Hydrogels in pharmaceutical formulations.

Shape memory polymer compositions, articles of manufacture thereof, and methods of preparation and use thereof are described. The shape memory polymer compositions can hold more than one shape in memory. Suitable compositions include at least one hard segment and at least one soft segment. The Ttrans of the hard segment is preferably between -30 and 270 °C. At least one of the hard or soft segments can contain a cross-linkable group, and the segments can be linked by formation of an interpenetrating network or a semi-interpenetrating network, or by physical interactions of the blocks. Objects can be formed into a given shape at a temperature above the Ttrans of the hard segment, and cooled to a temperature below the Ttrans of the soft segment. If the object is subsequently formed into a second shape, the object can return to its original shape by heating the object above the Ttrans of the soft segment and below the Ttrans of the hard segment. The compositions can also include two soft segments which are linked via functional groups which are cleaved in response to application of light, electric field, magnetic field or ultrasound. The cleavage of these groups causes the object to return to its original shape.

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Shape memory polymers

Aconstitutive model is proposed for the deformation of rubber materials which is shown to represent successfully the response of these materials in uniaxial extension, biaxial extension, uniaxial compression, plane strain compression and pure shear. The developed constitutive relation is based on an eight chain representation of the underlying macromolecular network structure of the rubber and the non-Gaussian behavior of the individual chains in the proposed network. The eight chain model accurately captures the cooperative nature of network deformation while requiring only two material parameters, an initial modulus and a limiting chain extensibility. Since these two parameters are mechanistically linked to the physics of molecular chain orientation involved in the deformation of rubber, the proposed model represents a simple and accurate constitutive model of rubber deformation. The chain extension in this network model reduces to a function of the root-mean-square of the principal applied stretches as a result of effectively sampling eight orientations of principal stretch space. The results of the proposed eight chain model as well as those of several prominent models are compared with experimental data of Treloar (1944, Trans. Faraday Soc. 40, 59) illustrating the superiority, simplicity and predictive ability of the proposed model. Additionally, a new set of experiments which captures the state of deformation dependence of rubber is described and conducted on three rubber materials. The eight chain model is found to model and predict accurately the behavior of the three tested materials further confirming its superiority and effectiveness over earlier models.

https://hal.archives-ouvertes.fr/hal-01390807/document

A three-dimensional constitutive model for the large stretch behavior of rubber elastic materials

Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.

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Designing hydrogels for controlled drug delivery.

Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field.

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Hydrogels in regenerative medicine

The interaction of solvents with cross‐linked network structures, such as occur in vulcanized rubber, is subjected to a statistical mechanical treatment based on the model and procedure presented in the preceding paper. The activity of the solvent is expressed as a function of its concentration in the swollen network, and of the degree of cross‐linking. The maximum degree of swelling of the network in contact with the pure solvent is related to the degree of cross‐linking. The heat of interaction of the solvent with the network can be calculated from the temperature coefficient of maximum swelling. The theory leads to the conclusion that the swelling capacity should be diminished by the application of an external stress. Furthermore, the modulus of elasticity should decrease inversely with the cube root of the swelling volume.

Statistical mechanics of cross-linked polymer networks ii. swelling

A model is proposed for the structure of a cross‐linked network, such as exists in a vulcanized rubber, which is amenable to statistical treatment. Expressions are derived for the structural entropy of the network, and for the entropy change on deformation. The latter is in agreement with the relationship derived by Wall and others by a different treatment.

Statistical Mechanics of Cross‐Linked Polymer Networks I. Rubberlike Elasticity

Elongation of swollen vulcanized rubber, or other polymeric materials possessing random network structures, should increase the amount of liquid absorbed (dissolved) at equilibrium with an excess of the swelling agent. According to a previously published equation relating to the thermodynamics of stretching and swelling of rubber, the relative volume of the swollen rubber at equilibrium should equal the square root of the relative stretched length. Experiments with butyl rubber vulcanizates in xylene support these predictions of theory.

Effect of Deformation on the Swelling Capacity of Rubber

Polymeric molecules composed of long, primary valence chains can assume numerous configurations made possible by quasi-free rotation about single carbon to carbon bonds within the chain skeleton. The development of a statistical mechanical theory of chain configuration, baaed on the pioneering work of Eyring,' Guth and Mark2 and Kuhn3 has been particularly successful in explaining rubber-like elasticity of a number of substances composed of very long-chain molecules. In the undeformed state the chains assume configurations approximating closely to their most probable configuration. Deformation results in a displacement of chain configurations. Thus deformation is accompanied by a decrease in entropy, which is the major factor responsible for rubber-like elasticity. Another phenomenon closely related to elastic deformation is that of limited swelling of cross-linked, or vulcanized, high polymers in contact with solvents. The network structure is expanded by the dissolved solvent up to the point where the elastic forces in the chains of the network become counterbalanced by the tendency toward dilution by solvent. Various theories of chain configuration and t.heir application to the deduction of relations between elastic properties and structure will be reviewed in the course of the following discussion. Special attention will be devoted to the effects of low chain flexibility due to hindered rotation about single bonds of the chain. A new model for network polymer structures which provides an alternate procedure for deriving elastic characterktics will be described.

Statistical theory of chain configuration and physical properties of high polymers

Literature on the fundamental physios and chemistry of elastomers blends is limited, even though blends are employed commercially. Past research on individual elastomers is inadequate for a good understanding of blends. Properties of elastomers blends, unlike those of plastic blends, depend on vulcanization chemistry. The general problem is therefore one of understanding the nature and properties of elastomer blends in which complex chemical reactions have been superimposed on a complex physical state. The present paper is a preliminary examination of both of these aspects.

John Rehner

Papers

Statistical mechanics of cross-linked polymer networks ii. swelling

Statistical Mechanics of Cross‐Linked Polymer Networks I. Rubberlike Elasticity

Effect of Deformation on the Swelling Capacity of Rubber

Statistical theory of chain configuration and physical properties of high polymers

Heterogeneity and Crosslinking of Elastomer Blends. Investigations of Chlorobutyl with Highly Unsaturated Elastomers