Poly(HPMA)-based copolymers with biodegradable side chains able to self assemble into nanoparticles

N-(2-Hydroxypropyl)methacrylamide (HPMA) is a water soluble monomer used in the synthesis of biocompatible and non-immunogenic polymers. In particular, poly(HPMA) can be exploited to sterically stabilize nanoparticles (NPs) suitable for the delivery of lipophilic therapeutics without the concerns related to the use of the polyethylene glycol (PEG), such as allergic reactions and the accelerated blood clearance effect. In addition, the use of the ring opening polymerization (ROP) of a lactone in the presence of an initiator that bears a double bond and a hydroxyl group is a promising way (the so called “macromonomer method”) to produce oligoester-based monomers and, in turn, to obtain biodegradable NPs via free radical polymerization. However, HPMA cannot be used as initiator being a secondary alcohol and thus hampering the control over the polymer molecular weight (MW). For this reason, in this work, a novel class of amphiphilic block copolymers that consists of a poly(HPMA) backbone and several short oligo(3-caprolactone) side chains were produced via the adoption of the reversible addition– fragmentation chain transfer (RAFT) polymerization and the “inversion” of the macromonomer method. The oligoester was first synthesized via the ROP of 3-caprolactone in the presence of a primary alcohol and then attached to HPMA using a succinic acid unit as spacer. The NPs obtained via the self-assembly of these novel block copolymers are designed to degrade into completely water soluble poly(HPMA) chains with a MW lower than the threshold value for the renal excretion. The cytotoxicity of these novel carriers and their ability to load trabectedin, a hydrophobic anticancer therapeutic, were assessed

Methane Reforming with H2S and Sulfur for Hydrogen Production: Thermodynamic Assessment

Nowadays, most ofthe hydrogen is obtained from fossil fuels. Atthe same time, the effort and resources dedicated to the developmentof sustainable hydrogen manufacturing processes are rapidly increasingto promote the energy transition toward renewable sources. In thisdirection, a potential source of hydrogen could be hydrogen sulfide,produced as a byproduct in several processes, and in particular inthe oil extraction and refinery operations. Methane reforming usingH(2)S has recently attracted much interest for its economicand environmental implications. Its conversion, in fact, providesa viable way for the elimination of a hazardous molecule, producinga high-added value product like hydrogen. At the same time, some ofthe still open key aspects of this process are the coke depositiondue to thermal pyrolysis of methane and the process endothermicity.In this work, the methane reforming with H2S by co-feedingsulfur is investigated through a detailed thermodynamic analysis asa way to alleviate the critical aspects highlighted for the process.A parametric analysis was conducted to assess the best thermodynamicconditions in terms of pressure, temperature, and feed composition.Changing the sulfur, H2S, and methane feed compositioncan enhance the system by improving the hydrogen production yield,reducing the carbon and sulfur deposition, increasing the H2S removal efficiency, and reducing the necessary thermal duty

Chemical recycling of polyethylene terephthalate (PET) to monomers: Mathematical modeling of the transesterification reaction of bis(2-hydroxyethyl) terephthalate to dimethyl terephthalate

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

Thermo-responsive polymers as surface active compounds: A review

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

Functionalized lactic acid macromonomers polycondensation

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Preliminary tests on PEG-based thermoresponsive polymers for the production of 3D bioprinted constructs

In the last years, the growing demand for tissues and organs led to the development of novel techniques, such as 3D bioprinting. This technique proved to be promising for both patient-specific and custom-made applications when using autologous cells, and for the creation of standardized models that in the future could be used for instance for high-throughput drug screening. Within this context, the formulation of bioinks that could provide reliable, reproducible, and replicable structures with good mechanical properties and high biocompatibility is a crucial challenge. In this work, the use of a thermoresponsive PEG-based formulation was investigated as a bioink, allowing its use for 4D bioprinting applications triggered by thermal changes. First, the polymer was synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT), which allows for optimal control over the final properties of the polymer. Then, the printability for extrusion-based bioprinting of this formulation was assessed through in-situ imaging. Finally, the use of this polymer as bioink was tested by encapsulation of endothelial cells and evaluating cell distribution within the construct

Probing the mechanism for hydrogel-based stasis induction in human pluripotent stem cells : is the chemical functionality of the hydrogel important?

It is well-known that pluripotent human embryonic stem cells (hPSC) can differentiate into any cell type. Recently, we reported that hPSC colonies enter stasis when immersed in an extremely soft hydrogel comprising hydroxyl-functional block copolymer worms (I. Canton, N. J. Warren, A. Chahal, K. Amps, A. Wood, R. Weightman, E. Wang, H. Moore and S. P. Armes, ACS Centr. Sci., 2016, 2, 65–74). The gel modulus and chemical structure of this synthetic hydrogel are similar to that of natural mucins, which are implicated in the mechanism of diapause for mammalian embryos. Does stasis induction occur merely because of the very soft nature of such hydrogels or does chemical functionality also play a role? Herein, we address this key question by designing a new hydrogel of comparable softness in which the PGMA stabilizer chains are replaced with non-hydroxylated poly(ethylene glycol) [PEG]. Immunolabeling studies confirm that hPSC colonies immersed in such PEG-based hydrogels do not enter stasis but instead proliferate (and differentiate if no adhesion substrate is present). However, pluripotency is retained if an appropriate adhesion substrate is provided. Thus, the chemical functionality of the hydrogel clearly plays a decisive role in the stasis induction mechanism

A Methodologic Approach for the Selection of Bio-Resorbable Polymers in the Development of Medical Devices: The Case of Poly(L-lactide-co-epsilon-caprolactone)

In the last decades bioresorbable and biodegradable polymers have gained a very good reputation both in research and in industry thanks to their unique characteristics. They are able to ensure high performance and biocompatibility, at the same time avoiding post-healing surgical interventions for device removal. In the medical device industry, it is widely known that product formulation and manufacturing need to follow specific procedures in order to ensure both the proper mechanical properties and desired degradation profile. Moreover, the sterilization method is crucial and its impact on physical properties is generally underestimated. In this work we focused our attention on the effect of different terminal sterilization methods on two commercially available poly(l-lactide-co-ε-caprolactone) with equivalent chemical composition (70% PLA and 30% PCL) and relatively similar initial molecular weights, but different chain arrangements and crystallinity. Results obtained show that crystallinity plays a key role in helping preserve the narrow distribution of chains and, as a consequence, defined physical properties. These statements can be used as guidelines for a better choice of the most adequate biodegradable polymers in the production of resorbable medical devices

Recoverable Thermo-Responsive Polymeric Surfactants for the Synthesis of Bulk Plastics from Latexes

Free-radical emulsion polymerization (eFRP) is widely adopted in industries due to the great advantages that this technique offers in terms of a high polymerization rate, good heat management, and conduction in a non-toxic solvent like water. On the other hand, eFRP requires surfactants to stabilize the produced polymer nanoparticles (NPs). At the same time, the recovery of a bulk material from a NP suspension needs the addition of salts or alkali for the destabilization of the emulsion and the precipitation of the polymer. These can contaminate the final product and affect its properties. For this reason, alternative strategies able to coagulate the NP latex avoiding the addition of exogenous compounds are needed. In this work, we synthesized thermo-responsive polymeric surfactants that are able to promote the NP formation during the eFRP and to allow the recovery of the bulk polymer by simply increasing the environment temperature. Surfactants with a tunable hydrophilic–lipophilic balance were produced through reversible-addition fragmentation chain transfer (RAFT) emulsion polymerization by chain-extending a polyethylene glycol-based macromolecular chain transfer agent with butyl methacrylate, in order to obtain a series of block copolymers with high blocking efficiency, controlled molecular weight distribution, and well-defined thermo-responsive behavior. Then, the RAFT agent was removed to avoid the further extension of the block copolymers, and the surfactants were tested in the eFRP of different monomers (i.e., butyl methacrylate, methyl methacrylate, and styrene) to produce stable NP latexes. Finally, the possibility of triggering the NP aggregation and of guaranteeing the recovery of both surfactants and bulk material by simply changing the temperature of the system was assessed