Eugenol is a phenolic monoterpenoid, obtained mainly from clove oil and lignin, with a peculiar chemical structure containing an allyl group and a phenol group, which can be easily subjected to chemical modification. The phenol group also endows eugenol with antimicrobial activity and the ability to scavenge reactive oxygen species. Here, we present eugenol as a building block for the obtainment of antimicrobial and antioxidant bio-based polymers. So far, the approaches followed to obtain EU-based polymers involved phenol group functionalisation with polymerisable moieties, which inevitably implied the loss of the antioxidant activity of eugenol. In contrast, herein, an efficacious and low environmental impact synthetic strategy was set up to obtain an eugenol-methacrylate (EUMA) monomer bearing a free phenol group. EUMA was copolymerised with 2-hydroxyethyl methacrylate (HEMA) at different volume percentages (10%, 30% and 50%). The EUMA homopolymer was also synthesised. The obtained amorphous polymers were as thermally stable as pHEMA but more flexible (lower T_g) and hydrophobic (less swellable in water) than pHEMA. The rheological tests evidenced that all of the EU-containing polymers have good inherent elastic properties, which were retained also at high deformation frequencies (up to 80 Hz). Thanks to the presence of phenol groups in the side chain of the polymers, the pHEMA-EU copolymers showed significant radical scavenging activity and also antimicrobial activity towards a strain of Staphylococcus epidermidis. Overall, the synthesised eugenol-methacrylate monomer has the potential to be copolymerised with a wide number of different acrylate or vinyl monomers, thus allowing one to prepare a library of polymers with the desired physical and biological properties. The cutting-edge antioxidant and antimicrobial properties shown by the prepared copolymers open an interesting perspective towards the use of these materials in different application fields, including the food sector and biomedical field.

Volumetric Additive Manufacturing (VAM) represents a revolutionary advancement in the field of Additive Manufacturing, as it allows for the creation of objects in a single, cohesive process, rather than in a layer-by-layer approach. This innovative technique offers unparalleled design freedom and significantly reduces printing times. A current limitation of VAM is the availability of suitable resins with the required photoreactive chemistry and from sustainable sources. To support the application of this technology, we have developed a sustainable resin based on polyglycerol, a bioderived (e.g., vegetable origin), colourless, and easily functionisable oligomer produced from glycerol. To transform polyglycerol-6 into an acrylate photo-printable resin we adopted a simple, one-step, and scalable synthesis route. Polyglycerol-6-acrylate fulfils all the necessary criteria for volumetric printing (transparency, photo-reactivity, viscosity) and was successfully used to print a variety of models with intricate geometries and good resolution. The waste resin was found to be reusable with minimal performance issues, improving resin utilisation and minimising waste material. Furthermore, by incorporating dopants such as poly(glycerol) adipate acrylate (PGA-A) and 10,12-pentacosadyinoic acid (PCDA), we demonstrated the ability to print objects with a diverse range of functionalities, including temperature sensing probes and a polyester excipient, highlighting the potential applications of these new resins.

Polymersomes are an exciting modality for drug delivery due to their structural similarity to biological cells and their ability to encapsulate both hydrophilic and hydrophobic drugs. In this regard, the current work aimed to develop multifunctional polymersomes, integrating dye (with hydrophobic Nile red and hydrophilic sulfo-cyanine5-NHS ester as model drugs) encapsulation, stimulus responsiveness, and surface-ligand modifications. Polymersomes constituting poly(N-2-hydroxypropylmethacrylamide)-b-poly(N-(2-(methylthio)ethyl)acrylamide) (PHPMAm-b-PMTEAM) are prepared by aqueous dispersion RAFT-mediated polymerization-induced self-assembly (PISA). The hydrophilic block lengths have an effect on the obtained morphologies, with short chain P(HPMAm)₁₆ affording spheres and long chain P(HPMAm)₄₃ yielding vesicles. This further induces different responses to H₂O₂, with spheres fragmenting and vesicles aggregating. Folic acid (FA) is successfully conjugated to the P(HPMAm)₄₃, which self-assembles into FA-functionalized P(HPMAm)₄₃-b-P(MTEAM)₃₀₀ polymersomes. The FA-functionalized P(HPMAm)₄₃-b-P(MTEAM)₃₀₀ polymersomes entrap both hydrophobic Nile red (NR) and hydrophilic Cy5 dye. The NR-loaded FA-linked polymersomes exhibit a controlled release of the encapsulated NR dye when exposed to 10 mM H₂O₂. All the polymersomes formed are stable in human plasma and well-tolerated in MCF-7 breast cancer cells. These preliminary results demonstrate that, with simple and scalable chemistry, PISA offers access to different shapes and opens up the possibility of the one-pot synthesis of multicompartmental and responsive polymersomes.

Despite the success of polyethylene glycol-based (PEGylated) polyesters in the drug delivery and biomedical fields, concerns have arisen regarding PEG's immunogenicity and limited biodegradability. In addition, inherent limitations, including limited chemical handles as well as highly hydrophobic nature, can restrict their effectiveness in physiological conditions of the polyester counterpart. To address these matters, an increasing amount of research has been focused towards identifying alternatives to PEG. One promising strategy involves the use of bio-derived polyols, such as glycerol. In particular, glycerol is a hydrophilic, non-toxic, untapped waste resource and as other polyols, can be incorporated into polyesters via enzymatic catalysis routes. In the present study, a systematic screening is conducted focusing on the incorporation of 1,6-hexanediol (Hex) (hydrophobic diol) into both poly(glycerol adipate) (PGA) and poly(diglycerol adipate) (PDGA) at different (di)glycerol:hex ratios (30:70; 50:50 and 70:30 mol/mol) and its effect on purification upon NPs formation. By varying the amphiphilicity of the backbone, we demonstrated that minor adjustments influence the NPs formation, NPs stability, drug encapsulation, and degradation of these polymers, despite the high chemical similarity. Moreover, the best performing materials have shown good biocompatibility in both in vitro and in vivo (whole organism) tests. As preliminary result, the sample containing diglycerol and Hex in a 70:30 ratio, named as PDGA-Hex 30%, has shown to be the most promising candidate in this small library analysed. It demonstrated comparable stability to the glycerol-based samples in various media but exhibited superior encapsulation efficiency of a model hydrophobic dye. This in-depth investigation provides new insights into the design and modification of biodegradable (di)glycerol-based polyesters, potentially paving the way for more effective and sustainable PEG-free drug delivery nano-systems in the pharmaceutical and biomedical fields.

Polymers are among the most studied materials as drug carriers, due to their tunable chemical structure and ability to self-assemble to give different types of nanostructures. In this study, chitosan (CS) nanoparticles (NPs) were investigated as carriers for the anticancer drug sodium usnate (NaU) for the treatment of osteosarcoma (OS), which is the most prevalent primary malignant bone sarcoma in pediatric and adolescent patients. CS nano-assembling was induced by electrostatic interactions with the drug and the anionic cross-linker tripolyphosphate, thus obtaining stable nanosystems and a high drug encapsulation efficiency. Importantly, a reduction in NaU hepatotoxicity when encapsulated in CS NPs compared to free NaU was evidenced, suggesting that CS may have a protective role against liver damage. Unfortunately, NaU encapsulation also reduced drug toxicity versus osteosarcoma 143B cells compared to free NaU. Nevertheless, NaU-loaded CS NPs (0.312 mg/mL) were found to decrease 143B cells viability after 48 h and 72 h treatment without being hepatotoxic. Interestingly, this system also stimulated in 143B cells Maspin production, an agent known for its tumor suppressor properties. Relevant synergistic activity between CS and NaU in promoting Maspin stimulation was found. That suggests the potential of the systems to reduce invasiveness of OS cancer.