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Hypothesis: Polymer architecture is known to have significant impact on its adsorption behaviour. Most studies have been concerned with the more concentrated, “close to surface saturation” regime of the isotherm, where complications such as lateral interactions and crowding also additionally affect the adsorption. We compare a variety of amphiphilic polymer architectures by determining their Henry's adsorption constant (kH), which, as with other surface active molecules, is the proportionality constant between surface coverage and bulk polymer concentration in a sufficiently dilute regime. It is speculated that not only the number of arms or branches, but also the position of adsorbing hydrophobes influence the adsorption, and that by controlling the latter the two can counteract each other. Methodology: The Self-consistent field calculation of Scheutjens and Fleer was implemented to calculate the adsorbed amount of polymer for many different polymer architectures including linear, star and dendritic. Using the adsorption isotherms at very low bulk concentrations, we determined the value of kH for these. Findings: It is found that the branched structures (star polymers and dendrimers) can be viewed as analogues of linear block polymers based on the location of their adsorbing units. Polymers containing consecutive trains of adsorbing hydrophobes in all cases showed higher level of adsorption compared to their counterparts, where the hydrophobes were more uniformly distributed on the chains. While increasing the number of branches (or arms for star polymers) also confirmed the known result that the adsorption decreased with the number of arms, this trend can be partially offset by the appropriate choice of the location of anchoring groups.

This work demonstrates for the first-time biobased, temperature-responsive diblock copolymer nanoparticles synthesized by reversible addition-fragmentation chain-transfer (RAFT) aqueous emulsion polymerization-induced self-assembly (PISA). Here, monomers derived from green solvents of the lactic acid portfolio, N,N-dimethyl lactamide acrylate (DMLA) and ethyl lactate acrylate (ELA), were used. First, DMLA was polymerized by RAFT aqueous solution polymerization to produce a hydrophilic PDMLA macromolecular chain transfer agent (macro-CTA), which was chain extended with ELA in water to form amphiphilic PDMLA-b-PELA diblock copolymer nanoparticles by RAFT aqueous emulsion polymerization. PDMLAx homopolymers were synthesized targeting degrees of polymerization, DPx from 25 to 400, with relatively narrow molecular weight dispersities (Đ < 1.30). The PDMLA64-b-PELAy diblock copolymers (DPy = 10-400) achieved dispersities, Đ, between 1.18 and 1.54 with two distinct glass transition temperatures (Tg) identified by differential scanning calorimetry (DSC). Tg(1) (7.4 to 15.7 °C) representative of PELA and Tg(2) (69.1 to 79.7 °C) of PDMLA. Dynamic light scattering (DLS) studies gave particle z-average diameters between 11 and 74 nm (PDI = 0.04 to 0.20). Atomic force microscopy (AFM) showed evidence of spherical particles when dispersions were dried at ∼5 °C and film formation when dried at room temperature. Many of these polymers exhibited a reversible lower critical solution temperature (LCST) in water with a concomitant increase in z-average diameter for the PDMLA-b-PELA diblock copolymer nanoparticles.

In this research, the development and investigation of novel nanoobjects based on biodegradable random polypeptides and synthetic non-degradable glycopolymer poly(2-deoxy-2-meth-acrylamido-D-glucose) were proposed as drug delivery systems. Two different approaches have been applied for preparation of such nanomaterials. The first one includes the synthesis of block-random copolymers consisting of polypeptide and glycopolymer and capable of self-assembly into polymer particles. The synthesis of copolymers was performed using sequential reversible addition-fragmentation chain transfer (RAFT) and ring-opening polymerization (ROP) techniques. Amphiphilic poly(2-deoxy-2-methacrylamido-D-glucose)-b-poly(L-lysine-co-L-phenylalanine) (PMAG-b-P(Lys-co-Phe)) copolymers were then used for preparation of self-assembled nanoparticles. Another approach for the formation of polypeptide-glycopolymer particles was based on the post-modification of preformed polypeptide particles with an oxidized glycopolymer. The conjugation of the polysaccharide on the surface of the particles was achieved by the interaction of the aldehyde groups of the oxidized glycopolymer with the amino groups of the polymer on particle surface, followed by the reduction of the formed Schiff base with sodium borohydride. A comparative study of polymer nanoparticles developed with its cationic analogues based on random P(Lysco-D-Phe), as well as an anionic one––P(Lys-co-D-Phe) covered with heparin––was carried out. In vitro antitumor activity of novel paclitaxel-loaded PMAG-b-P(Lys-co-Phe)-based particles towards A549 (human lung carcinoma) and MCF-7 (human breast adenocarcinoma) cells was comparable to the commercially available Paclitaxel-LANS.

The self-assembly of amphiphilic block-copolymers is a convenient way to obtain soft nanomaterials of different morphology and scale. In turn, the use of a biomimetic approach makes it possible to synthesize polymers with fragments similar to natural macromolecules but more resistant to biodegradation. In this study, we synthesized the novel bio-inspired amphiphilic block-copolymers consisting of poly(N-methacrylamido-D-glucose) or poly(N-vinyl succinamic acid) as a hydrophilic fragment and poly(O-cholesteryl methacrylate) as a hydrophobic fragment. Block-copolymers were synthesized by radical addition–fragmentation chain-transfer (RAFT) polymerization using dithiobenzoate or trithiocarbonate chain-transfer agent depending on the first monomer, further forming the hydrophilic block. Both homopolymers and copolymers were characterized by1 H NMR and Fourier transform infrared spectroscopy, as well as thermogravimetric analysis. The obtained copolymers had low dispersity (1.05–1.37) and molecular weights in the range of ~13,000–32,000. The amphiphilic copolymers demonstrated enhanced thermal stability in comparison with hydrophilic precursors. According to dynamic light scattering and nanoparticle tracking analysis, the obtained amphiphilic copolymers were able to self-assemble in aqueous media into nanoparticles with a hydrodynamic diameter of approximately 200 nm. An investigation of nanoparticles by transmission electron microscopy revealed their spherical shape. The obtained nanoparticles did not demonstrate cytotoxicity against human embryonic kidney (HEK293) and bronchial epithelial (BEAS-2B) cells, and they were characterized by a low uptake by macrophages in vitro. Paclitaxel loaded into the developed polymer nanoparticles retained biological activity against lung adenocarcinoma epithelial cells (A549).

Amphiphilic copolymers capable of extracting membrane proteins directly from lipid bilayers into “native nanodiscs” promise a simpler membrane protein sample preparation procedure for structural and functional studies. Unfortunately, the selection of nanodisc-forming copolymers is currently limited to molecules that are heterogeneous in terms of molecular weight and monomer sequence, limiting their efficacy in extracting membrane proteins. Here, we report the development of a highly alternating copolymer composed of acrylic acid and styrene by taking advantage of the fundamental reactivity ratios of these monomers. We show that these copolymers, which we term AASTY, are effective solubilizers of membrane proteins expressed in mammalian cells by virtue of their structured amphiphilicity. These AASTY copolymers are promising alternatives to styrene-maleic acid copolymers and provide a new chemical platform for structural and functional characterization of integral membrane proteins in native nanodiscs.

Amphiphilic copolymers capable of extracting membrane proteins directly from lipid bilayers into “native nanodiscs” promise a simpler membrane protein sample preparation procedure for structural and functional studies. Unfortunately, the selection of nanodisc-forming copolymers is currently limited to molecules that are heterogeneous in terms of molecular weight and monomer sequence, limiting their efficacy in extracting membrane proteins. Here, we report the development of a highly alternating copolymer composed of acrylic acid and styrene by taking advantage of the fundamental reactivity ratios of these monomers. We show that these copolymers, which we term AASTY, are effective solubilizers of membrane proteins expressed in mammalian cells by virtue of their structured amphiphilicity. These AASTY copolymers are promising alternatives to styrene-maleic acid copolymers and provide a new chemical platform for structural and functional characterization of integral membrane proteins in native nanodiscs.

A trithiocarbonate RAFT agent was modified with a pyridyl disulfide group and used in the direct synthesis of endgroup pyridyl disumde-functionalized homo- and amphiphilic block copolymers of oligo(ethyleneglycol) acrylate (PEG-A) and butyl acrylate (BA). Both the homoand copolymerizations were found to be well controlled via the RAFT mechanism. The NMR analysis indicated that both the homopolymers of PEG-A and the amphiphilic diblock copolymers of PEG-A and BA possessed pyridyl disulfide terminal groups. A UV-Vis absorption test revealed that the pyridyl disulfide endgroup of the polymer could be efficiently used to couple thiol-bearing molecules to the polymer without the need for any post-polymerization modification. This communication presents the first efficient direct synthesis of thiol-reactive endgroup-functionalized well-defined polymers via the RAFT technique. © 2007 WILEY-VCH Verlag GmbH & Co. KGaA.

The development of novel biomaterials needs to move towards a rational design from both a research and commercial point of view. In this context, the rise of combinatorial chemistry approaches and analytical high-throughput methods have been a breakthrough in the design and screening of new materials. In the polymer chemistry field, these methods led to the synthesis of libraries of novel polymers with significant savings in time, materials waste, and labour. Additionally, in the biomaterials screening process, it is important to find new biological alternative tests in order to have a deeper understanding on the interaction of the biomaterials with their immediate extracellular environment and, consequently, derive more realistic biological models/assays that mimic real human conditions. In the work presented here, it was reported the synthesis of novel amphiphilic copolymers presenting target chemistry and biological properties. For the first time, this polymeric amphiphiles were used in a flow-focusing microfluidic apparatus where they acted as surfactants for the production of a library of monodisperse microparticles with bio-instructive surface, to be used as potential 3D platform for controlling surface-cell response. In Chapter 3, a library of new polymeric surfactant materials was designed and synthesised by using a high-throughput synthesiser. In addition, in this chapter, the combination of a novel high-throughput analytical technique and the use of a machine learning analysis delivered ‘on-demand’ product property assessment. Chapter 4 outlines how the use of designed polymeric surfactants and droplet microfluidics can exert control over both the surface chemistry and size distribution of microparticle materials, demonstrating their critical importance for controlling surface-cell response. In Chapter 5 the main aim was to develop and synthesise cationic random and block amphiphilic copolymers, by using two different radical polymerisation techniques. Als