Biomedical subjects

Nicholas A Peppas

Publications and source records attributed to Nicholas A Peppas.

42 records · Page 3Linked to original sources

PubMed2002

Molecular imprinting within hydrogels.

Hydrogels have been used primarily in the pharmaceutical field as carriers for delivery of various drugs, peptides and proteins. These systems have included stimuli-responsive gels that exhibit reversible swelling behavior and hence can show modulated release in response to external stimuli such as pH, temperature, ionic strength, electric field, or specific analyte concentration gradients. The focus of this article is to review molecular imprinting within hydrogels and discuss recent efforts on analyte-responsive intelligent gels, specifically suggesting the possibility of utilizing molecular imprinting strategies to impart analyte specificity and responsiveness within these systems. Molecular imprinting is an emerging field that produces precise chemical architecture that can bind analytes and differentiate between similar molecules with enantiomeric resolution. On the forefront of imprinting gel systems are intelligent, stimuli-sensitive imprinted gels that modify their swelling behavior and in turn modulate their analyte binding abilities. We discuss the challenges creating an imprinting effect in hydrogels and the possibilities of using molecularly imprinted mechanisms within controlled release gels.

Chemistry, Pharmaceutical↗

PubMed2002

Polymers and gels as molecular recognition agents.

Synthetic polymers and gels capable of molecular recognition are very useful in designing novel intelligent biomaterials. In this article we review the recent progress in both theoretical and experimental studies toward making heteropolymers and gels with biomimetic properties, specifically in relation to protein recognition. Knowledge obtained from protein-folding studies sheds much light on our understanding of the heteropolymer behavior. Consequently, it is possible to design synthetic heteropolymers with specific structure that can fold into unique conformations, form receptor-like cavities and recognize specific target molecules. Recent studies towards simplifying the requirement for the heteropolymer structures and the polymerization procedures are reviewed. Intelligent polymer gels can be designed with new and interesting characteristics of molecular imprinting. The results are encouraging for further investigation and design of synthetic gels with programmable collapsed structure might be achieved.

Drug Design↗

PubMed2002

Network structure of cellulose ethers used in pharmaceutical applications during swelling and at equilibrium.

PURPOSE: The purpose of this work was to investigate the swelling behavior of four cellulose ethers that differ in their type and degree of substitution and to elucidate the network structure of the swollen matrices under dynamic and equilibrium conditions. METHODS: Dynamic vapor sorption was performed to assess the ability of polymer chains and water molecules to interact. Dynamic and equilibrium swelling studies were performed to calculate molecular parameters of swollen polymers using the Flory-Rehner theory. RESULTS: We determined the volume-swelling ratio of the polymer matrices and observed that it was dependent on their hydrophilicity. We determined molecular parameters that characterize the swollen hydrogels of cellulose derivatives, such as the polymer volume fraction in the swollen state, u2,S, the effective molecular weight of the polymer chain between physical entanglements, Me, the number of repeating units between two entanglements, u, and the number of entanglements per chain, e. The Me of the cellulose derivatives studied varied significantly depending on the type of cellulose ether and on the swelling time. CONCLUSIONS: The order of mesh size, an important parameter for predicting drug diffusion and release, taking into account all determined parameters, is: hydroxypropyl cellulose < hydroxyethyl cellulose < hydroxypropyl methyl cellulose K100M < hydroxypropyl methyl cellulose K4M.

Cellulose↗

PubMed2002

Synthesis and characterization of pH-sensitive glycopolymers for oral drug delivery systems.

pH-sensitive hydrogels are suitable candidates for oral delivery of therapeutic peptides and proteins, due to their ability to respond to environmental pH changes. New pH-sensitive glycopolymers have been developed by free-radical photopolymerization of methacrylic acid and 2-methacryloxyethyl glucoside, using tetra(ethylene glycol) dimethacrylate as a cross-linking agent. To determine the suitability of these hydrogels as carriers for oral drug delivery devices, their swelling behavior was investigated as a function of the pH and copolymer compositions, and various structural parameters such as the number-average molecular weight between cross-links, Mc, the mesh size, xi, and the cross-linking density, rho(x), were calculated. The transition between the swollen and the collapsed states of these hydrogels was at a pH of 5. The swelling ratios of the hydrogels increased at pH values above 5. The mesh sizes of the hydrogels were between 18 and 35 A in the collapsed state (at pH 2.2) and between 70 and 111 A in the swollen state (at pH 7.0). Finally, as the cross-linking ratio of the copolymer increased, the swelling ratio of the hydrogels decreased at both pH 2.2 and 7.0.

Absorption↗

PubMedDate not supplied

Synthesis and characterization of insulin-transferrin conjugates.

Receptor-mediated endocytosis can be exploited for improving the transcellular delivery of therapeutic proteins. Insulin conjugated to transferrin by forming disulfide bonds has been shown to improve insulin oral bioavailability in diabetic rats. We are developing a combination strategy involving complexation hydrogels as delivery vehicles for insulin-transferrin conjugates. The complexation hydrogels developed in our laboratory have been shown to be promising carriers for oral delivery of proteins and peptides. Integrating the strategies based on the complexation hydrogels and insulin-transferrin conjugates may prove to be a novel approach for oral delivery of insulin and other therapeutic proteins. In this work, electrospray ionization mass spectrometry (ESI-MS) was used to study the modification of insulin during its reaction with transferrin. The stability of the conjugated insulin to enzymatic degradation was also studied. ESI-MS studies confirmed the site-specific modifications of insulin. The transferrin conjugation of insulin was also shown to increase the stability of insulin to enzymatic degradation.

Amines↗

PubMedDate not supplied

pH-Sensitive hydrogels as gastrointestinal tract absorption enhancers: transport mechanisms of salmon calcitonin and other model molecules using the Caco-2 cell model.

The main interest of this work was the investigation of the transport mechanisms of salmon calcitonin through the epithelial cell monolayer in the presence and absence of pH-sensitive hydrogel nanospheres composed of poly(methacrylic acid-grafted-poly(ethylene glycol)) (PMAA-g-EG). For this purpose, a gastrointestinal cell culture model, the Caco-2 cell line, was employed. The transport of other macromolecules such as fluorescein sodium, fluorescein isothiocyanate dextran, and (14)C-mannitol were also investigated and compared. Transport experiments were conducted in the apical-to-basolateral direction at 37 and 5 degrees C and from the basolateral-to-apical direction at 37 degrees C. Results revealed that the presence of P(MAA-g-EG) nanospheres increased the transport of paracellularly transported molecules such as (14)C-mannitol and fluorescein isothiocyanate dextran when compared to controls. Fluorescein sodium salt solutions were investigated as an actively transported molecule. The transport of fluorescein was affected by the concentration of PEG chains in the structure. Salmon calcitonin transport was enhanced in the presence of the nanospheres. The comparison of the transport behavior of dextran and calcitonin revealed that the main transport mechanism for salmon calcitonin through epithelial cell monolayers is predominantly paracellular.

Biological Transport↗