Hydrogel: Preparation, characterization, and applications: A review

Thermo- and pH-responsive polymers in drug delivery.

Polymers that can respond to external stimuli are of great interest in medicine, especially as controlled drug release vehicles. In this critical review, we consider the types of stimulus response used in therapeutic applications and the main classes of responsive materials developed to date. Particular emphasis is placed on the wide-ranging possibilities for the biomedical use of these polymers, ranging from drug delivery systems and cell adhesion mediators to controllers of enzyme function and gene expression (134 references).

Stimuli responsive polymers for biomedical applications

FTIR spectroscopy characterization of poly (vinyl alcohol) hydrogel with different hydrolysis degree and chemically crosslinked with glutaraldehyde

New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive “smart” MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.

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Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

Hydrogels show a strong swelling ability in dependence on pH value or solvent concentration in aqueous solutions. This behavior can be used for appropriate sensors if a suitable transducer transforms the volume change into an electrical output signal. In this work, piezoresistive sensors were used where the hydrogel led to a deflection of the silicon membrane within the sensor chip. This principle allows for a strict separation of the fluid from piezoresistors as well as from other electronic components at the sensor chip front side. Poly(vinyl alcohol)/poly(acrylic acid) (PVA/PAA) blend as well as poly( N -isopropylacrylamide) (PNIPAAm) have been applied and investigated for pH sensors and organic solvent concentration sensors, respectively. The output voltage versus pH value characteristics and the long-term signal stability of hydrogel-based sensors were investigated and the measurement conditions necessary for high signal reproducibility were determined. The influence of the preparation conditions of the hydrogel films on the sensitivity and response time of the chemical and pH sensors is discussed.

Chemical and pH sensors based on the swelling behavior of hydrogels

Temperature and pH sensitive polymers were prepared by the copolymerization of N-isopropylacrylamide (NIPAAm) with varying amounts of acrylamide derivatives bearing carboxylic groups attached to spacers with different chain length (C n AAm). Aqueous solutions of the copolymers show lower critical solution temperature behaviour (LCST). The LCSTs of the aqueous solutions of these copolymers decrease with increasing comonomer content and spacer chain length. Through the use of suitable amounts of the monomers it was possible to accurately predict the phase transition temperature and values were obtained between 10 and 32°C. The LCSTs also strongly depend on the pH-value of the solution. An increase of the pH-value leads to a significant increase in LCST due to the formation of a more hydrophilic copolymer. Through altering the pH it is possible to obtain phase transition temperatures between 10 to 50°C. The LCST behaviour was investigated by means of DSC as a standard method which allows the measurement of the phase transition over a wide range of temperatures and pH-values. Comparison of these results with those from other methods (mainly turbidimetric and viscosimetric measurements) shows a two step mechanism for the phase separation. Dependence of the phase transition temperature of aqueous P(NIPAAm co C 2 AAm) copolymer solutions on the pH-value (lines were drawn to make the diagram clearer).

Temperature and pH dependent solubility of novel poly(N‐isopropylacrylamide)‐copolymers

WWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWW WWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWW WWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWW WWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWW For any polymer gel, the amount of solvent uptake is dependent upon the chemical nature of the gel and the nature of its environment— solvent composition, temperature, pH, and so on. We discuss the use of different hydrogels based on crosslinked poly(N-isopro- pylacrylamide) and copolymers with basic or acidic groups as materials for flow control. The design of a chemo-mechanical valve is described. The liquid flows directly through a gel actuator, which consists of a cylinder filled with small particles of the sensitive crosslinked polymer. The flow rate as well as the pressure drop is measured in dependence on the solvent properties. The sensitivity of the gels as well as the time behavior of the valve-function is correlated with the dependence of the degree of swelling on the environment and the swelling and shrinking kinetics of the gels. The stimulus must permeate the gel itself before a gel can respond to the stimulus. By NMR-imaging it is possible to follow the transport processes inside the gel in real-time. With the presented experimental arrangement we could show that sensitive polymers can be used for controlling the flow in dependence on temperature, pH and content of organic solvents in water. Furthermore, the synthesis of a photo-crosslinkable sensitive polymer is described, synthesized and suggestions for an application of thin layers of this polymer in micro-system techniques are made. Copyright © 2000 John Wiley & Sons, Ltd.

Application of sensitive hydrogels in flow control

The reversible and reproducible phase transition behavior of “stimuli-responsive” or “smart” hydrogels enables their use as materials for chemical and pH sensors in liquids. Using the quartz crystal microbalance (QCMB) technique, the principal behavior of hydrogel coated single sensors in dependence of changes in pH is presented. The general sensor properties of polyelectrolytic hydrogels, the detection possibilities and limits, and the response time of such sensors were investigated and discussed.

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Characterization of a microgravimetric sensor based on pH sensitive hydrogels

General Properties of Hydrogels.- Synthesis of Hydrogels.- Swelling-Related Processes in Hydrogels.- Modelling and Simulation of the Chemo-Electro-Mechanical Behaviour.- Hydrogels for Chemical Sensors.- Hydrogels for Biosensors.- Hydrogels for Actuators.- Polymer Hydrogels to Enable New Medical Therapies.

Karl-Friedrich Arndt

Papers

Chemical and pH sensors based on the swelling behavior of hydrogels

Temperature and pH dependent solubility of novel poly(N‐isopropylacrylamide)‐copolymers

Application of sensitive hydrogels in flow control

Characterization of a microgravimetric sensor based on pH sensitive hydrogels

Hydrogel sensors and actuators