Stimuli responsive polymers (SRP) have attracted a lot of attention, due to their potential and promising applications in many fields, as protein-ligand recognition, on-off switches for modulated drug delivery or artificial organs. Poly(N-isopropylacrylamide) (PNIPAM) is one of the most widely studied polymers due to its lower critical solution temperature (LCST) at ~ 32° C in aqueous solution. Additionally, glycopolymers, where free sugar units are present, have potentially interesting applications especially in bio-recognition where sugars play an important role. In this work, our interest was focused on the synthesis of glycomonomers and its block- and random- copolymers with NIPAM. NIPAM homopolymers with an active chain transfer unit at the chain end could be prepared by RAFT. They were used as macro-chain transfer agents to prepare a variety of sugar containing responsive block copolymers from new glycomonomers by the monomer addition concept. The LCSTs of the aqueous solutions of the copolymers are affected strongly by the comonomer content, spacer chain length of the glycomonomer and the chain architecture of the copolymers. These polymers were coated on a solid substrate by spin coating and crosslinked by plasma immobilization. Characterization of the polymers was performed by nuclear magnetic resonance spectroscopy (NMR), ultraviolet (UV), dynamic light scattering (DLS, detection of aggregation behaviour) and gel permeation chromatography (GPC). Polymer films were investigated by ellipsometry, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) regarding their surface properties. Afterwards sulfation of sugar – OH groups was performed in order to obtain heparin like structure, as heparin exhibits numerous important biological activities, like good interaction with diverse proteins. Finally, affinity of the polymers (sulfated and non sulfated form) on a solid support to the endothelial cells was investigated.

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<p>Multi-stimuli-responsive materials with dual sensitivities to both temperature and light were designed and investigated for their responsive properties in aqueous media.</p> <p>Amphiphilic polymers were synthesized by copolymerizing monomers of thermoresponsive N-isopropylacrylamide (NIPAM) with vinyl cinnamate (VC), using different chain transfer agents to both control the molecular weight and impart functionality of an amine-terminal or carboxylic acid- terminal end groups. Linear polymers based on pNIPAM-VC were characterized and their thermo- and photo-responsive properties confirmed by ¹H NMR, GPC, and UV-visible spectroscopy.</p> <p>To obtain desired solubility and phase transition properties for the copolymer, latent variable methods were applied to past polymer data to identify the correlated reaction variables. Using model inversion, the ability to predict polymer properties was possible. The outcomes helped to determine ideal reaction reagents and conditions for future designs, facilitating the synthesis of both amine-capped and carboxylic acid-capped poly(NIPAM-co-VC) polymers with high solubility and phase transition onset below physiological temperature (<37°C)</p> <p>The designed poly(NIPAM-co-VC) polymers were subsequently grafted to a polysaccharide, hyaluronic acid (HA) or carboxymethyl cellulose (CMC), via carbodiimide chemistry. The graft material’s mechanical strength was compromised by both the linear polymer size and the architecture (end-group-grafting) which lead to unsuitable materials.</p> <p>Microgels with multi-responsive properties were synthesized by copolymerizing NIPAM with either acrylic acid (AA) or methacrylic acid (MAA) by conventional precipitation-emulsion methods. These microgels were aminated and subsequently grafted with a cinnamate pendant group. As an alternative, microgels were fabricated by microfluidics using linear polymers precursors. Both types of microgels exhibited significant deswelling upon changes in temperature, light, and pH, suggesting their potential utility as smart, photo-responsive drug delivery vehicles.</p> / Master of Applied Science (MASc)

Stimuli responsive polymers (SRP) have attracted a lot of attention, due to their potential and promising applications in many fields, as protein-ligand recognition, on-off switches for modulated drug delivery or artificial organs. Poly(N-isopropylacrylamide) (PNIPAM) is one of the most widely studied polymers due to its lower critical solution temperature (LCST) at ~ 32° C in aqueous solution. Additionally, glycopolymers, where free sugar units are present, have potentially interesting applications especially in bio-recognition where sugars play an important role. In this work, our interest was focused on the synthesis of glycomonomers and its block- and random- copolymers with NIPAM. NIPAM homopolymers with an active chain transfer unit at the chain end could be prepared by RAFT. They were used as macro-chain transfer agents to prepare a variety of sugar containing responsive block copolymers from new glycomonomers by the monomer addition concept. The LCSTs of the aqueous solutions of the copolymers are affected strongly by the comonomer content, spacer chain length of the glycomonomer and the chain architecture of the copolymers. These polymers were coated on a solid substrate by spin coating and crosslinked by plasma immobilization. Characterization of the polymers was performed by nuclear magnetic resonance spectroscopy (NMR), ultraviolet (UV), dynamic light scattering (DLS, detection of aggregation behaviour) and gel permeation chromatography (GPC). Polymer films were investigated by ellipsometry, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) regarding their surface properties. Afterwards sulfation of sugar – OH groups was performed in order to obtain heparin like structure, as heparin exhibits numerous important biological activities, like good interaction with diverse proteins. Finally, affinity of the polymers (sulfated and non sulfated form) on a solid support to the endothelial cells was investigated.

abstract: Hydrogel polymers have been the subject of many studies, due to their fascinating ability to alternate between being hydrophilic and hydrophobic, upon the application of appropriate stimuli. In particular, thermo-responsive hydrogels such as N-Isopropylacrylamide (NIPAM), which possess a unique lower critical solution temperature (LCST) of 32°C, have been leveraged for membrane-based processes such as using NIPAM as a draw agent for forward osmosis (FO) desalination. The low LCST temperature of NIPAM ensures that fresh water can be recovered, at a modest energy cost as compared to other thermally based desalination processes which require water recovery at higher temperatures. This work studies by experimentation, key process parameters involved in desalination by FO using NIPAM and a copolymer of NIPAM and Sodium Acrylate (NIPAM-SA). It encompasses synthesis of the hydrogels, development of experiments to effectively characterize synthesized products, and the measuring of FO performance for the individual hydrogels. FO performance was measured using single layers of NIPAM and NIPAM-SA respectively. The values of permeation flux obtained were compared to relevant published literature and it was found to be within reasonable range. Furthermore, a conceptual design for future large-scale implementation of this technology is proposed. It is proposed that perhaps more effort should focus on physical processes that have the ability to increase the low permeation flux of hydrogel driven FO desalination systems, rather than development of novel classes of hydrogels / Dissertation/Thesis / Masters Thesis Mechanical Engineering 2019

Les laboratoires sur puce sont des dispositifs intégrés rassemblant, sur un substrat miniaturisé, une ou plusieurs fonctions de laboratoire, généralement dédiées à la manipulation d'échantillons chimiques ou biologiques. L'objectif de ces travaux est l'intégration dans les microsystèmes d'un polymère intelligent, le poly(N-isopropylacrylamide) (pnipam), afin de développer une nouvelle filière technologique pour les laboratoires sur puce. Le pnipam est un polymère thermosensible subissant un changement réversible, d'un état hydrophile et gonflé sous sa température de transition (lcst ~32°C) à un état hydrophobe et replié au-delà. La technologie développée repose sur des éléments chauffants et un protocole de greffage du pnipam sur des surfaces. Nos travaux montrent que le contrôle thermique du pnipam permet de moduler le flux électroosmotique, ouvrant ainsi la voie au développement de mélangeurs électrocinétiques. Ce contrôle permet également l'accrochage, partiellement réversible, de protéines sur des billes fonctionnalisées, pour des applications dans le domaine de la préparation d'échantillon.

Poly(N-isopropylacrylamide) (PNIPAM) is a smart polymer exhibiting an inverse temperature-solubility relationship with a sharp transition at 32&deg / C in its aqueous solution. Due to its reversible thermo-responsive phase transition behavior at around body temperature, PNIPAM promise a potential for a variety of novel applications especially in biotechnology and medicine. PNIPAM can be produced by conventional polymerization methods, as well as by use of ionizing radiation, primarily by gamma which leads mainly to a residual-free crosslinked polymer. In this study, RF plasma (glow discharge) technique is used as a novel synthesis method in solid state leading to higher proportions of linear polymer. Since plasma method is an additive-/initiator-free process, a residual-free polymer is expected. To obtain a better understanding of the plasma induced solid state polymerization mechanism of NIPAM, X-ray data are used. It is found that crystalline structures of Acrylamide (AAm) and NIPAM are isomorphous. Plasma and post plasma aging effects on crystalline structure of NIPAM are followed. From the Electron Paramagnetic Resonance (EPR) investigations it is observed that post plasma polymerization of NIPAM in solid state proceed by radicalic mechanism. After determination of temperature range in which the radical formed by plasma treatment of NIPAM is highly stable, decay kinetics of the propagating radical in solid state after plasma treatment has been studied in detail.

Gene expression knockdown using RNA interference has dramatically altered the ability to silence target genes without the need for a creation of a genetic knockout. The pitfalls surrounding successful siRNA gene expression knockdown fall in the broad category of delivery. This work focuses on the use of N-isopropyl-acrylamide conjugated polyglycerol (PGNIPAM) as a novel cationic vector of in vitro and possible in vivo delivery of siRNA. The hyper-branched structure of the PGNIPAM molecule bears a biocompatible core with cationic subunits on the surface, providing a less toxic alternative to other cationic polymers used in the past. Further PGNIPAM shows excellent binding and release characteristics over other comparable molecules and systems. Activity of the siRNA requires access to the cell cytoplasm, which in turn requires passage of the siRNA through the cell membrane and release into the internal environment with no degradation. PGNIPAM has shown the ability to traverse the endocytic pathway and release the siRNA directly into the cytoplasm where it can interact with cellular machinery. Knockdown of known oncogene survivin was observed in vitro both through mRNA expression reduction as well as through protein reduction in MDA-MB-231 human breast cancer cells. Additionally, early stage animal work with a human breast cancer model shows positive results for coupled treatment of tumors using siRNA against survivin and doxorubicin, an anticancer drug. PGNIPAM offers a safer alternative to other cationic delivery systems and has shown improvement over standard modes of knockdown from commercial products.

<p>The mechanical and chemical properties of hydrogels make them excellent vehicles to deliver drugs. However, current systems encounter difficulties with loading hydrophobic molecules into the aqueous gel network and the subsequent release of the drug from the gel matrix. Cyclodextrins (CDs) offer a potential solution to this drug delivery challenge. CDs have the unique property of possessing a hydrophilic exterior and a hydrophobic interior pocket which is capable of hydrophobic drug binding. CD molecules complexed with hydrophobic drugs have been demonstrated to significantly increase the bioavailability of those drugs in free solution. Thus, if these nanodomains are introduced into microgels or hydrogels, we anticipate that significantly higher hydrophobic drug loadings may be achieved together with improved controlled release of these drugs based on the properties of the hydrogel or microgel phase. We have fabricated <em>in situ</em> gellable and degradable hydrogels and microgels based on combinations of CDs and either functionalized carbohydrates (dextran) or thermosensitive synthetic polymers (poly(N-isopropylacrylamide), PNIPAM). To achieve this goal, we designed a series of microgels with grafted or immobilized CD groups and used multi-functional CD as a reactive crosslinker for making injectable bulk hydrogels.</p> / Master of Applied Science (MASc)

N,N′-methylenebisacrylamide-crosslinked poly(N-isopropylacrylamide), also known as P(NIPAM), was developed as a fluid delivery system for use with microfluidic paper-based analytical devices (microPADs). MicroPADs are postage-stamp-sized devices made out of paper that can be used as platforms for low-cost, simple-to-use point-of-care diagnostic assays. P(NIPAM) is a thermally responsive polymer that absorbs aqueous solutions at room temperature and will expel the solutions to microPADs when heated. The fluid delivery characteristics of P(NIPAM) were assessed, and P(NIPAM) was able to deliver multiple solutions to microPADs in specific sequences or simultaneously in a laminar-flow configuration. P(NIPAM) was then shown to be suitable for delivering four classes of reagents to microPADs: small molecules, enzymes, antibodies and DNA. P(NIPAM) successfully delivered a series of standard concentrations of glucose (0 – 5 mM) to microPADs equipped to perform a colorimetric glucose assay. The results of these tests were used to produce an external calibration curve, which in turn was used to determine accurately the concentrations of glucose in sample solutions. P(NIPAM) successfully delivered fluorescein-labeled IgG and fluorescein-labeled oligonucleotides (20 base pairs) to microPADs in a variety of concentrations. P(NIPAM) also successfully delivered horseradish peroxidase (HRP) to microPADs, and it was determined that HRP could be stored in P(NIPAM) for 35 days with minimal loss in activity. The combination of P(NIPAM) with microPADs will allow for more complex assays to be performed with minimal user input, will facilitate the preparation of external calibration curves in the field, and may be useful in extending the shelf life of microPADs by stabilizing reagents.