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• Overproduction of glycerol and CO 2 arises the need to convert them into valuable new molecules. • Bio-based nanoparticles from modular copolymers have been synthetized converting glycerol and CO 2. • RAFT is used for the first time on glycerol-based monomers to provide a controlled polymer structure. • Polymer nanoparticles with up to 75% bio-based content by weight were produced. • These biodegradable nanoparticles have been tested in the controlled drug delivery. The biodiesel industry has grown rapidly in the last years, leading to the production of 88 000 tons of waste glycerol in 2018. Glycerol is a bio-derived molecule already exploited in pharmaceutical and cosmetic industries for its beneficial emollient and antimicrobial properties, safety and low cost. However, since its production is increasing year by year, many efforts are being done to find new ways to exploit it and to produce new valuable bio-based molecules. In particular, glycerol carbonate is a versatile molecule that can be produced from glycerol and another waste product, CO 2. Despite its potentialities in further functionalization, harsh reaction conditions are often required for the synthesis of glycerol carbonate and its exploitation is often challenging. Therefore, an industrially scalable reaction to convert glycerol into high added-value compounds is urgently needed. Here, the aim is to demonstrate a feasible conversion of glycerol to glycerol carbonate-based vinyl monomers that can be conveniently incorporated in amphiphilic block copolymers by reversible addition-fragmentation chain transfer (RAFT) polymerization. These block copolymers can be self-assembled in water to obtain nanoparticles with a bio-based content as high as 70% w/w. Since both glycerol and glycerol carbonate are approved by the Food and Drug Administration (FDA) and considered as safe, the possibility of exploiting these bio-based nanoparticles for the controlled drug release was explored. [ABSTRACT FROM AUTHOR]

[Display omitted] • Betaine-based copolymers are synthetized via RAFT polymerization. • RAFT polymerization enables the synthesis of tunable thermoresponsive nanoparticles. • Iron oxide nanoclusters are used to activate magnetic hyperthermia in nanoparticles. • Nanocluster-related hyperthermia ensures an on-demand drug release from nanocarriers. The smart combination of controlled drug delivery and magnetic hyperthermia represents a promising approach for potentiating tumor therapeutic treatments, with minimal adverse effects. Indeed, thermoresponsive nanoparticles enable an on-demand drug release according to their thermal activation, and the polymeric nanosystems characterized by an Upper Critical Solution Temperature (UCST) are leading candidates for hyperthermia-based strategies. Secondly, heating processes promoted by superparamagnetic nanostructures might enable targeted hyperthermic effects, without interfering on healthy cells. In this work, we combined the advantages of the UCST-type nanoparticles and superparamagnetic iron-based nanoclusters to design innovative nanocomposites for tunable drug release, activated by magnetic hyperthermia. The thermoresponsive nanoparticles were obtained via self-assembling of an amphiphilic zwitterionic block copolymer, and the nanoclusters were encapsulated into the polymeric scaffolds via flash nanoprecipitation. The organic and inorganic materials were characterized in terms of composition, size and physicochemical properties, highlighting the potential of the reversible addition–fragmentation chain transfer (RAFT) emulsion polymerization in tuning the copolymer composition and the cloud point of the nanoparticles (investigated range: 30–43 °C). We chose 43 °C as representative temperature of hyperthermia treatment and we validated our nanocomposites as delivery system for paclitaxel, a chemotherapeutic agent, under alternate magnetic field. The combined effect of magnetic hyperthermia and the polymer thermoresponsive behavior ensured an on-demand drug release when the target temperature was achieved, providing an almost complete drug release in the first two hours. Alternatively, without a magnetically-mediated heating, the nanocomposites retained the payload. This could pave the way for the definition of advanced hyperthermia-mediated therapeutic treatments. [ABSTRACT FROM AUTHOR]

[Display omitted] • Use of lignin oligomers in the synthesis of a bio-based pre-polymer via ring-opening of caprolactone. • Synthesis of a lignin-based polyurethane (LBPU) via urethane bonding of the pre-polymer. • Tuning the reaction parameters to modulate properties and degradation of the proposed LBPUs. Bio-based and degradable materials were proposed to challenge the major problem of plastic disposal in the environment. In this context, polyurethane production was re-evaluated, encouraging the search for replacing both petroleum components and highly toxic species. A novel synthesis route is explored in this work, aimed to produce degradable lignin-based polyurethanes. Oligomers from steam-exploded lignin were extracted and used with ε-caprolactone (ε-CL) to generate a fully bio-based pre-polymer (oligo- grafted -poly(ε-CL)), exploiting ring-opening polymerization. We have demonstrated that tuning the main reaction parameters, such as ε-CL:oligomer and catalyst:ε-CL mass ratios, and reaction time, it is possible to obtain different pre-polymers enabling the synthesis of bio-based polyurethanes with variable physicochemical properties. In particular, the oligomeric content modulates the thermal and mechanical properties of the polymer (melting point range: 54–62 °C; Young modulus range: 3–7 kPa) and enhances the degradability (up to 13 % wt, in acid environment), highlighting the potential of the material for possible applications. [ABSTRACT FROM AUTHOR]

Abstract: Thin film deposition is a process complicated by chemical and physical phenomena that take place on different time and length scales. Its correct description requires the development of multiscale models. Here we present the multiscale approach we developed to study the epitaxial chemical vapour deposition (CVD) and etching processes. The model is designed to describe the atomic scale with quantum chemistry, the morphology evolution at the mesoscale with a Kinetic Monte Carlo (KMC) model utilizing parameters either taken from the literature or computed with the atomic scale model, and the fluid dynamic and local composition in the reactor through the solution of mass, energy and momentum conservation equations with the finite element method. The multiscale approach was used to investigate the gas-phase chemistry active during the MOCVD of II–VI semiconductors, the morphology evolution during the epitaxial deposition of Si, and the fluid dynamic and gas-phase composition in a plasma-etching reactor. [Copyright &y& Elsevier]

Environmental concerns are pushing towards more sustainable materials such as degradable or bio-based polymers. 2-methylen-1,3-dioxepane (MDO) is a cyclic ketene acetal monomer that when reacts by radical ring opening polymerization can introduce degradable ester groups in the polymer backbone, but it is generally challenging to incorporate it uniformly with other industrially relevant vinylic monomers such as styrenics, methacrylics, acrylics and vinylics. In this work, we explore the use of butyl crotonate as termonomer to enhance the incorporation of MDO into common industrial monomers taking advantage of the particular reactivities of MDO and crotonate. Styrene is found not suitable for terpolymerization, as it just homopolymerized. With methyl methacrylate, the incorporation of MDO is substantially enhanced due to the presence of BCr, but the terpolymer is not homogeneous, and MDO is primarily incorporated in the closed form, which only partially enhanced the degradability. In the terpolymerization with ethyl acrylate high MDO incorporation is achieved (up to 80 %) and most of it is incorporated in to the open formed (80 %). Therefore, the obtained terpolymer shows complete degradation in 28 days. Last, the terpolymerization of vinyl acetate is the most successful, as almost total conversion of all monomers is achieved in short times, including (100 % conversion of MDO). Furthermore, the obtained terpolymers are highly homogeneous and degraded completely in few hours. The addition of crotonate monomer in formulations where MDO or other cyclic ketene acetal could bring new insights as it is shown that not only the incorporation of cyclic ketene acetals is enhanced but also that it favors the incorporation into the open form, which substantially enhanced the degradability of common polymers produced by radical polymerization. [Display omitted] • A crotonate termonomer enhances the incorporation of MDO into industrial monomers due to its particular reactivities with MDO. • In the case of vinyl acetate and ethyl acrylate the MDO is incorporated primarily into the open form. • The crotonate as termonomer substantially enhances the degradability of polymers produced by radical polymerization with MDO. [ABSTRACT FROM AUTHOR]

Biodegradable polymeric nanoparticles (NPs) are attracting increasing attention as carriers for drug delivery. However, one of the main factors limiting their transition to the market is their premature degradation and release of the payload during the storage. Therefore, for increasing the formulation shelf-life, the removal of water is of paramount importance. In this work, we synthesized both polyethylene glycol (PEG)-stabilized and zwitterionic NPs via Reversible Addition Fragmentation Chain Transfer (RAFT) Polymerization. We demonstrated that lyophilization leads the PEGylated NPs to irreversible aggregation, while the stability of the zwitterionic NPs was preserved only using a cryoprotectant. Therefore, we developed an alternative method for the NP concentration, based on the dialysis against a concentrated PEG solution. This method was optimized in terms of concentration factor (Fc), the ratio between the final and initial NP concentration, by acting on the PEG concentration in the dialysis medium, on its volume and on the initial NP concentration. With this approach, Fc up to 40 can be achieved in less than 10 h, preserving the possibility of redispersing the NPs to their original particle size distribution. Therefore, the dialysis proposed herein is a valuable alternative to lyophilization for the concentration of polymer NPs preserving their stability. [ABSTRACT FROM AUTHOR]

Cell-selective drug release in the central nervous system (CNS) holds great promise for the treatment of many CNS disorders but it is still challenging. We previously demonstrated that polymeric nanoparticles (NPs) injected intra-parenchyma in the CNS can be internalized specifically in microglia/macrophages surrounding the injection site. Here, we explored NPs administration in the cerebrospinal fluid (CSF) to achieve a wider spreading and increased cell targeting throughout the CNS; we generated new NPs variants and studied the effect of modifying size and surface charge on NPs biodistribution and cellular uptake. Intra-cerebroventricular administration resulted in prevalent localization of the NPs in proximity to stem-cell niches, such as around the lateral ventricles, the subventricular zone and the rostral migratory stream. NPs internalization occurred preferentially in brain myeloid cells/microglia. We demonstrated that brain biodistribution and extent of internalization in microglia are influenced by NPs dimensions and can be improved by applying a transient disruption of the blood-brain barrier with mannitol, leading to NPs internalization in up to 25% of brain myeloid/microglia cells. A fraction of the targeted cells was positive for markers of proliferation or stained positive for stemness/progenitor-cell markers such as Nestin, c-kit, or NG2. Interestingly, through these newly formulated NPs we obtained controlled and selective release of drugs otherwise difficult to formulate (such as busulfan and etoposide) to the target cells, preventing unwanted side effects and the toxicity obtained by direct brain delivery of the not encapsulated drugs. Overall, these data provide proof of concept of the applicability of these novel NP-based drug formulations for achieving internalization not only in mature microglia but also possibly in more immature myeloid cells in the brain and pave the way for brain-restricted microglia-targeted drug delivery regimens. Image 1 [ABSTRACT FROM AUTHOR]

[Display omitted] • A promising recycling process for PET is glycolysis, leading to difficult-to-purify BHET. • We investigated BHET transesterification to DMT, easier to purify and repolymerize. • A predictive kinetic model was developed and validated in a wide range of conditions. • Conclusions on the influence of catalyst, methanol excess and dry content are drawn. The accumulation of plastic waste in the environment is making recycling a compelling issue, particularly for polyethylene terephthalate (PET), used in products with a short shelf-life. An appealing route to chemical recycling of PET is glycolysis, leading to bis(2-hydroxyethyl) terephthalate (BHET). Its subsequent transesterification with methanol to dimethyl terephthalate (DMT) is crucial for the recovery of polymer-grade monomers. To favor the industrial applicability of this process, this work investigates the influence of three main parameters, i.e. the methanol to ethylene glycol molar ratio, the solvent to oligomers molar ratio and the mass fraction of the catalyst, on the transesterification of BHET to DMT. A kinetic model has been proposed, and the reaction rates evaluated by comparison with the experimental data. The model was used to predict the performances of the process in a wide range of operating conditions, in order to establish the optimal ones for high yield to DMT. [ABSTRACT FROM AUTHOR]

This review discusses the advances and main applications of thermo-responsive polymers used to impart a dynamic behavior to surfaces in different size range, from nanometers to millimetres. [Display omitted] The great versatility and controllable properties that characterize polymeric materials allowed their spreading to many different areas. In the last years, this outstanding adaptability was even amplified by the introduction of smart polymers, i.e. materials able to sharply and often reversibly change their physico-chemical properties in response to external stimuli. In particular, the possibility of applying thermal stimuli in a controlled and simple way, coupled with the natural occurrence of thermal gradients, made thermo-responsive polymers particularly appealing, as they allowed to conceive applications that were not even imaginable for traditional materials. In this review we discuss the great potentialities of thermo-responsive polymers when used to functionalize a target surface or interface. The discussion will cover significant areas of interest where this class of materials has been employed, including cell culture, chromatography, colloidal stabilization and enhanced oil recovery. Many examples from the literature are reported in order to present the state of the art, the main advantages of this technology over conventional materials and the expected future developments. Moreover, some successful examples highlighting the innovative functionalities achievable by these active surfaces are presented. [ABSTRACT FROM AUTHOR]

The reversible addition-fragmentation chain transfer (RAFT) copolymerization of non-ionized acrylic acid with acrylamide in dimethyl sulfoxide is investigated and compared with the conventional free radical process carried out at the same conditions. The effect of the living nature of the RAFT process on overall polymerization rate and on copolymer composition is studied by in situ 1 H NMR. The same values of reactivity ratios (r AA = 1.55 ± 0.02 and r Am = 0.75 ± 0.02) are estimated for both the processes, living and non-living. The copolymers prepared by RAFT polymerization exhibit well-controlled composition, with narrow distribution. This approach can be applied to the synthesis of copolymer standards at specific composition for direct calibration of size-exclusion chromatography. [ABSTRACT FROM AUTHOR]

Many efforts have been performed in order to understand the role of recruited macrophages in the progression of spinal cord injury (SCI). Different studies revealed a pleiotropic effect played by these cells associated to distinct phenotypes (M1 and M2), showing a predictable spatial and temporal distribution in the injured site after SCI. Differently, the role of activated microglia in injury progression has been poorly investigated, mainly because of the challenges to target and selectively modulate them in situ . A delivery nanovector tool (poly-ε-caprolactone-based nanoparticles) able to selectively treat/target microglia has been developed and used here to clarify the temporal and spatial involvement of the pro-inflammatory response associated to microglial cells in SCI. We show that a treatment with nanoparticles loaded with minocycline, the latter a well-known anti-inflammatory drug, when administered acutely in a SCI mouse model is able to efficiently modulate the resident microglial cells reducing the pro-inflammatory response, maintaining a pro-regenerative milieu and ameliorating the behavioral outcome up to 63 days post injury. Furthermore, by using this selective delivery tool we demonstrate a mechanistic link between early microglia activation and M1 macrophages recruitment to the injured site via CCL2 chemokine, revealing a detrimental contribution of pro-inflammatory macrophages to injury progression after SCI. [ABSTRACT FROM AUTHOR]

[Display omitted] • The huge production volume of plastics imposes a sustainable management of the waste. • PET methanolysis to monomers is applied in industries but at extreme conditions. • We explore different catalysts and cosolvents for PET methanolysis at mild conditions. • Based on quantitative comparisons, we promote a conscious selection of the catalyst. • The process is applied on bottle flakes and textile fibers mixed in cotton and PET. Plastic disposal is becoming a threat to our environment because of the severe lack of technologies producing high-quality polymers from scraps at a competitive cost compared to the virgin versions. Regarding polyethylene terephthalate (PET), different recycling technologies have been proposed, but they have several disadvantages in terms of cost, process flexibility, and safety. This work systematically investigates the efficiency of different catalytic systems in the methanolysis of PET, operated at mild temperature. High-performance liquid chromatography was adopted to assess the depolymerization efficacy and the product distribution, allowing a quantitative comparison between the different catalytic systems. Potassium carbonate and dichloromethane proved to be the best performing catalyst/cosolvent pair, leading to almost complete depolymerization of PET from bottle flakes and high yield to dimethyl terephthalate. On the other side, when treating PET/cotton fabrics, the hydrolysis catalyzed by hydroxyl groups in the cotton hampered the complete PET depolymerization, leaving room for further research. [ABSTRACT FROM AUTHOR]

Abstract: A delivery system based on polymer nanoparticles (NPs) is developed and tested in relevant biological conditions for breast cancer treatment. ɛ-Caprolactone (CL) and polyethylene glycol (PEG) copolymers have been used for the one pot synthesis of surfactant free PEGylated NPs which are monodispersed, stable in physiological conditions and have size in the range 90–250nm. The degradation behavior of these NPs has been investigated in cell medium and a relation between degradation time and molecular weight of the starting CL-based material has been established. This allows producing NPs with controlled degradation kinetics. Finally, selected NPs have been tested in 4T1 breast cancer cells to check their toxicity and to investigate the uptake process, in order to validate their use as targeted vectors for breast cancer treatment. [Copyright &y& Elsevier]

Abstract: Amino acid thioesters used as substrates for a chemo-enzymatic dynamic kinetic resolution (DKR) must be designed with a high enough acidity to be rapidly racemized in the presence of a suitable base. Kinetic data obtained from experimental proton exchange rates are correlated with thermodynamic data for the proton abstraction based on the density functional theory (DFT) calculations. The good correlation obtained allows to evaluate the contribution of different functional groups to the carbon acidity and to define bases able to perform the required racemization. [Copyright &y& Elsevier]

This review provides the guidelines to efficiently produce a polymeric formulation able to guarantee a sustained release of positively charged antiseptics for the long-term sterility in the treatment of health care-associated infections. [Display omitted] • Health care-associated infections are strongly impacting our society. • The release of cationic antiseptics is a solution against antibiotic-resistant bacteria. • We review polymeric systems highlighting crucial aspects for a controlled antiseptic release. • Monomer hydrophilicity and polymer molecular weight allow modulating the release rate. • Carboxyl functionalities lower the initial burst of antiseptic from the formulation. Nowadays, the treatment of health care-associated infections represents a serious issue, due to the increasing number of bacterial strains resistant to traditional antibiotics. The use of antiseptics like quaternary ammonium salts and biguanides is a viable alternative to face these life-threatening infections. However, their inherent toxicity as well as the necessity of providing a sustained release to avoid the formation of pathogen biofilms are compelling obstacles towards their assessment in the hospitals. Within this framework, the role of polymeric drug delivery systems is fundamental to overcome the aforementioned problems. Biocompatibility, biodegradability and excipient-drug interactions are crucial properties determining the efficacy of the formulation. In this work, we provide an in-depth analysis of the polymer drug delivery systems that have been developed or are under development for the sustained release of positively charged antiseptics, highlighting the crucial characteristics that allowed to achieve the most relevant therapeutic effects. We reported and compared natural occurring polymers and synthetic carriers to show their pros and cons and applicability in the treatment of health care-associated infections. Then, the discussion is focused on a particularly relevant class of materials adopted for the scope, represented by polyesters, which gave rise, due to their biodegradability, to the field of resorbable drug delivery devices. Finally, a specific analysis on the effect of the polymer functionalization over the formulation performances for the different types of polymeric carriers is presented. [ABSTRACT FROM AUTHOR]

• OHC encapsulation can be highly improved exploiting the electrostatic interaction. • OHC release is tuned varying the polymer end group, molecular weight, and composition. • Carboxy end groups enhance the degradation of the polymer and thus the release of the drug. • Acid end groups provide an efficient encapsulation and a sustained release of OHC. • Therapeutic concentration providing antimicrobial activity and human cell viability. Nosocomial infections remain a serious threat even for patients of highly industrialized countries. These infections occur on surgical sites and wounds, on catheter entry sites, tubes and other indwelling devices. Medical devices providing local antiseptic action over an extended time period represent an opportunity to prevent such infections. One way to achieve this goal is the encapsulation of active molecules into bioresorbable polymer microparticles, which can locally release the compound of interest along a tunable time span depending on the polymer characteristic. In this work, spray drying is used to encapsulate the broad band antiseptic octenidine hydrochloride into a set of poly(d , l -lactide) (PDLLA) and poly(d , l -lactide-co-glycolide) (PLGA) carrier materials with different molecular weights and chain end-groups, forming redispersable powders. It is demonstrated that the carrier materials bearing acid end-groups provide a significantly larger entrapment efficacy comparing with their ester counterparts independently of carrier composition and molecular weight. The quantitative understanding of the release mechanism allows guiding the selection of suitable encapsulating polyesters to tune initial burst and long time release of a given drug. Finally, it is demonstrated on cultures of Staphylococcus epidermidis that the encapsulated and subsequently released OHC has conserved its antiseptic activity, which supports the potential applicability of the approach. [ABSTRACT FROM AUTHOR]

The global pollution caused by plastics and microplastics is stimulating intense research towards more environmentally friendly materials, preserving the remarkable application characteristics of the currently available polymers. Among these, polyhydroxyalkanoates (PHAs) have been hailed as the solution to replace conventional, oil-based plastics. Given their biodegradable nature and mechanical properties, their use can be envisioned in a wide range of applications reducing the environmental footprint. Several types of processes have been proposed for their production, which can be grouped in three main classes: (i) microbiological, (ii) enzymatic and (iii) chemical processes. Given the significant amount of literature available on this topic, this review aims to critically analyse what has been proposed so far in each of these classes, with specific reference to their potential to provide bioplastics that can actually replace the currently available materials. A comparison is made, based on the following aspects: achievable molecular structures (such as molecular weight and composition distributions), raw-material and production costs and availability of large-scale production technologies. Finally, some considerations and ideas on what should be further investigated and implemented to realize the economically sustainable production of PHA are brought forward. • The accumulation of plastics in the environment needs to be stopped. • We need bioplastics with the same thermomechanical properties as existing polymers. • PHAs, biodegradable polyesters, are currently one of the most promising solutions. • Critical contrast of production routes: properties, costs and industrial know-how. • Assessing the industrial potential of PHAs is needed to address future research. [ABSTRACT FROM AUTHOR]