poly(3-hydroxybutyrate) (PHB) as a model semicrystalline biopolyester characterized by a narrow processing window, slow re-crystallization and high brittleness, which limit its processability and diffusion. The proposed bioplasticizers show remarkable miscibility with PHB and low leaching. The bioplasticizers also show a remarkable plasticization effect in terms of reducing the glass transition and melting temperatures (17 °C and 8 °C, respectively), which are comparable with the performance of the best commercially available green plasticizers. Furthermore, flexibility and crystallinity are positively affected, leading to an overall reduction in the typical brittleness of PHB. The observed effects result in an expansion of the temperature range in which PHB can be processed without thermal degradation. Moreover, the incorporation of the levulinic acid-based additives does not significantly affect the typical biodegradability and biocompatibility of PHB, showing their promising features as bioplasticizers for both environmental and biomedical applications.