Showing papers by "Nicholas A. Peppas published in 2008"
TL;DR: The hierarchical system of recognition in nature is based on interaction between the smallest elements in a matrix such as molecules and the cumulative interactions of larger parts such as the helices and sheets of proteins.
195 citations
TL;DR: This very first model to predict release from blend of PLGA and PCL was developed based on a heuristic approach and exhibited good prediction of the experimental data.
151 citations
TL;DR: It is concluded that the addition of the WGA on the microparticles produces a specific adhesion to carbohydrate-containing surfaces and that P(MAA-g-EG) WGA shows great promise as an oral insulin delivery system.
76 citations
TL;DR: Moisture absorption studies revealed that the hygroscopic nature of SBE(7)-beta-CD led to particle aggregation and a corresponding decrease in drug release rate for all samples, however, the samples prepared by melt extrusion were least affected by exposure to elevated humidity.
73 citations
TL;DR: The basis of recognitive delivery systems that would be able to recognize various biomarkers and respond to their high concentrations are examined and their main mechanisms and transducing action are identified.
71 citations
TL;DR: Experimental results indicate that tighter mesh-sized networks had increased affinity and capacity towards the glucose functionalized molecule as well as increased diffusional transport times, indicating the strong potential to load significantly higher amounts of therapeutic within intelligent carriers aswell as control and extend the rate of release via macromolecular structure.
Abstract: Molecular imprinting techniques have been developed for the preparation of biomimetic polymer networks that can recognize a general moiety, D-glucose, and the novel evaluation of loading and release of a larger molecule with glucose as an integral part of its structure [i.e., fluorescently tagged glucose (2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy-glucose) or 2-NBDG]. Poly(acrylamide-co-poly(ethylene glycol)dimethacrylate) networks with varying crosslinking monomer percentages (80, 67, and 30%) and crosslinker lengths (average number of ethylene glycol units of 1, 4, and 14) were prepared and characterized using a novel fluorescent microscopy technique, which allowed for microscale observation of the dynamic binding and release of 2-NBDG within the polymer film. Experimental results indicate that tighter mesh-sized networks had increased affinity and capacity towards the glucose functionalized molecule as well as increased diffusional transport times, indicating the strong potential to load significantly higher amounts of therapeutic within intelligent carriers as well as control and extend the rate of release via macromolecular structure.
46 citations
TL;DR: Results from confocal microscopy analysis of insulin transport in Caco-2 cells indicated that the primary route of transport was the paracellular pathway and that the transcellular component of the transport was insignificant.
31 citations
TL;DR: In this paper, a configurational biomimetic imprinting technique was used to determine the overall macroscopic properties of protein-imprinted gel, using a variety of tools.
Abstract: Using a configurational biomimetic imprinting technique, we prepared a family of molecularly imprinting polyacrylamide polymers with recognition for the template protein chicken egg white lysozyme in aqueous solution. We showed the formation of a network with specific recognitive sites for the template. To determine the overall macroscopic properties of protein-imprinted gel, we utilized a variety of tools. When gels were examined using scanning electron microscopy, definite morphological differences were observed between the CBIP polymers and the controls. Additionally, Fourier transform infrared spectroscopy determined that the presence of template had no effect upon the overall gel composition, whereas differential scanning calorimetry showed no significant change in the molecular weight between cross-links between CBIP polymers and nonimprinted polymers. Using these results, a theory of gel formation was proposed to try to elucidate gel formation in the presence of a macromolecule.
29 citations
TL;DR: Hydrogels comprised of poly(methacrylic acid) grafted with poly(ethylene glycol) (P(MAA-g-EG)) were characterized and examined for their potential as oral insulin carriers and induced a hypoglycemic effect and an increase in insulin levels, proving that insulin was still biologically active.
28 citations
04 Dec 2008
TL;DR: In this article, the authors present compositions, methods, and systems for the controlled delivery of an active agent within a polymeric network upon the binding of a molecule that decreases the structural integrity of the polymeric networks at one or more micro- or nanovacuoles.
Abstract: The present invention includes compositions, methods, systems for the controlled delivery of an active agent within a polymeric network upon the binding of a molecule that decreases the structural integrity of the polymeric network at one or more micro- or nanovacuoles.
25 citations
TL;DR: A mathematical model describing glucose-dependent pH swelling and insulin release is developed for pH-sensitive cationic hydrogels in which glucose oxidase and catalase have been immobilized and insulin imbibed.
Abstract: A mathematical model describing glucose-dependent pH swelling and insulin release is developed for pH-sensitive cationic hydrogels in which glucose oxidase and catalase have been immobilized and insulin imbibed. Glucose-based swelling and insulin release are simulated for intravenously injected particles at various design conditions. The effects of particle size, the number of injected particles, insulin loading, enzyme loading, monomer functional group loading and pKa, and hydrogel cross-linking ratio on insulin release and glucose sensitivity are investigated to optimally design the device for use. Increased insulin infusion is shown to result from increasing the number of circulating gels, increasing the collapsed particle size, or decreasing the cross-linking ratio of the system. Release duration is shown to be dependent only upon the particle size and the achievable diffusion coefficient of the system. Glucose sensitivity, as measured by gluconic acid production and by the system pH, is a function of...
TL;DR: A confocal microscopy imaging method was developed to determine the effect of microparticulate poly(methacrylic acid) grafted poly(ethylene glycol) (P(MAA-g-EG) hydrogel drug carriers on the integrity of claudin-1 and E-cadherin networks in Caco-2 monolayers.
Patent•
04 Dec 2008TL;DR: In this paper, the present invention includes compositions, methods, systems of making a composition that includes one or more active agents; a recognitive polymeric matrix; and a porosigen, wherein the composition comprises a porous recognitive, swellable hydrogel that dissociates under conditions of low water or humidity.
Abstract: The present invention includes compositions, methods, systems of making a composition that includes one or more active agent; a recognitive polymeric matrix; and a porosigen, wherein the composition comprises a porous recognitive, swellable hydrogel that dissociates under conditions of low water or humidity.
28 May 2008
TL;DR: In this article, an enzyme-substrate reaction that results in a pH change and a pH-sensitive polymer that responds to the change is described, which could lead to better control of blood glucose levels in diabetic patients.
Abstract: glucose levels, so as to mimic the natural response of the body. This could lead to better control of blood glucose levels in diabetic patients. This approach involves an enzyme–substrate reaction that results in a pH change and a pH-sensitive polymer that responds to the change. Glucose reacts with glucose oxidase (GOD) forming gluconic acid (GlucA) and, thus decreasing the pH of the environment. With the change in pH, the gel swells or collapses depending on the characteristics of the particular polymer of the system. Insulin is released from this system with the change in the size of the pores of the polymer. [3] In the last few years, extensive work has been carried out with poly(methacrylic acid) (PMAA), poly(ethylene glycol) (PEG), poly(diethylamino ethyl methacrylate) as well as more complex structures including complexation hydrogels of poly(methacrylic acid-g-ethylene glycol) [P(MAA-g-EG)]. Interpolymer complexes are formed in these hydrogels because of hydrogen bonding between the hydrogens of the carboxylic group of the PMAA and the oxygens on the ether groups of the PEG chains. At low pH values, there is sufficient protonation of the carboxylic acid groups causing complexes to form. This results in a collapse of the gel because of the increased hydrophobicity in the polymer network. At high pH values, complexes break as the carboxylic groups become ionized. This results in an expansion of the gel as electrostatic repulsion is produced within the network. In our specific hydrogel systems, the two species involved in the complexation are bound together in the same polymer. This allows for the reversible formation of complexes at appropriate conditions. Therefore, these materials allow for pH-sensitive solute permeation, a property that is important for drug release. [4] When incorporating P(MAA-g-EG) with GOD, a ‘‘squeezing gel’’ is formed. At high concentrations of glucose, the GODcatalyzed reaction of glucose produces GlucA, resulting in a decrease in the pH of the environment around the gel. Glucose-sensitive hydrogels collapse in response to the decrease in pH. Thus, insulin could be squeezed out of the network. There are several important parameters controlling the behavior of glucose-responsive hydrogel system. The equilibrium and dynamic degrees of swelling are important parameters for calculating network mesh size and molecular weight between cross-links under different experimental conditions. The permeability characteristics of the gels are also important when considering the system for insulin release.
TL;DR: Simulations demonstrate limitations in the range of swelling and contraction of hydrogels in a physiological environment due to the Donnan equilibrium effect and the evaluation of ionic hydrogel membrane macrosystems prompts the consideration of detected pros and cons.
Abstract: Hydrogels provide the multifunctionality of smart materials and the applicability to medical regulatory systems. Hydrogel membranes that incorporate glucose oxidase for the closed loop treatment of type 1 diabetes mellitus are characterized and modeled. The Sorensen compartmental model is extended to represent the treatment system of a diabetic patient. The performance of the system closed by a hydrogel-based device is explored and compared to the dynamic behavior of a conventional scheme with an explicit controller element. Anionic and cationic hydrogels are discussed for insulin delivery application. Simulations demonstrate limitations in the range of swelling and contraction of hydrogels in a physiological environment due to the Donnan equilibrium effect. Results show the reduction of peak glucose levels and a basal insulin delivery from a hydrogel membrane system. The evaluation of ionic hydrogel membrane macrosystems prompts the consideration of detected pros and cons using different hydrogels, structures and scales. © 2008 American Institute of Chemical Engineers AIChE J, 2008
TL;DR: A pharmacokinetic model is proposed to describe the glucoregulatory process that describes the dynamics of glucose, amino acids, and fatty acids, as well as both the hormonal actions and dynamics of insulin, glucagon, epinephrine, and glucagon-like peptide-one.
TL;DR: Improved estimation could result in more accurate simulations for use in glucose control system design and the use of user-defined gradients and Hessian matrices results in more accurately parameter estimations for insulin transport models.
Abstract: Background: The use of patient models describing the dynamics of glucose, insulin, and possibly other metabolic species associated with glucose regulation allows diabetes researchers to gain insights regarding novel therapies via simulation. However, such models are only useful when model parameters are effectively estimated with patient data. Methods: The use of least squares to effectively estimate model parameters from simulation data was investigated by observing factors that influence the accuracy of estimates for the model parameters from a data set generated using a model with known parameters. An intravenous insulin pharmacokinetic model was used to generate the insulin response of a patient with type 1 diabetes mellitus to a series of step changes in the insulin infusion rate from an external insulin pump. The effects of using user-defined gradient and Hessian calculations on both parameter estimations and the 95% confidence limits of the estimated parameter sets were investigated. Resul...