FT-IR imaging spectroscopy is well suited for studying dynamic processes occurring in multi-component systems. Each component is resolved spatially based on the spectral response at each detector element. Additionally, the sequential collection of images tracks the movement of each component over time. In this study, the delivery characteristics of the drug, testosterone, suspended in a poly(ethylene oxide) (PEO) matrix was observed using this technique. Drug release occurred as the hydrophilic, erodible polymer underwent controlled dissolution, exposing the drug to the aqueous environment. The subsequent conversion of the drug into the therapeutic aqueous form completed the delivery process. Qualitative evaluation of the false color composite infrared images led to the elucidation of two distinct delivery mechanisms, dependent on the degree of drug loading. The spatially embedded spectral features led to the quantification of the drug release rates as well as the rates of polymer dissolution. The rates for both polymer dissolution and drug release were evaluated using well-established models. Additionally, the homogeneity of the drug dispersion for different loadings was characterized. The roles of chemical interactions across the solvent interface of species were also investigated. Changes in each component from the bulk to the solvated region were investigated, revealing changes in concentration and polymer orientation as well as inter-species interactions.

Gene therapy is an attractive strategy for the durable treatment of human osteoarthritis (OA), a gradual, irreversible joint disease. Gene carriers based on the small human adeno-associated virus (AAV) exhibit major efficacy in modifying damaged human articular cartilage in situ over extended periods of time. Yet, clinical application of recombinant AAV (rAAV) vectors remains complicated by the presence of neutralizing antibodies against viral capsid elements in a majority of patients. The goal of this study was to evaluate the feasibility of delivering rAAV vectors to human OA chondrocytes in vitro and in an experimental model of osteochondral defect via polymeric micelles to protect gene transfer from experimental neutralization. Interaction of rAAV with micelles of linear (poloxamer PF68) or X-shaped (poloxamine T908) poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) copolymers (PEO-PPO-PEO micelles) was characterized by means of isothermal titration calorimetry. Micelle encapsulation allowed an increase in both the stability and bioactivity of rAAV vectors and promoted higher levels of safe transgene (lacZ) expression both in vitro and in experimental osteochondral defects compared with that of free vector treatment without detrimental effects on the biological activity of the cells or their phenotype. Remarkably, protection against antibody neutralization was also afforded when delivering rAAV via PEO-PPO-PEO micelles in all systems evaluated, especially when using T908. Altogether, these findings show the potential of PEO-PPO-PEO micelles as effective tools to improve current gene-based treatments for human OA.

Polyether-polyester segmented block copolymers (Polyactive) on the basis of polybutylene terephthalate (PBT) and polyethylene oxide (PEO) were mechanically tested. Tensile strength and modulus of elasticity in compressive and tensile deformation were recorded according to ASTM standards. These tests were done in vitro under dry and wet conditions, and after 3, 9 and 25 wk subcutaneous implantation of these materials in goats. Strength and modulus of elasticity were higher with increased contents of PBT in the copolymers. After water uptake, the polymer displayed a lower strength and stiffness. Disintegration of the materials with 70% PEO content and dumb-bell shape was noted at 3 wk. Disintegration of the cylinders of the same material was seen after 25 wk implantation. Of the materials with 60% PEO content, only four of the five dumb-bells had disintegrated after 25 wk implantation. The in vivo test results of all other implants did not show a clinically relevant decrease of strength and stiffness with time after implantation of the copolymers in the goats. Mechanical behavior of the various copolymers seemed mainly determined by the amount and integrity of the PBT phase.

Osteoarthritis is one of the most economically important diseases facing equine practitioners. The loss of use associated with joint disease is a leading problem in the equine industry. Although osteoarthritis in all species is believed to be a multifactorial disease that is not well understood, significant advances are being made. This article presents areas of research that are relatively well developed but have not made it to commercialization or routine clinical practice and looks at new applications being investigated for peo-ple that may have an equine application.

The purpose of this study was to design an in vitro experiment that can assess the stability of polymeric micellar formulations of hydrophobic drugs such as cyclosporine A (CyA) in blood, and predict the in vivo performance of the examined delivery system. Poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) copolymers were assembled to polymeric nano-containers for the physical encapsulation of CyA by a co-solvent evaporation method using different loading conditions. CyA-loaded micelles were prepared and compared to commercially available intravenous formulation of CyA (Sandimmune) for in vitro release, protein binding, and pharmacokinetic parameters in Sprague-Dawley rats. The unbound fraction (fu) of CyA was determined using an erythrocyte vs. plasma and buffer partitioning technique. Different polymeric micellar formulations of CyA did not show any significant difference in CyA release when dialyzed against bovine serum albumin. The fu experiments, however, revealed a significant decrease in the fu of the loaded drug with an increase in the drug/polymer loading ratio, while the fu of all micellar formulations were significantly lower than Sandimmune. The pharmacokinetic study showed that fu of CyA in each formulation correlated with its in vivo performance determined by pharmacokinetic parameters: the lower fu of the formulation, translated to a higher area under the concentration versus time curve (AUC), and a lower clearance (CL) and volume of distribution (Vd). In conclusion, determination of the unbound fraction of encapsulated drug can be used to predict the in vivo stability of polymeric micellar nano-containers. PEO-b-PCL micelles containing higher CyA-loaded levels are shown to be more stable changing the pharmacokinetics of the encapsulated CyA to a higher extent.

Silicone-based polymers with reduced protein adsorption were successfully prepared by incorporating mono- or bifunctional poly(ethylene oxide) (PEO) derivatives, respectively, into PDMS during rubber formation using classic room temperature vulcanization chemistry. Characterization of the films by water contact-angle measurements and XPS showed that the PEO was present on the film surface, with greater amounts of PEO at the interface modified with monofunctional PEO. Scanning electron microscopy showed the PEO domains segregated into regular zigzag patterns on the PEO-modified surfaces. Significant reductions in the adsorption of fibrinogen, albumin and lysozyme were observed on both PEO-modified surfaces, although the monofunctional PEO surfaces performed much better in this regard. The reductions in protein adsorption were comparable for all three proteins on both surfaces, suggesting that molecular mass of the protein is not a significant factor in determining the magnitude of protein deposition. Western blot studies showed that the adsorption of proteins from plasma to the monofunctional PEO-modified surfaces was also significantly reduced and surprisingly selective, with very few bands noted relative to the control surfaces and those modified with bifunctional PEO.

Amphiphilic <em>PEO</em>-silanes (a-c) having siloxane tethers of varying lengths with the general formula alpha-(EtO)3Si-(CH2)2-oligodimethylsiloxane(n)-block-poly(ethylene oxide)8-OCH3 [n=0 (a), n=4 (b), and n=13 (c)] were grafted onto silicon wafers and resistance to adsorption of plasma proteins was measured. Distancing the <em>PEO</em> segment from the hydrolyzable triethoxysilane [(EtO)3Si] grafting group by a oligodimethylsiloxane tether represents a new method of grafting <em>PEO</em> chains to surfaces. Properties of surfaces grafted with a-c were compared to surfaces grafted with a traditional <em>PEO</em>-silane containing a propyl spacer [(EtO)3Si-(CH2)3-poly(ethylene oxide)8-OCH3, <em>PEO</em> control]. As the siloxane tether length increased, chain density of <em>PEO</em>-silanes grafted onto oxidized silicon wafers decreased and hydrophobicity of the <em>PEO</em>-silane increased which led to a decrease in surface hydrophilicity. Despite decreased surface hydrophilicity, resistance to the adsorption of bovine serum albumin (BSA) increased in the order: <em>PEO</em> control<a<b approximately c and to human fibrinogen (HF) increased in the order: <em>PEO</em> control<a<b<c.

Sulfhydryl selective reactions were explored to conjugate oligomers of a peptidomimetic integrin alphavbeta3 antagonist, 4-[2-(3,4,5,6-tetrahydropyrimidine-2-ylamino)ethyloxy]benzoyl-2-(S)-aminoethylsulfonylamino-beta-alanine (IA) to monoclonal antibody (MoAb) to increase integrin alphavbeta3 receptor-binding avidity. To generate sulfhydryl groups, N-succinimidyl-S-acetylthioacetate (SATA) was conjugated to both MoAb and IA. Sulfhydryl groups were then generated upon the deacetylation of the protecting acetyl group from the S-acetylthioacetato (ATA) moiety of MoAb-(ATA)n or IA-ATA with 0.02 M hydroxylamine in the presence of 1 mM EDTA at pH 7.2. The major focus was on optimizing the reaction concentrations, molar ratios, and reaction pH to conjugate high levels of IA-(A-SH) to MoAb-(A-SH)n without causing the inter- and intramolecular cross-linking of MoAb. Stepwise reactions of MoAb-(A-SH)n (15 microM MoAb) with a homobifunctional cross-linker, 1,8-bis(maleimido)diethylene glycol (BM[PEO]2) at a >50x molar excess to the -SH, followed by the reaction of the purified product MoAb-(A-S-succinimidomaleimido-[PEO]2)n with IA-(A-SH) at pH 7.2 afforded monomeric MoAb-(A-S-succinimido-[PEO]2-succinimido-S-A-IA)n with <10% high molecular weight oligomeric MoAb. Monomeric MoAb-(A-S-S-[PEO]2-S-S-A-IA)10 (MoAb-IA10) radiolabeled with 111In using 2-(p-isothiocyanatobenzyl)cyclohexyl-DTPA and with 125I using the Iodogen method showed >70% bindability to 0.4 microM alphavbeta3. When injected iv to nude mice with the receptor-positive M21 tumor, MoAb-IA10 radiolabeled with both 111In and 125I accumulated rapidly and was retained in the tumor for a 44 h period while the radioactivity cleared rapidly from the blood, thereby resulting in increasing tumor-to-blood ratios over time. The tumor uptake was similar between the 125I label and the 111In label for a 44 h period. In contrast, the blood radioactivity was lower, but liver and other organ uptakes were much higher for the 111In label than for the 125I. The 111In label produced higher tumor-to-blood ratios but much lower tumor-to-organ ratios than the 125I. The rapid blood clearance, a short peak tumor uptake time, and a low peak tumor uptake value with prolonged tumor retention of this macromolecule appear to support a hypothesis that MoAb-IA10 primarily binds to alphavbeta3 receptors on angiogenic vessels, but not on the tumor. This hypothesis was substantiated by the fluorescence microscopic analysis of FITC-MoAb-IA10, which showed that FITC-MoAb-IA10 outlined neovasculatures but not tumor cells at 4 and 21 h ex vivo. Additional proof was observed when blood vessels outlined with rhodamine-lectin, which specifically binds to blood vessels, were superimposable on neovasculatures outlined with FITC-MoAb-IA10.

OBJECTIVE

To map the gene responsible for autosomal dominant progressive external opthalmoplegia.

BACKGROUND

The pathogenesis of progressive external ophthalmoplegia (PEO) can be associated with multiple deletions of mitochondrial DNA (mtDNA). PEO may show autosomal dominant (adPEO) or autosomal recessive (arPEO) patterns of inheritance, indicating that the genetic defect has a Mendelian basis and most likely involves a nuclear gene encoding a protein that interacts with the mitochondrial genome. adPEO is heterogeneous genetically, and thus far disease loci have been identified on chromosomes 3 and 10. The locus on chromosome 10q23-q25 was assigned by linkage analysis in a single Finnish family.

METHODS

Samples from a large Pakistani family with adPEO, in which clinical symptoms are bilateral ptosis, limitations of eye movements, and varying degrees of proximal muscle weakness, were collected. Muscle biopsy and mtDNA rearrangement analysis was used to confirm the diagnosis. Genomewide linkage analysis was set up using a set of 391 microsatellite markers.

RESULTS

The muscle biopsy from an affected member showed ragged red fibers, increased succinic dehydrogenase staining, lack of cytochrome oxidase activity, and multiple deletions of mtDNA. The disease locus was mapped to 10q23.31-q25.1 by linkage analysis, and a maximum lod score of 5.72 was obtained with D10S1267.

CONCLUSIONS

By analysis of meiotic recombinations in affected individuals, the critical region was restricted to the 7-cM interval between D10S198 and D10S1795.

We examined changes in a poly(ethylene oxide) (PEO) coating by continuously monitoring the electroosmotic flow (EOF) in a fused-silica capillary during electrophoresis. An imaging CCD camera was used to follow the motion of a fluorescent neutral marker zone along the length of the capillary. The PEO coating was shown to reduce the velocity of EOF by more than 1 order of magnitude compared to a bare capillary at pH 7.0. However, it did not reduce EOF efficiently at pH 8.2. The coating protocol was important, especially at an intermediate pH of 7.7. Capillary reconditioning with an acidified solution of PEO was necessary in order to create a stable and efficient coating. In all cases we observed a gradual increase of EOF during extended runs, suggesting that the coating is slowly being degraded. The increase of pH in the cathodic (detection-end) buffer reservoir beyond pH ∼8.0, e.g., as a result of electrolysis, had a large impact on the stability of the coating. This phenomenon may be used for the efficient and fast regeneration of the column surface and provides a simpler and more reliable alternative to pressure flushing of the capillary.

In situ cross-linkable hybrid hydrogels composed of gelatin and 4-arm-polypropylene oxide-polyethylene oxide (Tetronic) was developed as an injectable scaffold for tissue regeneration. The gelatin was modified by hydroxyphenyl propionic acid (HPA) and the Tetronic was conjugated with tyramines (Tet-TA). The hydrogels were rapidly formed by mixing the polymer solutions containing horseradish peroxidase (HRP) and hydrogen peroxide (H(2)O(2)). The gelation time and mechanical properties of the hydrogels could be controlled by varying the HRP and H(2)O(2) concentrations. In vitro degradation study of the hybrid hydrogels was carried out using collagenase and the prolonged proteolytic degradation was obtained due to the presence of the Tetronic. Human dermal fibroblast (hDFB) was cultured in the hydrogel matrices to evaluate the cyto-compatibility. The encapsulated cells were shown to be highly viable and spread over the gel matrices, suggesting that the hybrid hydrogels have an excellent cyto-compatibility. The hydrogels were also subcutaneously injected in the back of mice and the results demonstrated that the hydrogels were rapidly formed at the injected site. From these results, we demonstrate that the in situ cross-linkable hydrogels formed by hybridization of gelatin and Tetronic via enzyme-mediated reactions hold great promise for use as injectable matrices for tissue regenerative medicine due to their tunable physico-chemical properties and excellent bioactivity.

Autosomal dominant PEO is associated with mutations in a number of nuclear genes affecting the intergenomic communication with mitochondrial DNA. We report a Spanish family showing a mild phenotype characterized by autosomal dominant ocular myopathy and morphological signs of mitochondrial dysfunction, that harboured a novel c.1071G>C (p.R357P) mutation in the hot-spot linker region of the twinkle protein.

OBJECTIVE

Amphiphilic biocompatible polyoxyethylene (PEO)-based polymers form particles (micelles) that are 10-50 nm in diameter. In the current research, we successfully incorporated amphiphilic indium-111 (111In) and gadolinium chelates into these particles and used them as particulate contrast media in percutaneous lymphography.

METHODS

Micelles of amphiphilic PEO-lipid conjugates were loaded with 111In and gadolinium diethylenetriamine pentaacetic acid-phosphatidylethanolamine (Gd-DTPA-PE) and were injected subcutaneously into the rabbit's paw. Corresponding images of local lymphatics were acquired using a gamma camera and a magnetic resonance (MR) imager.

RESULTS

The entire lymphatic chain from the paw to the thoracic duct could be visualized using 111In micelles after injection site massage. T1-weighted MR images of the primary lymph node and collecting vessels were obtained within 4 min after administration of gadolinium micelles and massage.

CONCLUSIONS

Polymeric PEO-containing micelles can be loaded with diagnostic metals and, on subcutaneous injection, can visualize elements of lymphatic system. The major fraction of injected micelles stays within the lymph fluid, thus serving as lymphangiographic agents for indirect MR or gamma lymphography.

Controlled delivery of multiple therapeutic agents can be considered as an effective approach in skin tissue engineering. In this study, recombinant human epidermal growth factor (rhEGF) and recombinant human basic fibroblast growth factor (rhbFGF) encapsulated in PLGA microspheres were loaded in hybrid scaffolds of PLGA and PEO. The scaffolds with various formulations were fabricated through electrospinning in order to maintain dual, individual or different release rate of rhEGF and rhbFGF. Morphological, physical and mechanical properties of the scaffold were investigated. The scaffold possessed uniform morphology with an average diameter of 280 nm for PLGA and 760 nm for PEO nanofibers. Furthermore, the mechanical properties of the scaffolds were shown to be akin to those of human skin. Bioactivity of the scaffolds for human skin fibroblasts was evaluated. The HSF acquired significant proliferation and well-spread morphology on the scaffolds particularly in the case of different release rate of rhEGF and rhbFGF which implies the synergistic effect of the growth factors. Additionally, collagen and elastin gene expression was significantly up-regulated in the HSF seeded on the scaffolds in the case of individual delivery of rhEGF and dual delivery of rhEGF and rhbFGF. In conclusion, the prepared scaffolds as a suitable supportive substrate and multiple growth factor delivery system can find extensive utilization in skin tissue engineering.

Fibrous scaffolds are finding wide use in the field of tissue engineering, as they can be designed to mimic many native tissue properties and structures (e.g., cardiac tissue, meniscus). The influence of fiber alignment and scaffold architecture on cellular interactions and matrix organization was the focus of this study. Three scaffolds were fabricated from the photocrosslinkable elastomer poly(glycerol sebacate) (PGS), with changes in fiber alignment (non-aligned (NA) versus aligned (AL)) and the introduction of a PEO sacrificial polymer population to the AL scaffold (composite (CO)). PEO removal led to an increase in scaffold porosity and maintenance of scaffold anisotropy, as evident through visualization, mechanical testing, and mass loss studies. Hydrated scaffolds possessed moduli that ranged between ∼3-240 kPa, failing within the range of properties (<300 kPa) appropriate for soft tissue engineering. CO scaffolds were completely degraded as early as 16 days, whereas NA and AL scaffolds had ∼90% mass loss after 21 days when monitored in vitro. Neonatal cardiomyocytes, used as a representative cell type, that were seeded onto the scaffolds maintained their viability and aligned along the surface of the AL and CO fibers. When implanted subcutaneously in rats, a model that is commonly used to investigate in vivo tissue responses to biomaterials, CO scaffolds were completely integrated at 2 weeks, whereas ∼13% and ∼16% of the NA and AL scaffolds, respectively remained acellular. However, all scaffolds were completely populated with cells at 4 weeks post-implantation. Polarized light microscopy was used to evaluate the collagen elaboration and orientation within the scaffold. An increase in the amount of collagen was observed for CO scaffolds and enhanced alignment of the nascent collagen was observed for AL and CO scaffolds compared to NA scaffolds. Thus, these results indicate that the scaffold architecture and porosity are important considerations in controlling tissue formation.

The reactive thermal-sensitive hydrogels, which combined the reversible thermosensitive and mild reactive property, were designed based on thiol-ene reaction in physiological conditions between thiol and acrylate capped thermosensitive Poloxamer 188. The modified P188A, P188SH, and their reactivity were characterized by (1)H NMR, FT-IR, GPC, DSC, Ellman method, and Rheometer. It was found that the thiol-ene reaction was pH and thermal-sensitive. There was 77.7% SH involved into the reaction at 37.0 degrees C and pH 7.4 within the first 30 min. The most of molecules reacted as CC/SH mol ratio was 1.5. The exothermic thiol-ene reaction was mild, with about DeltaH = -91.18 J/g changes. The multiblocks or network structure limited the dissolution of hydrogel, correspondingly the gel's duration and the release time of methylene blue were prolonged to 124 h. The experimental results indicated the reactive thermal-sensitive hydrogel's potential applications in drug delivery, tissue engineering, and cell encapsulation.

Polydopamine (PDA) nanoparticles can be used as an adsorbent with excellent adsorption capacity. However, nanosized adsorbents are prone to aggregation and thus are severely limited in the field of adsorption. In order to solve this problem, we utilized polydopamine in-situ oxidation self-polymerization on the surface of polycaprolactone (PCL)/polyethylene oxide (PEO) electrospun fiber after solvent vapor annealing (SVA) treatment, and successfully designed and prepared a PCL/PEO@PDA composite membrane. The SVA treatment regulated the microscopic morphology of smooth PCL/PEO electrospun fibers that exhibited a pleated microstructure, increasing the specific surface area, and providing abundant active sites for the anchoring of PDA nanoparticles. The PCL/PEO@PDA composite obtained by chemical modification of PDA demonstrated numerous active sites for the adsorption of methylene (MB) and methyl orange (MO). In addition, the PCL/PEO@PDA composites were reusable several times with good reutilization as adsorbents. Therefore, we have developed a highly efficient and non-agglomerated dye adsorbent that exhibits potential large-scale application in dye removal and wastewater purification.

The end-product of the electrospinning process is typically a randomly aligned fiber mesh or membrane. This is a result of the electric field generated between the drop of polymer solution at the needle and the collector. The developed electric field causes the stretching of the fibers and their random deposition. By judicious selection of the collector architecture, it is thus possible to develop other morphologies on the nanofiber meshes. The aim of this work is to prepare fiber meshes using various patterned collectors with specific dimensions and designs and to evaluate how those patterns can affect the properties of the meshes relevant to biomedical applications. This study aims at verifying whether it is possible to control the architecture of the fiber meshes by tailoring the geometry of the collector. Three different metallic collector topographies are used to test this hypothesis. Electrospun nonwoven patterned meshes of polyethylene oxide (PEO) and poly( -caprolactone) (PCL) were successfully prepared. Those fiber meshes were analyzed by scanning electron microscopy (SEM). Both mechanical properties of the meshes and cell contacting experiments were performed to test the effect of the produced patterns over the properties of the meshes relevant for biomedical applications. The present study will evaluate cell adhesion sensitivity to the patterns generated and the effect of those patterns on the tensile properties of the fiber meshes.

The ternary phase diagram of the amphiphilic triblock copolymer PEO-PPO-PEO ((EO)(20)(PO)(70)(EO)(20) commercialized under the generic name P123), water, and ethanol has been investigated at constant temperature (T = 23 degrees C) by small-angle X-ray scattering (SAXS). The microstructure resulting from the self-assembly of the PEO-PPO-PEO block copolymer varies from micelles in solution to various types of liquid crystalline phases such as cubic, 3D hexagonal close packed spheres (HCPS), 2D hexagonal, and lamellar when the concentration of the polymer is increased. In the isotropic liquid phase, the micellar structural parameters are obtained as a function of the water-ethanol ratio and block copolymer concentration by fitting the scattering data to a model involving core-shell form factor and a hard sphere structure factor of interaction. The micellar core, the aggregation number, and the hard sphere interaction radius decrease when increasing the ethanol/water ratio in the mixed solvent. We show that the fraction of ethanol present in the core is responsible for the swelling of the PPO blocks. In the different liquid crystalline phases, structural parameters such as lattice spacing, interfacial area of PEO block, and aggregation number are also evaluated. In addition to classical phases such as lamellar, 2D hexagonal, and liquid isotropic phases, we have observed a two-phase region in which cubic Fm3m and P6(3)mmc (hexagonally close packing of spheres (HCPS)) phases coexist. This appears at 30% (w/w) of P123 in pure water and with 5% (w/w) of ethanol. At 10% (w/w) ethanol, only the HCPS phase remains present.

The electrical conductivity of D2O-in-n-heptane microemulsions stabilized by cationic/nonionic surfactant mixtures was studied as a function of D2O content, surfactant concentration, and surfactant mixture composition. The surfactants employed were cationic di-n-didodecyldimethylammonium bromide, DDAB, nonionic poly(oxyethylene) monododecyl ethers, C12EJ, with J=3-8 and 23, nonionic polymeric surfactants of the type PEO-PPO-PEO (Pluronic), and the reverse structure analogues (Pluronic R). Qualitative structural information was drawn from a comparison between the measured conductivity and that predicted by the charge fluctuation model for spherical droplets. The conductivity versus water content curves were found to be typical for water-in-oil systems composed of spherical droplets. From the effect of blending nonionic surfactant with DDAB on the measured conductivities, it was concluded that microemulsion conductivity is independent of the concentration of cationic surfactant (DDAB). This finding agrees well with theoretical microemulsion conductivity models.

The purpose of the research was to investigate the changes in physicochemical properties and their influence on nasal formulation performance using 5-factor, 3-level Box-Behnken experimental design on the combined responses of viscosity, droplet size distribution (DSD), and drug release. Gel formulations of hydroxyurea (HU) with surface-active polymers (hydroxyethylcellulose [HEC] and polyethylene-oxide [PEO]) and ionic excipients (sodium chloride and calcium chloride) were prepared using Box-Behnken experimental design. The rheology and dynamic surface tension (DST) of the test formulations was investigated using LV-DV-III Brookfield rheometer and T60 SITA tensiometer, respectively. Droplet size analysis of nasal aerosols was determined by laser diffraction using the Malvern Spraytec with the InnovaSystems actuator. In vitro drug release studies were conducted on Franz diffusion cells. With PEO gel, calcium chloride increased the viscosity and DSD and retarded drug release, while sodium chloride decreased the viscosity, DST, and DSD and accelerated the release of HU. With HEC gel, the addition of the above salts resulted in less significant changes in viscosity, DSD, and DST, but both salts significantly increased the release of HU. Droplet size data obtained from a high viscosity nasal pump was dependent on type of polymer, polymer-excipient interactions, and solvent properties. The applications of Box-Behnken experimental design facilitated the prediction and identified major excipient influences on viscosity, DSD, and in vitro drug release.

Low protein adsorbing polymer films have been prepared with which to fabricate intravenous containers, designed for compatibility with low concentrations of protein drugs. The material is economically manufactured utilizing physical melt blending of water-soluble surface-modifying polymers (PEO, PEOX, PVA, and PNVP) with a base polymer (EVA, PP, PETG, PMMA, SB, and nylon). Permanency of the hydrophilic surfaces so generated was confirmed by surface contact angle experiments and total organic carbon leachables analysis of the aqueous contacting solutions. Binding of IgG, albumin and insulin was studied. A sixfold reduction of protein adsorption was obtained by adding 5% PVA13K to EVA, for IgG at a bulk concentration of 2.5 ppm. Surface bound protein measured by micro-BCA colorimetry, agreed with the solution protein lost, as determined by the Fluoraldehyde procedure. Imaging of the protein exposed plastic surfaces by silver enhanced protein conjugated gold staining agreed with the quantitative assay determinations.

Pluronic surfactants, PEO-PPO-PEO triblock copolymers, have been investigated widely due to their protein-resistant properties in applications as coatings for implants and in controlled drug release systems. We have studied a wide range of these copolymers, varying in both PEO and PPO block size, by adsorbing them to a polystyrene surface and investigating their subsequent resistance to human serum albumin adsorption. This investigation has been carried out in real time, using surface plasmon resonance, with the surfaces subsequently visualized by atomic force microscopy. This approach has allowed determination of the effect of the lengths of the PEO and PPO polymer chains on protein resistivity. For low-molecular-weight Pluronics a significant, yet not complete, reduction in albumin adsorption has been observed whereas higher molecular weight Pluronics appear to completely inhibit adsorption within the time frame of this experiment. An increase in the PPO block size of the copolymer also appears to increase its protein resistance. This work further confirms that the binding strength of the anchoring block to the hydrophobic surface, rather than the length of the protruding hydrophilic PEO chains, determines a copolymer's protein resistance capability.

The gas sensors based on polymer-coated resonant microcantilevers for volatile organic compounds (VOCs) detection are investigated. A method to characterize the gas sensors through sensor calibration is proposed. The expressions for the estimation of the characteristic parameters are derived. The effect of the polymer coating location on the sensor's sensitivity is investigated and the formula to calculate the polymer-analyte partition coefficient without knowing the polymer coating features is presented for the first time. Three polymers: polyethyleneoxide (PEO), polyethylenevinylacetate (PEVA) and polyvinylalcohol (PVA) are used to perform the experiments. Six organic solvents: toluene, benzene, ethanol, acetone, hexane and octane are used as analytes. The response time, reversibility, hydrophilicity, sensitivity and selectivity of the polymer layers are discussed. According to the results, highly sensitive sensors for each of the analytes are proposed. Based on the characterization method, a convenient and flexible way to the construction of electric nose system by the polymer-coated resonant microcantilevers can be achieved.