Supermacroporous Polymer-Based Cryogel Bioreactor for Monoclonal Antibody Production in Continuous Culture Using Hybridoma Cells

Cryogel matrices composed of different polymeric blends were synthesized, yielding a unique combination of hydrophilicity and hydrophobicity with the presence or absence of charged surface. Four such cryogel matrices composed of polyacrylamide-chitosan (PAAC), poly(N-isopropylacrylamide)-chitosan, polyacrylonitrile (PAN), and poly(N-isopropylacrylamide) were tested for growth of different hybridoma cell lines and production of antibody in static culture. All the matrices were capable for the adherence of hybridoma cell lines 6A4D7, B7B10, and H9E10 to the polymeric surfaces as well as for the efficient monoclonal antibody (mAb) production. PAAC proved to be relatively better in terms of both mAb production and cell growth. Further, PAAC cryogel was designed into three different formats, monolith, disks, and beads, and used as packing material for packed-bed bioreactor. Longterm cultivation of 6A4D7 cell line on PAAC cryogel scaffold in all the three formats could be successfully done for a period of 6 weeks under static conditions. Continuous packed-bed bioreactor was setup using 6A4D7 hybridoma cell line in the three reactor formats. The reactors ran continuously for a period of 60 days during which mAb production and metabolism of cells in the bioreactors were monitored periodically. The monolith bioreactor performed most efficiently over a period of 60 days and produced a total of 57.5 mg of antibody in the first 30 days (in 500 mL) with a highest concentration of 115 mu g mL(-1), which is fourfold higher than t-flask culture. The results demonstrate that appropriate chemistry and geometry of the bioreactor matrix for cell growth and immobilization can enhance the reactor productivity. (C) 2010 American Institute of Chemical Engineers Biotechnol. Prog., 27: 170-180, 2011

Combined Effect of Cryogel Matrix and Temperature-Reversible Soluble-Insoluble Polymer for the Development of in Vitro Human Liver Tissue

Hepatic cell culture on a three-dimensional (3D) matrix or as a hepatosphere appears to be a promising in vitro biomimetic system for liver tissue engineering applications. In this study, we have combined the concept of a 3D scaffold and a spheroid culture to develop an in vitro model to engineer liver tissue for drug screening. We have evaluated the potential of poly(ethylene glycol)-alginate-gelatin (PAG) cryogel matrix for in vitro culture of human liver cell lines. The synthesized cryogel matrix has a flow rate of 7 mL/min and water uptake capacity of 94% that enables easy nutrient transportation in the in vitro cell culture. Youngs modulus of 2.4 kPa and viscoelastic property determine the soft and elastic nature of synthesized cryogel. Biocompatibility of PAG cryogel was evaluated through MTT assay of HepG2 and Huh-7 cells on matrices. The proliferation and functionality of the liver cells were enhanced by culturing hepatic cells as spheroids (hepatospheres) on the PAG cryogel using temperature-reversible soluble-insoluble polymer, poly(N-isopropylacrylamide) (PNIPAAm). Pore size of the cryogel above 100 mu m modulated spheroid size that can prevent hypoxia condition within the spheroid culture. Both the hepatic cells have shown a significant difference (P < 0.05) in terms of cell number and functionality when cultured with PNIPAAm. After 10 days of culture using 0.05% PNIPAAm, the cell number increased by 11- and 7-fold in case of HepG2 and Huh-7 cells, respectively. Similarly, after 10 days of hepatic spheroids culture on PAG cryogel, the albumin production, urea secretion, and CYP450 activity were significantly higher in case of culture with PNIPAAm. The developed tissue mass on the PAG cryogel in the presence of PNIPAAm possess polarity, which was confirmed using F-actin staining and by presence of intercellular bile canalicular lumen. The developed cryogel matrix supports liver cells proliferation and functionality and therefore can be used for in vitro and in vivo drug testing.

Novel pH- and temperature-responsive block copolymers with tunable pH-responsive range

A series of novel pH- and temperature-responsive diblock copolymers composed of poly(N-isopropylacrylamide) (PNIPAM) and poly[(L-glutamic acid)-co-(gamma-benzyl L-glutamate)] [P(GA-co-BLG)] were prepared. The influence of hydrophobic benzyl groups on the phase transition of the copolymers was studied for the first time. With increasing BLG content in P(GA-co-BLG) block, the thermal phase transition of the diblock copolymer became sharper at a designated pH and the critical curve of phase diagram of the diblock copolymer shifted to a higher pH region.

Recent developments in intelligent biomedical polymers

Intelligent polymers or stimuli-responsive polymers may exhibit distinct transitions in physical-chemical properties, including conformation, polarity, phase structure and chemical composition in response to changes in environmental stimuli. Due to their unique 'intelligent' characteristics, stimuli-sensitive polymers have found a wide variety of applications in biomedical and nanotechnological fields. This review focuses on the recent developments in biomedical application of intelligent polymer systems, such as intelligent hydrogel systems, intelligent drug delivery systems and intelligent molecular recognition systems. Also, the possible future directions for the application of these intelligent polymer systems in the biomedical field are presented.

Preparation and Characterization of Nanostructured and High Transparent Hydrogel Films with pH Sensitivity and Application

Novel nanostructured, high transparent, and pH sensitive poly(2-hydroxyethyl methacrylate-co-methacryliac acid)/poly(vinyl alcohol) (P(HEMA-co-MA)/PVA) interpenetrating polymer network (IPN) hydrogel films were prepared by precipitation copolymerization of aqueous phase and sequential IPN technology. The first P(HEMA-co-MA) network was synthesized in aqueous solution of PVA, then followed by aldol condensation reaction, it formed multiple IPN nanostructured hydrogel film. The film samples were characterized by IR, SEM, DSC, and UV-vis spectrum. The transmittance arrived at 93%. Swelling and deswelling behaviors showed the multiple IPN nanostructured film had rapid response. The mechanical properties of all the IPN films improved than that of PVA film. Using crystal violet as a model drug, the release behaviors of the films were studied.

Synthesis of biodegradable thermo- and pH-responsive hydrogels for controlled drug release

Novel intelligent hydrogels composed of biodegradable and pH-sensitive poly(L-glutamic acid) (PGA) and temperature sensitive poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (PNH) were synthesized and characterized for controlled release of hydrophilic drug. The influence of pH on the equilibrium swelling ratios of the hydrogels was investigated. A higher PNH content resulted in lower equilibrium swelling ratios. Although temperature had little influence on the swelling behaviors of the hydrogels, the changes of optical transmittance of hydrogels as a function of temperature were marked, which showed that the PNH part of hydrogel exhibited hydrophobic property at temperature above the lower critical solution temperature (LCST). The biodegradation rate of the stimuli-sensitive hydrogels in the presence of enzyme was directly proportional to the PGA content. Lysozyme was chosen as a model drug and loaded into the hydrogels.

Colloidal microgel in removal of water from biodiesel

A series of poly(N-isopropylacrylamide) [pNIPAM]-based homo-polymer and co-polymer microgel particles were prepared by surfactant-free emulsion polymerisation. The co-monomers were acrylic acid. 4-vinylpyridine. butyl acrylate, 4-vinylbiphenyl and vinyl laurate. Co-monomers were added at a concentration of 10% (w/w) relative to the base monomer pNIPAM for the preparation of each co-polymer microgel. The co-monomers chosen vary by their organic chain length, polarity and pH sensitivity, as these should influence how the particles behave in aqueous and non-aqueous solvents. The effect of adding different types of co-monomer into the microgel structure was investigated with respect to their dispersibility in different solvents. These microgel particles have shown useful application in the removal of water from biodiesel prepared from rape seed. Karl Fischer experiments showed that microgel particles can be used to reduce the water content in biodiesel to an acceptable level for incorporation into internal combustion engines. (C) 2008 Elsevier B.V. All rights reserved.

Synthesis and properties of polyelectrolyte microgel particles

A series of cationic poly(N-isopropylacrylamide/4-vinylpyridine) [poly(NIPAM/4-VP)] polyelectrolyte co-polymer microgels have been prepared by surfactant free emulsion polymerization (SFEP) with varying compositions of 4-VP and NIPAM. The compositions of 4-VP were 15, 25, 35, 45, 55 wt.% relative to NIPAM. The temperature and pH responsive swelling–deswelling properties of these microgels have been investigated using dynamic light scattering (DLS) and electrophoretic mobility measurements. DLS results have shown that the particle diameter of the poly(NIPAM/4-VP) microgels decreases with increasing concentration (wt.%) of 4-VP over the 20–60 °C temperature range due to the increased amount of hydrophobic group. The particle size of all poly(NIPAM/4-VP) microgel series increases with decreasing pH, as the 4-VP units become more protonated at low pH below the pKa (5.39) of the monomer 4-VP. Electrophoretic mobility results have shown that electrophoretic mobility increases as the temperature/pH increases at a constant background ionic strength (1 × 10− 4 mol dm− 3 NaCl). These results are in good agreement with DLS results. The temperature/pH sensitivity of these microgels depends on the ratio of NIPAM/4-VP concentration in the co-polymer microgel systems. The combined temperature/pH responsiveness of these polyelectrolyte microgels can be used in applications where changes in particle size with small change in pH or temperature is of great consequence.

Quantitative mapping of aqueous microfluidic temperature with sub-degree resolution using fluorescence lifetime imaging microscopy

The use of a water-soluble, thermo-responsive polymer as a highly sensitive fluorescence-lifetime probe of microfluidic temperature is demonstrated. The fluorescence lifetime of poly(N-isopropylacrylamide) labelled with a benzofurazan fluorophore is shown to have a steep dependence on temperature around the polymer phase transition and the photophysical origin of this response is established. The use of this unusual fluorescent probe in conjunction with fluorescence lifetime imaging microscopy (FLIM) enables the spatial variation of temperature in a microfluidic device to be mapped, on the micron scale, with a resolution of less than 0.1 degrees C. This represents an increase in temperature resolution of an order of magnitude over that achieved previously by FLIM of temperature-sensitive dyes

Caractérisation de la pharmacocinétique de formulations sensibles au pH et de formulations destinées au traitement des intoxications médicamenteuses

La préparation de formulations à libération contrôlée est le domaine des sciences pharmaceutiques qui vise à modifier l’environnement immédiat des principes actifs pour en améliorer l’efficacité et l’innocuité. Cet objectif peut être atteint en modifiant la cinétique de circulation dans le sang ou la distribution dans l’organisme. Le but de ce projet de recherche était d’étudier le profil pharmacocinétique (PK) de différentes formulations liposomales. L’analyse PK, généralement employée pour représenter et prédire les concentrations plasmatiques des médicaments et de leurs métabolites, a été utilisée ici pour caractériser in vivo des formulations sensibles au pH servant à modifier la distribution intracellulaire de principes actifs ainsi que des liposomes destinés au traitement des intoxications médicamenteuses. Dans un premier temps, la PK d’un copolymère sensible au pH, à base de N-isopropylacrylamide (NIPAM) et d’acide méthacrylique (MAA) a été étudiée. Ce dernier, le p(NIPAM-co-MAA) est utilisé dans notre laboratoire pour la fabrication de liposomes sensibles au pH. L’étude de PK conduite sur les profils de concentrations sanguines de différents polymères a défini les caractéristiques influençant la circulation des macromolécules dans l’organisme. La taille des molécules, leur point de trouble ainsi que la présence d’un segment hydrophobe à l’extrémité des chaînes se sont avérés déterminants. Le seuil de filtration glomérulaire du polymère a été évalué à 32 000 g/mol. Finalement, l’analyse PK a permis de s’assurer que les complexes formés par la fixation du polymère à la surface des liposomes restaient stables dans le sang, après injection par voie intraveineuse. Ces données ont établi qu’il était possible de synthétiser un polymère pouvant être adéquatement éliminé par filtration rénale et que les liposomes sensibles au pH préparés avec celui-ci demeuraient intacts dans l’organisme. En second lieu, l’analyse PK a été utilisée dans le développement de liposomes possédant un gradient de pH transmembranaire pour le traitement des intoxications médicamenteuses. Une formulation a été développée et optimisée in vitro pour capturer un médicament modèle, le diltiazem (DTZ). La formulation liposomale s’est avérée 40 fois plus performante que les émulsions lipidiques utilisées en clinique. L’analyse PK des liposomes a permis de confirmer la stabilité de la formulation in vivo et d’analyser l’influence des liposomes sur la circulation plasmatique du DTZ et de son principal métabolite, le desacétyldiltiazem (DAD). Il a été démontré que les liposomes étaient capables de capturer et de séquestrer le principe actif dans la circulation sanguine lorsque celui-ci était administré, par la voie intraveineuse. L’injection des liposomes 2 minutes avant l’administration du DTZ augmentait significativement l’aire sous la courbe du DTZ et du DAD tout en diminuant leur clairance plasmatique et leur volume de distribution. L’effet de ces modifications PK sur l’activité pharmacologique du médicament a ensuite été évalué. Les liposomes ont diminué l’effet hypotenseur du principe actif administré en bolus ou en perfusion sur une période d’une heure. Au cours de ces travaux, l’analyse PK a servi à établir la preuve de concept que des liposomes possédant un gradient de pH transmembranaire pouvaient modifier la PK d’un médicament cardiovasculaire et en diminuer l’activité pharmacologique. Ces résultats serviront de base pour le développement de la formulation destinée au traitement des intoxications médicamenteuses. Ce travail souligne la pertinence d’utiliser l’analyse PK dans la mise au point de vecteurs pharmaceutiques destinés à des applications variées. À ce stade de développement, l’aspect prédictif de l’analyse n’a pas été exploité, mais le côté descriptif a permis de comparer adéquatement diverses formulations et de tirer des conclusions pertinentes quant à leur devenir dans l’organisme.

Formation et propriétés des cristaux colloïdaux issus de l’auto-assemblage de microsphères de polymère

Le besoin pour des biocapteurs à haute sensibilité mais simples à préparer et à utiliser est en constante augmentation, notamment dans le domaine biomédical. Les cristaux colloïdaux formés par des microsphères de polymère ont déjà prouvé leur fort potentiel en tant que biocapteurs grâce à l’association des propriétés des polymères et à la diffraction de la lumière visible de la structure périodique. Toutefois, une meilleure compréhension du comportement de ces structures est primordiale avant de pouvoir développer des capteurs efficaces et polyvalents. Ce travail propose d’étudier la formation et les propriétés des cristaux colloïdaux résultant de l’auto-assemblage de microsphères de polymère en milieu aqueux. Dans ce but, des particules avec différentes caractéristiques ont été synthétisées et caractérisées afin de corréler les propriétés des particules et le comportement de la structure cristalline. Dans un premier temps, des microsphères réticulées de polystyrène anioniques et cationiques ont été préparées par polymérisation en émulsion sans tensioactif. En variant la quantité de comonomère chargé, le chlorure de vinylbenzyltriméthylammonium ou le sulfonate styrène de sodium, des particules de différentes tailles, formes, polydispersités et charges surfaciques ont été obtenues. En effet, une augmentation de la quantité du comonomère ionique permet de stabiliser de façon électrostatique une plus grande surface et de diminuer ainsi la taille des particules. Cependant, au-dessus d’une certaine concentration, la polymérisation du comonomère en solution devient non négligeable, provoquant un élargissement de la distribution de taille. Quand la polydispersité est faible, ces microsphères chargées, même celles non parfaitement sphériques, peuvent s’auto-assembler et former des cristaux colloïdaux diffractant la lumière visible. Il semble que les répulsions électrostatiques créées par les charges surfaciques favorisent la formation de la structure périodique sur un grand domaine de concentrations et améliorent leur stabilité en présence de sel. Dans un deuxième temps, le besoin d’un constituant stimulable nous a orientés vers les structures cœur-écorce. Ces microsphères, synthétisées en deux étapes par polymérisation en émulsion sans tensioactif, sont formées d’un cœur de polystyrène et d’une écorce d’hydrogel. Différents hydrogels ont été utilisés afin d’obtenir des propriétés différentes : le poly(acide acrylique) pour sa sensibilité au pH, le poly(N-isopropylacrylamide) pour sa thermosensibilité, et, enfin, le copolymère poly(N-isopropylacrylamide-co-acide acrylique) donnant une double sensibilité. Ces microsphères forment des cristaux colloïdaux diffractant la lumière visible à partir d’une certaine concentration critique et pour un large domaine de concentrations. D’après les changements observés dans les spectres de diffraction, les stimuli ont un impact sur la structure cristalline mais l’amplitude de cet effet varie avec la concentration. Ce comportement semble être le résultat des changements induits par la transition de phase volumique sur les interactions entre particules plutôt qu’une conséquence du changement de taille. Les interactions attractives de van der Waals et les répulsions stériques sont clairement affectées par la transition de phase volumique de l’écorce de poly(N-isopropylacrylamide). Dans le cas des microsphères sensibles au pH, les interactions électrostatiques sont aussi à considérer. L’effet de la concentration peut alors être mis en relation avec la portée de ces interactions. Finalement, dans l’objectif futur de développer des biocapteurs de glucose, les microsphères cœur-écorce ont été fonctionnalisées avec l’acide 3-aminophénylboronique afin de les rendre sensibles au glucose. Les effets de la fonctionnalisation et de la complexation avec le glucose sur les particules et leur empilement périodique ont été examinés. La structure cristalline est visiblement affectée par la présence de glucose, même si le mécanisme impliqué reste à élucider.

The effects of additives and chemical modification on the solution properties of thermo-sensitive polymers

Cette thèse concerne l’étude de phase de séparation de deux polymères thermosensibles connus-poly(N-isopropylacylamide) (PNIPAM) et poly(2-isopropyl-2-oxazoline) (PIPOZ). Parmi des études variées sur ces deux polymères, il y a encore deux parties de leurs propriétés thermiques inexplicites à être étudiées. Une partie concerne l’effet de consolvant de PNIPAM dans l’eau et un autre solvant hydromiscible. L’autre est l’effet de propriétés de groupes terminaux de chaînes sur la séparation de phase de PIPOZ. Pour ce faire, nous avons d’abord étudié l’effet de l’architecture de chaînes sur l’effet de cosolvant de PNIPAMs dans le mélange de méthanol/eau en utilisant un PNIPAM en étoile avec 4 branches et un PNIPAM cyclique comme modèles. Avec PNIPAM en étoile, l’adhérence de branches PNIPAM de à un cœur hydrophobique provoque une réduction de Tc (la température du point de turbidité) et une enthalpie plus faible de la transition de phase. En revanche, la Tc de PNIPAM en étoile dépend de la masse molaire de polymère. La coopérativité de déhydratation diminue pour PNIPAM en étoile et PNIPAM cyclique à cause de la limite topologique. Une étude sur l’influence de concentration en polymère sur l’effet de cosolvant de PNIPAM dans le mélange méthanol/eau a montré qu’une séparation de phase liquide-liquide macroscopique (MLLPS) a lieu pour une solution de PNIPAM dans le mélange méthanol/eau avec la fraction molaire de méthanol entre 0.127 et 0.421 et la concentration en PNIPAM est constante à 10 g.L-1. Après deux jours d’équilibration à température ambiante, la suspension turbide de PNIPAM dans le mélange méthanol/eau se sépare en deux phases dont une phase possède beaucoup plus de PNIPAM que l’autre. Un diagramme de phase qui montre la MLLPS pour le mélange PNIPAM/eau/méthanol a été établi à base de données expérimentales. La taille et la morphologie de gouttelettes dans la phase riche en polymère condensée dépendent de la fraction molaire de méthanol. Parce que la présence de méthanol influence la tension de surface des gouttelettes liquides, un équilibre lent de la séparation de phase pour PNIPAM/eau/méthanol système a été accéléré et une séparation de phase liquide-liquide macroscopique apparait. Afin d’étudier l’effet de groupes terminaux sur les propriétés de solution de PIPOZ, deux PIPOZs téléchéliques avec groupe perfluorodécanyle (FPIPOZ) ou groupe octadécyle (C18PIPOZ) comme extrémités de chaîne ont été synthétisés. Les valeurs de Tc des polymères téléchéliques ont beaucoup diminué par rapport à celle de PIPOZ. Des micelles stables se forment dans des solutions aqueuses de polymères téléchéliques. La micellization et la séparation de phase de ces polymères dans l’eau ont été étudiées. La séparation de phase de PIPOZs téléchéliques suit le mécanisme de MLLPS. Des différences en tailles de gouttelettes formées à l’intérieur de solutions de deux polymères ont été observées. Pour étudier profondément les différences dans le comportement d’association entre deux polymères téléchéliques, les intensités des signaux de polymères correspondants et les temps de relaxation T1, T2 ont été mesurés. Des valeurs de T2 de protons correspondants aux IPOZs sont plus hautes.

A new way to nanostructure hydrogels : electrospun thermo-responsive islands-in-the-sea nanofibres

Islands-in-the-sea nanofibres are a very interesting system: one polymer (islands) is distributed in fibrillar domains within a second polymer (sea). This fibre geometry is often used in microfiber technologies to obtain very fine fibers, by removing the “sea” polymer. This geometry also allows to combine two polymers with very different properties. In this work this geometry is introduced applied to electrospun hydrogel nanofibers, in a novel fashion, and as a way to improve and stabilize the hydrogel nanofibers. Thermo-responsive islands-in-the-sea nanofibers are here produced by electrospinning solutions of a hydrogel-forming thermo-responsive polymer (crosslinked poly(N-isopropylacrylamide), PNIPAM) and a reinforcing polymer (polyetherketone cardo, PEK-c). The two polymers are thermodynamically incompatible in solution and phase separation takes place, which allows the instant formation of islands-in-the-sea nanofibers upon electrospinning. PNIPAM was then crosslinked post-spinning using an oligomeric silsesquioxane. The formed nanocomposite nanofibers showed intrinsic nanostructure, where the fibril-like PNIPAM domains are intimately adjacent to the strong PEK-c domains. Upon contacting with water, the hydrogel domains became instantly highly swollen, while the PEK-c domains did not. As a result, very wrinkly, swollen fibers were obtained, with increased capillary action, as demonstrated through confocal microscopy. The composite nanofibers in water showed excellent swelling ratios and very fast responses to temperature variations (of the order of 1 second) with morphological and optical effects: variations in fiber-diameter were accompanied by optical transitions: transparent-opaque. The produced hydrogel nanofibers also presented improved mechanical properties (even with small amounts of PEK-c), when compared to their crosslinked-PNIPAM-only nanofibers. It will be also shown how these materials can be used as optical actuators and smart hydrogel platforms with tuneable contact angle and morphology. In brief, this work aims to demonstrate a new platform technology which can be applied to several hydrogel systems, to achieve hydrogel-based composites with new and improved properties, while retaining (and improving) the main properties of the hydrogel. Here this was demonstrated by showing that the composite materials showed thermo-responsiveness, and enhanced transition kinetics.

Partículas inteligentes de poli (nisopropilacrilamida), quitosana e poli (ácido acrílico): efeito da temperatura e do pH sobre suas propriedades em suspensões aquosas

The present study describes the stability and rheological behavior of suspensions of poly (N-isopropylacrylamide) (PNIPAM), poly (N-isopropylacrylamide)-chitosan (PNIPAMCS), and poly (N-isopropylacrylamide)-chitosan-poly (acrylic acid) (PNIPAM-CS-PAA) crosslinked particles sensitive to pH and temperature. These dual-sensitive materials were simply obtained by one-pot method, via free-radical precipitation copolymerization with potassium persulfate, using N,N -methylenebisacrylamide (MBA) as a crosslinking agent. Incorporation of the precursor materials into the chemical networks was confirmed by elementary analysis and infrared spectroscopy. The influence of external stimuli such as pH and temperature, or both, on particle behavior was investigated through rheological measurements, visual stability tests and analytical centrifugation. The PNIPAM-CS particles showed higher stability in acid and neutral media, whereas PNIPAM-CS-PAA particles were more stable in neutral and alkaline media, both below and above the LCST of poly (Nisopropylacrylamide) (stability data). This is due to different interparticle interactions, as well as those between the particles and the medium (also evidenced by rheological data), which were also influenced by the pH and temperature of the medium. Based on the results obtained, we found that the introduction of pH-sensitive polymers to crosslinked poly (Nisopropylacrylamide) particles not only produced dual-sensitive materials, but allowed particle stability to be adjusted, making phase separation faster or slower, depending on the desired application. Thus, it is possible to adapt the material to different media

Avaliação das propriedades físico-químicas de sistemas a base de carboximetilcelulose e poli (N-isopropilacrilamida) em soluções aquosas para aplicação na indústria do petróleo

Sustainable development is a major challenge in the oil industry and has aroused growing interest in research to obtain materials from renewable sources. Carboxymethylcellulose (CMC) is a polysaccharide derived from cellulose and becomes attractive because it is water-soluble, renewable, biodegradable and inexpensive, as well as may be chemically modified to gain new properties. Among the derivatives of carboxymethylcellulose, systems have been developed to induce stimuli-responsive properties and extend the applicability of multiple-responsive materials. Although these new materials have been the subject of study, understanding of their physicochemical properties, such as viscosity, solubility and particle size as a function of pH and temperature, is still very limited. This study describes systems of physical blends and copolymers based on carboxymethylcellulose and poly (N-isopropylacrylamide) (PNIPAM), with different feed percentage compositions of the reaction (25CMC, 50CMC e 75CMC), in aqueous solution. The chemical structure of the polymers was investigated by infrared and CHN elementary analysis. The physical blends were analyzed by rheology and the copolymers by UV-visible spectroscopy, small-angle X-ray scattering (SAXS), dynamic light scattering (DLS) and zeta potential. CMC and copolymer were assessed as scale inhibitors of calcium carbonate (CaCO3) using dynamic tube blocking tests and chemical compatibility tests, as well as scanning electron microscopy (SEM). Thermothickening behavior was observed for the 50 % CMC_50 % PNIPAM and 25 % CMC_75 % PNIPAM physical blends in aqueous solution at concentrations of 6 and 2 g/L, respectively, depending on polymer concentration and composition. For the copolymers, the increase in temperature and amount of PNIPAM favored polymer-polymer interactions through hydrophobic groups, resulting in increased turbidity of polymer solutions. Particle size decreased with the rise in copolymer PNIPAM content as a function of pH (3-12), at 25 °C. Larger amounts of CMC result in a stronger effect of pH on particle size, indicating pH-responsive behavior. Thus, 25CMC was not affected by the change in pH, exhibiting similar behavior to PNIPAM. In addition, the presence of acidic or basic additives influenced particle size, which was smaller in the presence of the additives than in distilled water. The results of zeta potential also showed greater variation for polymers in distilled water than in the presence of acids and bases. The lower critical solution temperature (LCST) of PNIPAM determined by DLS corroborated the value obtained by UV-visible spectroscopy. SAXS data for PNIPAM and 50CMC indicated phase transition when the temperature increased from 32 to 34 °C. A reduction in or absence of electrostatic properties was observed as a function of increased PNIPAM in copolymer composition. Assessment of samples as scale inhibitors showed that CMC performed better than the copolymers. This was attributed to the higher charge density present in CMC. The SEM micrographs confirmed morphological changes in the CaCO3 crystals, demonstrating the scale inhibiting potential of these polymers