Role of the Polymer Microstructure in Controlling Colloidal and Thermo-Responsive Properties of Nano-Objects Prepared Via RAFT Polymerization in a Non-polar Medium.

After having demonstrated their potential in biomedical applications, thermo-responsive block copolymers that are able to self-assemble into nano-objects in response to temperature modifications are becoming more and more appealing in other sectors, such as the oil and gas and lubricant fields. Reversible addition-fragmentation chain transfer (RAFT) polymerization-induced self-assembly has been demonstrated as a valuable strategy for producing nano-objects from modular block copolymers in non-polar media, required for the mentioned applications. Although the influence of the nature and size of the thermo-responsive block of these copolymers on the properties of the nano-objects is extensively studied in the literature, the role of the solvophilic block is often neglected. In this work, we elucidate the role of the main microstructural parameters, including those of the solvophilic portion, of block copolymers produced by RAFT polymerization in the hydrocarbon blend decane/toluene 50:50 v/v on the thermo-responsive behavior and colloidal properties of the resulting nano-objects. Two long-aliphatic chain monomers were employed for the synthesis of four macromolecular chain transfer agents (macroCTAs), with increasing solvophilicity according to the number of units (n) or length of the alkyl side chain (q). Subsequently, the macroCTAs were chain-extended with different repeating units of di(ethylene glycol) methyl ether methacrylate (p), leading to copolymers that are able to self-assemble below a critical temperature. We show that this cloud point can be tuned by acting on n, p, and q. On the other hand, the colloidal stability, expressed in terms of area of the particle covered by each solvophilic segment, is only a function of n and q, which provides a way for controlling the size distribution of the nano-objects and to decouple it from the cloud point.

Influence of the Polymer Microstructure over the Phase Separation of Thermo-Responsive Nanoparticles.

Thermo-responsive nanoparticles (NPs), i.e., colloids with a sharp and often reversible phase separation in response to thermal stimuli, are coming to the forefront due to their dynamic behavior, useful in applications ranging from biomedicine to advanced separations and smart optics. What is guiding the macroscopic behavior of these systems above their critical temperature is mainly the microstructure of the polymer chains of which these NPs are comprised. Therefore, a comprehensive understanding of the influence of the polymer properties over the thermal response is highly required to reproducibly target a specific behavior. In this study, we synthesized thermo-responsive NPs with different size, polymeric microstructure and hydrophilic-lipophilic balance (HLB) and investigated the role of these properties over their phase separation. We first synthesized four different thermo-responsive oligomers via Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization of poly(ethylene glycol)methyl ether methacrylate. Then, exploiting the RAFT living character, we chain-extended these oligomers with butyl methacrylate obtaining a library of NPs. Finally, we investigated the NP thermo-responsive behavior, their physical state above the cloud point (Tcp) as well as their reversibility once the stimulus is removed. We concluded that the solid content plays a minor role compared to the relative length of the two blocks forming the polymer chains. In particular, the longer the stabilizer, the more favored the formation of a gel. At the same time, the reversibility is mainly achieved at high HLB, independently from the absolute lengths of the block copolymers.

Limonene-in-water Pickering emulsion and on-demand separation using thermo-responsive biodegradable nanoparticles.

In the last few decades, Pickering emulsions have regained attention due to the possibility of forming stable oil-in-water emulsions with interesting interfacial properties. As an example, the more and more stringent regulations on the products for home and personal care are pushing the market towards the use of biodegradable materials in order to reduce their environmental impact. In this scenario, an appealing opportunity is offered by the use of biodegradable polymeric nanoparticles (NPs) for the stabilization of fragrance oils in water. In this work, modular biodegradable NPs have been synthesized through a combination of ring opening polymerization and reversible addition-fragmentation chain transfer emulsion polymerization and used to produce limonene-in-water Pickering emulsions. This strategy allowed controlling independently the NP size, polymer molecular weight, and hydrophobicity acting on the microstructure of the constituting copolymers. Stable limonene-in-water Pickering emulsions could be obtained, with the size of the oil phase and the wetting by limonene that can be strictly controlled by tuning the NP physico-chemical properties. Finally, the adoption of thermo-responsive polymer chains within the shell of the Pickering emulsifiers enabled the on-demand destabilization of the emulsions and hence the selective dispensing of limonene by simply increasing the temperature.

Oligonucleotides: Current Trends and Innovative Applications in the Synthesis, Characterization, and Purification.

Oligonucleotides (ONs) are gaining increasing importance as a promising novel class of biopharmaceuticals. Thanks to their fundamental role in gene regulation, they can be used to develop custom-made drugs (also called N-to-1) able to act on the gene expression at pre-translational level. With recent approvals of ON-based therapeutics by the Food and Drug Administration (FDA), a growing demand for high-quality chemically modified ONs is emerging and their market is expected to impressively prosper in the near future. To satisfy this growing market demand, a scalable and economically sustainable ON production is needed. In this paper, the state of the art of the whole ON production process is illustrated with the aim of highlighting the most promising routes toward the auspicated market-size production. In particular, the most recent advancements in both the upstream stage, mainly based on solid-phase synthesis and recombinant technology, and the downstream one, focusing on chromatographic techniques, are reviewed. Since ON production is projected to expand to the large scale, automatized multicolumn countercurrent technologies will reasonably be required soon to replace the current ones based on batch single-column operations. This consideration is supported by a recent cutting-edge application of continuous chromatography for the ON purification.

Readily Adsorbable Thermoresponsive Polymers for the Preparation of Smart Cell-Culturing Surfaces on Site.

The efficacy of several cell therapy products is directly impacted by trypsinization, which can diminish the engrafting capacity of transplanted cells by cleaving cell surface receptors. Thermoresponsive surfaces can alleviate this drawback, enabling temperature-driven and enzyme-free cell harvesting. However, the production of thermoresponsive surfaces relies on dedicated and complex equipment, often involving protocols dependent on high surface activation energies that prevent the development of scalable and universal platforms. In this work, we developed thermoresponsive copolymers incorporating styrene units that enable the copolymer adsorption on tissue culture polystyrene surfaces from an alcoholic solution in a short time, regardless of the vessel size and geometry, and without any particular equipment. In this way, the procedure can be performed with minimal effort by the end user on any surface. The thermoresponsive copolymers were synthesized via reversible addition-fragmentation chain transfer polymerization, providing high control over the polymer microstructure, a key parameter for tuning its cloud point and architecture. Block copolymers comprising a thermoresponsive segment and a polystyrene block exhibited optimal adhesion on conventional cell culture surfaces and permitted a more efficient temperature-mediated harvesting of adipose-derived stromal cells and Chinese hamster ovary cells compared to their statistical counterparts. To expand the application of this polymer deposition protocol to serum-free cell culture, we also considered the polymer modification with the tripeptide arginine-glycine-aspartic acid, known to promote the cell adhesion to synthetic substrates. The incorporation of this peptide enabled the collection in serum-free conditions of intact cell sheets from surfaces prepared shortly before their usage.

Zwitterionic Polyester-Based Nanoparticles with Tunable Size, Polymer Molecular Weight, and Degradation Time.

Biodegradable polymer nanoparticles are an important class of materials used in several applications for their unique characteristics. In particular, the ones stabilized by zwitterionic materials are gaining increased interest in medicine as alternative to the more common ones based on poly(ethylene glycol) thanks to their superior stability and ability to avoid both the accelerated blood clearance and allergic reactions. In this work, a novel class of zwitterionic based NPs has been produced, and a method to independently control the nanoparticle size, degradation time, and polymer molecular weight has been developed and demonstrated. This has been possible by the synthesis and the fine-tuning of zwitterionic amphiphilic block copolymers obtained via the combination of ring-opening polymerization and reversible addition-fragmentation chain transfer polymerization. The final results showed that when two block copolymers contain the same number of caprolactone units, the one with longer oligoester lateral chains degrades faster. This phenomenon is in sharp contrast with the one seen so far for the common linear polyester systems where longer chains result in longer degradation times, and it can be used to better tailor the degradation behavior of the nanoparticles.