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Showing papers by "Nicholas A. Peppas published in 2000"


Journal ArticleDOI
TL;DR: The aim of this article is to present a concise review on the applications of hydrogels in the pharmaceutical field, hydrogel characterization and analysis of drug release from such devices.

3,484 citations


Book ChapterDOI
TL;DR: In this article, a review of previous work in the development of freezing and thawing processes focusing on the implications of such materials for a variety of applications is presented, and future directions involving the further development of freeze/thawed PVA hydrogels are addressed.
Abstract: Poly(vinyl alcohol) (PVA) is a polymer of great interest because of its many desirable characteristics specifically for various pharmaceutical and biomedical applications. The crystalline nature of PVA has been of specific interest particularly for physically cross-linked hydrogels prepared by repeated cycles of freezing and thawing. This review includes details on the structure and properties of PVA, the synthesis of its hydrogels, the crystallization of PVA, as well as its applications. An analysis of previous work in the development of freezing and thawing processes is presented focusing on the implications of such materials for a variety of applications. PVA blends that have been developed with enhanced properties for specific applications will also be discussed briefly. Finally, the future directions involving the further development of freeze/thawed PVA hydrogels are addressed.

1,284 citations


Journal ArticleDOI
TL;DR: This review discusses the molecular structure, dynamic behavior, and structural modifications of hydrogels as well as the various applications of these biohydrogels.
Abstract: ▪ Abstract Hydrogels are cross-linked hydrophilic polymers that can imbibe water or biological fluids. Their biomedical and pharmaceutical applications include a very wide range of systems and processes that utilize several molecular design characteristics. This review discusses the molecular structure, dynamic behavior, and structural modifications of hydrogels as well as the various applications of these biohydrogels. Recent advances in the preparation of three-dimensional structures with exact chain conformations, as well as tethering of functional groups, allow for the preparation of promising new hydrogels. Meanwhile, intelligent biohydrogels with pH- or temperature-sensitivity continue to be important materials in medical applications.

955 citations


Journal ArticleDOI
TL;DR: The structure and morphology of polyvinyl alcohol (PVA) gels prepared by repeated cycles of 8 h freezing at −20 °C and 4 h thawing at +25 °C were examined in this paper.
Abstract: The structure and morphology of poly(vinyl alcohol) (PVA) gels prepared by repeated cycles of 8 h freezing at −20 °C and 4 h thawing at +25 °C were examined. Long-term morphological changes of such gels were determined upon swelling in water at 37 °C for 6 months. The preparation conditions were examined by varying such parameters as the number of freezing and thawing cycles, the concentration of aqueous solution, and the PVA molecular weight. The overall structure and stability were examined in terms of water content, fractional PVA dissolution, degree of crystallinity, and crystal size distribution. An increase in the number of freezing and thawing cycles served to reinforce existing crystals within the structure. Increased initial concentrations of aqueous PVA solutions resulted in hydrogels that contained initially higher crystallinity and added stability upon swelling. An increase in the PVA molecular weight resulted in crystals of higher lamellar thickness and a broadening of the crystal size distri...

674 citations


Journal ArticleDOI
TL;DR: In this paper, a sequential UV polymerization method was used to construct an interpenetrating polymeric network (IPN) composed of the temperature-sensitive poly(N-isopropylacrylamide) (PNIPAAm) and the pH sensitive poly(methacrylic acid) (PMAA), which exhibited a combined pH and temperature-sensitivity at a temperature range of 31−32 °C and a pH value of approximately 5.5.
Abstract: Hydrogels of an interpenetrating polymeric network (IPN) composed of the temperature-sensitive poly(N-isopropylacrylamide) (PNIPAAm) and the pH-sensitive poly(methacrylic acid) (PMAA) were prepared by a sequential UV polymerization method. The IPN hydrogels were characterized for their temperature- and pH-responsive behavior by equilibrium swelling studies, oscillatory swelling studies, and differential scanning calorimetry. The permeability of these IPNs has been investigated under various pH and temperature conditions. The results showed that these hydrogels exhibited a combined pH- and temperature-sensitivity at a temperature range of 31−32 °C and a pH value of approximately 5.5. Permeation study results indicate a significant size exclusion behavior while model drugs with different sizes permeate through the IPN membranes. The permeability of the IPN membrane can be significantly affected by varying the pH and temperature conditions.

478 citations


Journal ArticleDOI
TL;DR: Gel-layer behaviour, front movement and release are described to show the dependence of the release kinetics on the swelling behaviour of the system and in vivo behaviour of matrix systems.

402 citations


Journal ArticleDOI
TL;DR: In this paper, a robust H∞ controller was developed to deliver insulin via a mechanical pump in Type I diabetic patients, and the controller was evaluated in terms of its ability to track a normoglycemic set point (81.1 mg/dL) in response to a 50 g meal disturbance.
Abstract: A robust H∞ controller was developed to deliver insulin via a mechanical pump in Type I diabetic patients. A fundamental nonlinear diabetic patient model was linearized and then reduced to a third-order linear form for controller synthesis. Uncertainty in the nonlinear model was characterized by up to ± 40% variation in eight physiological parameters. A sensitivity analysis identified the three-parameter set having the most significant effect on glucose and insulin dynamics over the frequency range of interest ω = [0.002, 0.2] (rad/min). This uncertainty was represented in the frequency domain and incorporated in the controller design. Controller performance was assessed in terms of its ability to track a normoglycemic set point (81.1 mg/dL) in response to a 50 g meal disturbance. In the nominal continuous-time case, the controller maintained glucose concentrations within ± 3.3 mg/dL of set point. A controller tuned to accommodate uncertainty yielded a maximum deviation of 17.6 mg/dL for the worst-case parameter variation.

344 citations


Journal ArticleDOI
TL;DR: Experimental results indicate that the chain interpenetration is a strong function of the PEG molecular weight, the polymer swelling ratio and the mucosa composition.

341 citations


Journal ArticleDOI
TL;DR: The water Swelling and drug diffusion from initially hydrophilic, glassy polymer matrices were modeled using concentration-dependent diffusion equations for water and drug using an appropriate boundary condition incorporating a relaxation-dependent Deborah number.

337 citations


Journal ArticleDOI
TL;DR: An improved design model is developed that can be used to predict accurately the required composition and dimensions of drug-loaded hydrophilic matrices in order to achieve desired release profiles, thus facilitating the development of new pharmaceutical products.
Abstract: Purpose. The aims of this study were (i) to elucidate the transport mechanisms involved in drug release from hydrophilic matrices; and (ii) to develop an improved mathematical model allowing quantitative predictions of the resulting release kinetics. Methods. Our previously presented model has been substantially modified, by adding: (i) inhomogeneous swelling; (ii) poorly water-soluble drugs; and (iii) high initial drug loadings. The validity of the improved model has been tested experimentally using hydroxypropyl methylcellulose (HPMC)-matrices, containing either a poorly or a freely water-soluble drug (theophylline or chlorpheniramine maleate) at various initial loadings in phosphate buffer pH 7.4 and 0.1 N HCl, respectively. Results. By overcoming the assumption of homogeneous swelling we show that the agreement between theory and experiment could be significantly improved. Among others, the model could describe quantitatively even the very complex effect on the resulting relative release rates (first slowing down, then accelerating drug release) observed when increasing the initial loading of poorly water-soluble drugs. Conclusions. The practical benefit of this work is an improved design model that can be used to predict accurately the required composition and dimensions of drug-loaded hydrophilic matrices in order to achieve desired release profiles, thus facilitating the development of new pharmaceutical products.

217 citations


Journal ArticleDOI
TL;DR: The generation of gluconic acid as a result of the reaction of glucose with oxygen was investigated as a function of polymer parameters, such as crosslinking ratio and enzyme loading.

Journal ArticleDOI
01 May 2000-Polymer
TL;DR: In this article, a copolymerization of diethylaminoethyl methacrylate (DEAEM), poly(ethylene glycol) monomethacrylated (PEGMA) and functionalized glucose oxidase (GOD) and catalase was used as the crosslinking agent.

Journal ArticleDOI
TL;DR: Both, theoretical and experimental data showed that a broad spectrum of drug release patterns can be achieved by varying the size and shape of the tablet, thus significantly facilitating the development of new pharmaceutical products.

Journal ArticleDOI
TL;DR: Laminates containing gel layers prepared after 3 or 5 cycles were successfully prepared with good stability over a 6 month swelling period and could be used to achieve zero-order release behavior in novel, freeze/thawed PVA laminates.

Journal ArticleDOI
01 Aug 2000-Polymer
TL;DR: In this paper, a model was developed to describe the overall dissolution kinetics of semicrystalline PVA gels prepared by freezing and thawing techniques, and the dissolution process was described as a three-step mechanism: detachment-, diffusion-, and disentanglement-controlled dissolution.

Journal ArticleDOI
TL;DR: The aim of this study was to develop new multi-layer matrix tablets to achieve bimodal drug release profiles (fast release/slow release/fast release) and Hydroxypropyl methylcellulose acetate succinate (HPMCAS) was chosen as a matrix former, because it is water-insoluble at low, and water-soluble at high pH values.

Journal ArticleDOI
TL;DR: It was found that longer graft lengths were responsible for increasing the effect of relaxation of the swelling of the network, and faster response could be obtained from smaller particles.

Journal ArticleDOI
TL;DR: In this article, cellular polyvinyl alcohol (PVA) hydrogels that exhibit enhanced swelling kinetics from an initial dry state were prepared by freezing and thawing techniques in the presence of NaCl.
Abstract: Cellular poly(vinyl alcohol) (PVA) hydrogels that exhibit enhanced swelling kinetics from an initial dry state were prepared by freezing and thawing techniques in the presence of NaCl. Gels that were dried immediately after preparation demonstrated a dual-sorption effect upon swelling. Gels that were exposed to a 10-day washing period to remove NaCl and excess PVA chains before drying showed an increased initial rate of swelling and overall water content. Freeze/thawed, cellular PVA gels showed overall enhanced swelling with increased mechanical strength over traditional gels prepared by chemical or irradiative crosslinking techniques. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 2075–2079, 2000

Journal ArticleDOI
TL;DR: Oil-based and polymer-based delivery systems are discussed, designed to protect the polypeptide from the biological barriers that each delivery route imposes, that are used in salmon calcitonin treatment.

Journal ArticleDOI
01 Jan 2000-Polymer
TL;DR: In this article, the degree of interpolymer complexation in poly(methacrylic acid-g-ethylene glycol) graft copolymer networks was determined as a function of copolymers composition, PEG graft chain molecular weight and environmental pH.

Journal ArticleDOI
TL;DR: In this article, a kinetic gelation model was developed that incorporates the kinetics of a living/controlled radical polymerization, and the model predicts the formation of more monodisperse linear polymers in the presence of an iniferter and a reversible termination.
Abstract: A kinetic gelation model has been developed that incorporates the kinetics of a living/controlled radical polymerization. Specifically, the kinetics of an iniferter polymerization were implemented in the model to determine the effect of the kinetics on the polymer structure. In particular, the replacement of the termination step with a reversible termination was examined. The model predicts the formation of more monodisperse linear polymers in the presence of an iniferter and a reversible termination reaction. When termination by combination is allowed to occur, the polydispersity increases. For cross-linking reactions, it was concluded that the iniferter only had an effect on reactions with small amounts of cross-linking agent, resulting in a delay in the gel point and a more heterogeneous structure. When the amount of cross-linking agent is increased, there is no difference in the network structure obtained by a cross-linking reaction with an iniferter versus a cross-linking reaction with the classical ...

Journal ArticleDOI
TL;DR: In this paper, solid-state, nuclear magnetic resonance nuclear Overhauser enhancement (NOE) experiments were performed to detect the molecular level complexation between PMAA and deuterated PEG in copolymer blends and crosslinked networks.
Abstract: Copolymer networks of poly(methacrylic acid) (PMAA) and poly(ethylene glycol) (PEG) exhibit large changes in their swelling behavior over a narrow pH range due to the reversible formation/dissociation of interpolymer complexes between the polymer chains. Interpolymer complexation occurs in copolymer gels of PMAA and PEG due to hydrogen bonding between protonated acid groups and the ether groups of the PEG. Because of their nature, these gels have been identified for use as delivery vehicles for macromolecular drugs. In this work, solid-state, nuclear magnetic resonance nuclear Overhauser enhancement (NOE) experiments were performed to detect the molecular level complexation between PMAA and deuterated PEG in copolymer blends and crosslinked networks. For gels swollen in acidic media at room temperature or at 37°C, strong enhancements were detected in the 13 C resonance of the PEG carbons. The NOE was generated due to energy transfer between the rapidly rotating methyl group protons and the deuterated PEG carbons. The presence of the NOE was indicative of close packing of the polymer chains and was evidence of the presence of the intermacromolecular complexes. In basic solutions, no NOE was detected in the PEG, as the complexes were dissociated and the chains were separated in space.


Proceedings ArticleDOI
30 Jun 2000
TL;DR: In this article, a block copolymerization of monomers using UV free-radial polymerization was proposed to create patterns on the films by applying a mask and selectively irradiating the surface.
Abstract: We have developed novel techniques for the preparation of micropatterned structures from thin films prepared by the block copolymerization of monomers using UV free-radial polymerizations. The process involves polymerizing the first monomer layer in the presence of an iniferter (initator-transfer agent-terminator) with a dithiocarbamate group to make a photosensitive polymer. Upon application of the second monomer layer on the first polymer layer and irradiation, a copolymer is formed between the two layers. Patterns are created on the films by applying a mask and selectively irradiating the surface. We have successfully polymerized poy (ethylene glycol) (PEG) onto a highly crosslinked material of poly(ethylene glycol) dimethacrylate. Various patterns have been created to determine the precision that can be achieved with this method. Preliminary results show that the patterns in the second monomer layer can be from 5 micrometers to 100 micrometers thick, with feature size as small as 5 micrometers , allowing the use of this material to high aspect ratio structures for micro-fluidics. In addition, applications of this type of material are also in bioMEMS, biomaterials, and biosensors for the selective adhesion of cells and proteins.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.





01 Jan 2000
TL;DR: In this paper, the authors modeled the water swelling and drug diffusion from initially hydrophilic, glassy polymer matrices using concentration-dependent diffusion equations for water and drug, and solved these equations with an appropriate boundary condition incorporating a relaxation-dependent Deborah number.
Abstract: The water swelling and drug diffusion from initially hydrophilic, glassy polymer matrices were modeled using concentration-dependent diffusion equations for water and drug. The transport equation for water incorporated a relaxation-dependent mechanism. These equations were solved with an appropriate boundary condition incorporating a relaxation-dependent Deborah number. Experimental results from drug release from PVA and PHEMA samples were used to determine the validity of the model. q 2000 Elsevier Science B.V. All rights reserved.