Donald Eagland

Poly(vinyl alcohol) Hydrogel as a Biocompatible Viscoelastic Mimetic for Articular Cartilage

The prevalence of suboptimal outcome for surgical interventions in the treatment of full‐thickness articular cartilage damage suggests that there is scope for a materials‐based strategy to deliver a more durable repair. Given that the superficial layer of articular cartilage creates and sustains the tribological function of synovial joints, it is logical that candidate materials should have surface viscoelastic properties that mimic native articular cartilage. The present paper describes force spectroscopy analysis by nano‐indentation to measure the elastic modulus of the surface of a novel poly(vinyl alcohol) hydrogel with therapeutic potential as a joint implant. More than 1 order of magnitude decrease in the elastic modulus was detected after adsorption of a hyaluronic acid layer onto the hydrogel, bringing it very close to previously reported values for articular cartilage. Covalent derivatization of the hydrogel surface with fibronectin facilitated the adhesion and growth of cultured rat tibial condyle chondrocytes as evidenced morphologically and by the observance of metachromatic staining with toluidine blue dye. The present results indicate that hydrogel materials with potential therapeutic benefit for injured and diseased joints can be engineered with surfaces with biomechanical properties similar to those of native tissue and are accepted as such by their constituent cell type.

Complexation between polyoxyethylene and polymethacrylic acid—the importance of the molar mass of polyoxyethylene

Abstract The effect of the molar mass of polyoxyethylene, POE, upon the mechanism of complexation with polymethacrylic acid, PMAA, has been examined, using pH, density, calorimetric and cloud point studies. Complexation has been found to occur, even for POE of molar mass as low as 200, further, the mechanism appears to be more complex than a simple 1:1 base mole pairing of oxyethylene units (OE) with methacrylic acid units (MAA) by a hydrogen bond mechanism. When the molar mass of POE is

The influence of hydration upon the potential at the shear plane (zeta potential) of a hydrophobic surface in the presence of various electrolytes

Abstract Evidence is presented from the literature for the importance of water structure for the stability of colloidal systems having hydrophilic character and the confused nature of the evidence for the involvement of hydration of hydrophobic surfaces. Streaming potential results at a polyvinylacetate/water interface in the presence of LiCl, LiBr, LiI, Li 2 SO 4 , NaCl, KCl, CsCl, Me 4 NCl, Et 4 NCl, and Bu 4 NCl are presented; the data suggest a cation dependent yield stress within the liquid contained in the diaphragm pores. Together with concomitant surface conductance determinations these results gave values of electrokinetic potential which indicated strong specific anion adsorption at the apolar interface which was also observed in the case of Cs + , K + , and the tetraalkylammonium ions; no specific adsorption was observed in the case of Li + and Na + . The evidence obtained is used to support a possible explanation of the confusion with regard to the importance of hydration for the stability of hydrophobic sols.

Droplet aerodynamics, cellular uptake, and efficacy of a nebulizable corticosteroid nanosuspension are superior to a micronized dosage form

Inhaled corticosteroids are considered to be an effective prophylactic against the morbid symptoms of several lung diseases, but scope remains for improvement in drug delivery technology to benefit bioavailability and treatment compliance. To ascertain whether dosage form might influence bioavailability, the emission characteristics and efficacy of a nanoparticulate budesonide formulation (Nanagel®) were compared with those of a proprietary micronized suspension (Pulmicort®) when delivered as a nebulized aerosol to human airway epithelial cells in a culture model. Having the visual appearance of a clear solution, Nanagel® was delivered by both jet and vibrating mesh nebulizers as an increased fine particle fraction and with a smaller mass median aerodynamic diameter (MMAD) compared to the micronized suspension. Quantitative high performance liquid chromatography (HPLC) analysis of cultured epithelia one hour after treatment with Nanagel® revealed a significantly greater cellular accumulation of budesonide when compared with Pulmicort® for an equivalent dose, a differential which persisted 24 and 48 h later. A quantitative in vitro assay measuring the activity of enzymes involved in superoxide production revealed that stressed HaCaT cells (a long‐lived, spontaneously immortalized human keratinocyte line) treated with Nanagel® continued to show significantly greater attenuation of inflammatory response compared with Pulmicort®‐treated cells 24 h after the application of an equivalent budesonide dose. The present in vitro findings suggest that formulation of inhalable drugs such as budesonide as aerosolized nanoparticulate, rather than microparticulate, suspensions can enhance bioavailability with concomitant improvements in efficacy.

INFLUENCE OF COMPOSITION AND SEGMENT DISTRIBUTION UPON LOWER CRITICAL DEMIXING OF AQUEOUS POLY(VINYL ALCOHOL-STAT-VINYL ACETATE) SOLUTIONS

Abstract Cloud point data are presented for a series of 2% w/v solutions of poly(vinyl alcohol- stat -vinyl acetate) copolymers in water and a series of 0.15 M electrolyte solutions; the copolymers were of various compositions and segment length distributions. A relationship has been found showing that the relative sizes of the hydroxyl and acetate sequences, rather than their relative amounts, are the dominant factors in the determination of the lower critical demixing behaviour of this important polymer.

Factors influencing the aqueous solution behaviour of vinyl alcohol with vinyl acetate copolymers

Abstract Variations, as a function of temperature, are reported in the magnitude of values for the partial molal volume, partial molal expansibility, flowing volume and surface pressure for dilute solutions of a series of poly(vinyl alcohol-co-vinyl acetate) copolymers of various vinyl acetate contents and acetate sequence length. The temperature range investigated, from 5° to 30°, showed that, for all the examples examined, a general behaviour pattern was observed, indicating the predominance of hydrophilic interactions at temperatures below approximately 10°, with hydrophobic interactions predominating between 10° and 20°. The variations can be related to the detailed microstructure of the polymer backbone.

The volumetric behaviour of poly(vinyl alcohol) in aqueous solution

High-precision density measurements of aqueous solutions of a narrow molecular mass fraction of poly(vinyl alcohol) prepared by 80% alcoholysis of poly(vinyl acetate), over an extended range of concentration and temperature, have revealed a complex pattern of solution behaviour. The concentration dependence of the partial molal volume and apparent molal expansibility indicate that two processes occur in solution; a conformational change at low concentrations (ca. 0.05% w/w) and an aggregation at higher concentrations (ca. 0.2% w/w). The concentration at which these processes occur varies with temperature showing a minimum in the region 14–18 °C. The volumetric data presented suggest that the temperature dependence of these two processes is a function of the solvent–solvent interactions and the minimum at 14–18 °C reflects a critical region for water over this temperature range.

The rheological properties of concentrated polymer dispersions: I. The effects of concentration, particle size, and size distribution upon the shear dependence of viscosity

Abstract Measurements of viscosity have been obtained upon homogenized and unhomogenized polyvinyl acetate dispersions of differing sizes and size distributions. The measurements were obtained at shear rates ranging from 1 sec−1 to 2600 sec−1 for dispersion volume fractions of approximately 0.2 up to 0.5. The electrolyte content of the dispersions was held constant at 0.017 M. The data were analyzed on the basis of a three-component Eyring model for viscosity and the associated molecular parameters were obtained. The results obtained for the unhomogenized dispersions indicate the considerable errors in the derived values which may arise owing to the presence of coarse agglomerates of particles. The data for the homogenized dispersions illustrate a consistent trend in the derived parameters, showing that the relaxation time of the first non-Newtonian component is independent of the concentration and increases with increasing particle size. The relaxation time of the second non-Newtonian component exhibits a strong concentration dependence, decreasing rapidly with decreasing concentration and decreasing with increasing particle size. The Newtonian component ηo — η∞ and ηo — ηo for the homogenized dispersions show a linear dependence on concentration as suggested by the Mooney equation log e n re1 = k 1 k 2 φ/ (1 − k 2 φ) . The values of the associated particle-crowding factor k2 for the three parameters indicate that the second non-Newtonian flow unit which predominates at low rates of shear is associated with very marked particle interaction.

Rheological and densitometric studies of poly(propylene oxide)–water mixtures over a range of temperatures

Rheological and densitometric data are reported for aqueous solutions of poly(propylene oxide), molar mass 400 (PPO 400), over the concentration range 0–1 weight fraction and a temperature range 4.8–55 °C. Negative excess partial specific volumes were found, which varied as a function of temperature and concentration of PPO and which were found to correlate with the viscoelastic behaviour of the solutions. The PPO molecule, in the pure phase, was found to undergo a change of conformation at 30 °C.

Temperature-dependent studies of liquid surface tensions and works of adhesion for an eicosane surface

Abstract The surface tensions of water, glycerol, formamide, methylene iodide, 1-bromonaphthalene, 1-methylnaphthalene, benzaldehyde, and hydrazine hydrate have been determined over the temperature range 5 to 30°C; contact angle measurements of these liquids on an eicosane surface, over a similar temperature range, have also been determined. Polar and dispersion contributions to the surface tensions of the liquids have been determined and compared, where possible, with standard literature values. Values of enthalpy and entropy of adhesion of the liquids for the eicosane surface, as a function of temperature, appear to show a correlation with the temperature dependence of the dispersion force contribution to the surface tensions of the liquids.