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Nanoscale zerovalent iron (Fe0) on carbon materials was successfully synthesized via a simple one-step pyrolysis of coir pith with iron precursor. The Fe0 dispersion over activated carbon (AC) and stability was amended by adding polyethylene glycol (PEG)/carboxymethyl cellulose (CMC). The transmission electron microscopy results reveal the homogeneous distribution of Fe0 (~20 nm) on the surface of AC. In addition, the crystal patterns and valence states of Fe0 nanoparticles were evaluated by X-ray diffraction, and X-ray photoelectron spectroscopy, respectively. Trichloroethylene (TCE), one common pollutant in the groundwater, was used to understand the catalytic ability of Fe/AC. The pseudo-first-order kinetic model was applied for TCE removal rate. Fe/AC shows 80% TCE removal in 24 h reaction time, due to its porous structure and large surface area. PEG-Fe/AC composite demonstrated 90.4% TCE dechlorination efficiency in 45 min (kobs 0.29 min−1). The enhanced dechlorination was recorded due to perfect PEG and Fe0 ratio, in which PEG restricted the arial oxidation of Fe0. The as-synthesized nanocomposite was further evaluated for its high stability and efficacy by consecutive eight successive TCE removal cycles. This study demonstrates that one-pot synthesized PEG-Fe/AC composite can effectively remove chlorinated compounds in water, which can be beneficial to the future research applications.

Moringa oleifera (Lam.) is a nutritious plant species that has the potential to alleviate food insecurity in low- and middle-income regions. However, the bitter taste associated with M. oleifera leaves is a key barrier to its acceptance as food. It was hypothesized that reducing the bitterness in M. oleifera-fortified instant soups would increase their acceptance. Acid soaking and the addition of a sweetener (aspartame) were examined for their effectiveness in the removal of bitter taste in M. oleifera leaves. Fifty assessors rated the acceptance and perceived bitterness in a randomized complete block sensory evaluation. South Indian instant soup samples with 0%, 50% and 100% replacement of vegetable powder with M. oleifera leaf powder were evaluated. Acceptance for M. oleifera-fortified instant soups was higher for samples with lower perceived bitterness. Addition of sweetener was found to be effective in increasing the acceptability and reducing the perceived bitterness at the 50% replacement level, but not at the 100% replacement level. Perceived bitterness did not decrease in formulations with acid-soaked M. oleifera leaves. Undesirable organoleptic properties need to be masked or removed for the acceptance of M. oleifera leaves as a regular food. We recommend that foods fortified with M. oleifera to include a sweet excipient to reduce the bitter tastes. Fortified instant soup samples with reduced perceived bitterness had increased acceptability. Debittered M. oleifera-fortified foods would appeal to consumers, which would increase their consumption and could lead to reduced prevalence of micronutrient deficiencies.

OBJECTIVES: Moringa oleifera is an edible tropical plant with the potential to alleviate micronutrient deficiencies in low and middle income nations. This study addresses two barriers for the consumption of M. oleifera leaves: (1) inconsistencies between the actual nutritional value and common nutritional claims and (2) its bitterness. It was hypothesized that the reduction of bitterness in M. oleifera-fortified foods would increase their acceptability. METHODS: The micronutrient content of M. oleifera leaves from India and Nigeria was determined in this study and compiled along with literature values. Data on M. oleifera were compared against spinach and carrot for minerals and carotenoids respectively. The effectiveness of acid soaking and addition of sweetness (aspartame) as debittering treatments was examined using a full factorial design. A sensory evaluation (randomized complete block, 9-point hedonic scale) with 50 assessors examined the preference and bitterness in 7 fortified instant soup mix formulations with varying levels of debittered M. oleifera leaf powder. RESULTS: Results of this study do not support nutritional claims asserting that M. oleifera contains 25 times more iron than spinach and 10 times more vitamin A than carrots. M. oleifera contains, at most, 3.4 times more iron than dried spinach. The equivalent vitamin A content in M. oleifera was found to be 55% lower than that in dried carrots. These inconsistencies may be a result of nutritional comparisons made between inequivalent moisture contents, as dried M. oleifera leaves have 18 times more iron than fresh spinach by weight. The control (no fortification) formulation was most preferred, followed by formulations with 50% replacement by M. oleifera. The addition of sweetness significantly reduced bitterness and increased acceptance of fortified soup mix formulations. CONCLUSIONS: M. oleifera's nutritional content is lower than that asserted by common nutritional claims, but its abundance in food insecure regions and wide range of nutrients maintain its potential as a nutritious food source for populations low and middle income nations. It is recommended that M. oleifera-fortified food products include a sweet excipient to reduce bitterness to increase acceptability. FUNDING SOURCES: This research was funded by the Centre for Global Engineering (University of Toronto) and Mitacs Canada. SUPPORTING TABLES, IMAGES AND/OR GRAPHS

To determine the outward permeability of retina-choroid-sclera (RCS) layer for different ophthalmic drugs and to develop correlations between drug physicochemical properties and RCS permeability. A finite volume model was developed to simulate pharmacokinetics in the eye following drug administration by intravitreal injection. The RCS permeability was determined for 32 compounds by best fitting the drug concentration-time profile obtained by simulation with previously reported experimental data. Multiple linear regression was then used to develop correlations between best fit RCS permeability and drugs physicochemical properties. The RCS drug permeabilities had values that ranged over 3 × 10−6 m/s. Regression analysis for hydrophilic compounds showed that more than 92% of the variation in permeability values can be explained by correlative models of drug properties that include logarithm of the octanol-water partition coefficient (LogP), protein binding (PB), number of hydrogen bond acceptors (HBA), hydrogen bond donors (HBD), polar surface area (PSA) and dissociation constant (pKa) as independent variables. Regression analysis for lipophilic compounds showed that no significant correlation can be found between just physicochemical properties and RCS permeability. Using the RCS permeability obtained from this study for different drugs, one can predict pharmacokinetics of intravitreal drug delivery systems such as solid implants or colloidal systems. Furthermore, the developed correlations between RCS permeability and physicochemical properties of drugs are useful in early drug development by predicting RCS permeability and drug concentration in the vitreous without experimental data.

Polydimethylsiloxane-poly(methacrylic acid—hydroxyethyl methacrylate) interpenetrating polymer networks (PDMS-P(MAA–HEMA) IPN) were formulated and polymerized simultaneously from bicontinuous microemulsion templates. Microemulsions containing reactive silicone oils and MAA/HEMA in aqueous solution were stabilized with silicone surfactants, and were then reacted at 50 °C for 3 h under an N2 atmosphere. The formation of bicontinuous morphology was confirmed by laser scanning confocal microscopy, reversible swelling behavior, differential scanning calorimetry, texture analysis, and permeability to vitamin B12 in aqueous solution. Incorporating polymerizable surfactants into the microemulsion aided in stabilizing the initial microemulsion structure during polymerization, yielding a more uniform IPN morphology with domain sizes of

This article introduces the formulation of alcohol-free, lecithin microemulsion-based gels (MBGs) prepared with gelatin as gelling agent. The influence of oil, water, lecithin and hydrophilic and lipophilic additives (linkers) on the rheological properties and appearance of these gels was systematically explored using ternary phase diagrams. Clear MBGs were obtained in regions of single phase microemulsions (μEs) at room temperature. Increasing the water content in the formulation increased the elastic modulus of the gels, while increasing the oil content had the opposite effect. The hydrophilic additive (PEG-6-caprylic/capric glycerides) was shown to reduce the elastic modulus of gelatin gels, particularly at high temperatures. In contrast to anionic (AOT) μEs, the results suggest that in lecithin (nonionic) μEs, the introduction of gelatin “dehydrates” the μE. Finally, when the transdermal transport of lidocaine formulated in the parent μE and the resulting MBG were compared, only a minor retardation in the loading and release of lidocaine was observed.

In this work, for the first time, the Hydrophilic-Lipophilic Difference (HLD) framework for microemulsion formulation has been applied to silicone oils and silicone alkyl polyether surfactants. Based on the HLD equations and recently introduced mixing rules, we have quantified the hydrophobicity of the oils according to the equivalent alkane carbon number (EACN). We have found that, in a reference system containing sodium dihexyl sulfosuccinate (SDHS) as the surfactant, 0.65 centistoke (cSt) and 3.0 cSt silicone oils behave like n-dodecane and n-pentadecane, respectively. Silicone alkyl polyether surfactants were found to have characteristic curvatures ranging 3.4-18.9, exceeding that of most non-ionic surfactants. The introduction of methacrylic acid (MAA) and hydroxyethyl methacrylate (HEMA) to the aqueous phase caused a significant negative shift in HLD, indicative of an aqueous phase that is less hydrophilic than pure water. The more hydrophobic surfactants (largest positive curvatures) were used in order to compensate for this effect. These findings have led to the formulation of bicontinuous microemulsions (μEs) containing silicone oil, silicone alkyl polyether and reactive monomers in aqueous solution. Ternary phase diagrams of these systems revealed the potential for silicone-containing polymer composites with bicontinuous morphologies. These findings have also helped to explain the phase behavior of formulations previously reported in literature, and could help in providing a systematic, consistent approach to future silicone oil based microemulsion formulation.

Quartz crystal microbalance (QCM) was used to study the self-assembly of per-6-thio-β-cyclodextrin (t7-βCD) on gold surfaces, and the subsequent inclusion interactions of immobilized βCD with adamantane-poly(ethylene glycol) (5,000 MW, AD-PEG), 1-adamantanecarboxylic acid (AD-C) and 1-adamantylamine (AD-A). From a 50 μM solution of t7-βCD in 60:40 DMSO:H2O, a t7-βCD layer was formed on gold with surface density of 71.7 ± 2.7 pmol/cm2, corresponding to 80 ± 3% of close-packed monolayer coverage. Gold sensors with immobilized t7-βCD were then exposed alternately to six different concentrations of AD-PEG, 500 μM AD-C or 500 μM AD-A aqueous solutions for association, and water for dissociation. Association of AD-PEG conformed to a Langmuir isotherm, with a best fit equilibrium constant K = 125,000 ± 18,000 M−1. For AD-C and AD-A, association (k a ) and dissociation (k d ) rate constants were extracted from kinetic profiles by fitting to the Langmuir model, and equilibrium constants were calculated. The parameters for AD-C were found to be: k a = 100 ± 5 M−1 s−1, k d = 110 (±18) × 10−4 s−1, and K = 9,400 ± 1,700 M−1. For AD-A, k a = 58 ± 6 M−1 s−1, k d = 154 (±7) × 10−4 s−1, and K = 3,800 ± 400 M−1. The results demonstrate the utility of QCM as a tool for studying small molecule surface adsorption and guest–host interactions on surfaces. More specifically, the kinetic and thermodynamic data of AD-C, AD-A, and AD-PEG inclusion with immobilized t7-βCD form a basis for further surface association studies of AD-X conjugates to advance surface sensory and coupling applications.

In this study, the silica-based organic-inorganic hybrid nanocomposites have been developed for applications as the hard coating on the PET substrate surface. The inorganic material was functional polysiloxane with polyheral oligomeric silsesquioxanes (POSS)-like nanostructures, prepared by sol-gel method using 3-(Methacryloyloxy)-propyltrimethoxysilane (MAPTMS) in the presence of an acidic catalyst. The polymer matrix used was the UV-curing polyurethane acrylate resin. The surface functional groups and the sizes of nanoparticles were controlled to ensure strong interaction between the nanoparticles and the polymer matrix, resulting in high transparency and abrasion-resistant nanocomposite coatings, as the organic-inorganic nanocomposite coatings exhibit great performance in hardness and visible light transmittance on the PET substrate. With good optical, mechanical and physical performance, the multifunctional transparent nanocomposite coatings are suitable for the applications in automotive, optoelectronics and electronics industries, etc.

We report the encapsulation of MIN6 cells, a pancreatic β-cell line, using thermally induced gelable materials. This strategy uses aqueous solvent and mild temperatures during encapsulation, thereby minimizing adverse effects on cell function and viability. Using a 2:1 mixture of PNIPAAm-PEG-PNIPAAm tri-block copolymer and PNIPAAm homopolymer that exhibit reversible sol-to-gel transition at ∼30°C, gels were formed that exhibit mechanical integrity, and are stable in H2O, PBS and complete DMEM with negligible mass loss at 37°C for 60 days. MTT assays showed undetectable cytotoxicity of the polymers towards MIN6 cells. A simple microencapsulation process was developed using vertical co-extrusion and a 37°C capsule collection bath containing a paraffin layer above DMEM. Spherical capsules with diameters ranging from 500 to 900 µm were formed. SEM images of freeze-dried capsules with PBS as the core solution showed homogenous gel capsule membranes. Confocal microscopy revealed that the encapsulated cells tended to form small aggregates over 5 days, and staining for live and dead cells showed high viability post-encapsulation. A static glucose challenge with day-5 cultured microencapsulated cells exhibited glucose-dependent insulin secretion comparable to controls of free MIN6 cells grown in monolayers. These results demonstrate the potential use of these thermo-responsive polymers as cell encapsulation membranes. Biotechnol. Bioeng. 2007;96: 146–155. © 2006 Wiley Periodicals, Inc.

Reversible addition-fragmentation chain transfer (RAFT) polymerization was used successfully to synthesize temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm), poly(methacrylic acid) (PMAA), and their temperature-responsive block copolymers. Detailed RAFT polymerization kinetics of the homopolymers was studied. PNIPAAm and PMAA homopolymerization showed living characteristics that include a linear relationship between Mn and conversion, controlled molecular weights, and relatively narrow molecular weight distribution (PDI < 1.3). Furthermore, the homopolymers can be reactivated to produce block copolymers. The RAFT agent, carboxymethyl dithiobenzoate (CMDB), proved to control molecular weight and PDI. As the RAFT agent concentration increases, molecular weight and PDI decreased. However, CMDB showed evidence of having a relatively low chain transfer constant as well as degradation during polymerization. Solution of the block copolymers in phosphate buffered saline displayed temperature reversible characteristics at a lower critical solution temperature (LCST) transition of 31°C. A 5 wt % solution of the block copolymers form thermoreversible gels by a self-assembly mechanism above the LCST. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 1191–1201, 2006

The objectives of this study are to probe the pH responsiveness of polydimethyl siloxane (PDMS)/polymethacrylic acid (PMAA) interpenetrating polymer networks (IPNs), and to relate pH-dependent changes in permeation to morphological changes. PDMS/PMAA IPNs of 70:30 mass ratio on a dry basis were prepared using a monomer immersion method [Macromolecules 33 (10) (2000) 3714]. IPNs made by this method have previously been shown to exhibit a bicontinuous morphology at pH 7 with PMAA structural features of 10–200 nm in dimension [Macromolecules 36 (6) (2003) 1962]. Equilibrium hydration, morphology and diffusion characteristics of the IPNs were investigated at different pH. Equilibrium hydration was gravimetrically determined to be in the range of 0.77–0.9 at pH 7 and 0.42–0.5 at pH 3, corresponding to average hydrations of 0.93 and 0.74 of the PMAA component, respectively. Morphology imaged using laser scanning confocal microscopy (LSCM) showed that the area fraction of fluorescein isothiocyanate labelled dextran (FITC-dextran) accessible regions decreased from pH 7 to 3, consistent with hydration data. Additionally at pH 3, the hydrogel domain appeared to be disconnected. Vitamin B12 (VB12) permeability through the IPN was found to be 1.7 × 10−7 cm2/s at pH 7, and below detection (

We previously reported on a novel system termed Lipobead that consists of hydrogel beads encased within an anchored lipid bilayer. The hydrogel particles are formed by inverse suspension polymerization of dimethylacrylamide with N,N'-ethylenebis(acrylamide). During the polymerization stage, the water in oil emulsion is interfacially stabilized by small molecule surfactants as well as a small percentage of lipid functionalized with a vinyl group. The functionalized lipid becomes tethered to the bead surface and promotes the assembly of a lipid bilayer on the surface of the hydrogel beads. The presence of the functionalized lipid during polymerization dramatically alters the yield, average size, and size distribution of beads produced. This paper examines the effect of various chemical and physical processing parameters on the average size and size distribution of beads produced when lipid is a component of the surfactant mixture. Relationships between the processing parameters, average bead size, and size distribution were established. Macroscopic properties of the lipid bilayers of Lipobeads were also evaluated including phase transition temperature as well as permeability to the small polar molecule, adenosine triphosphate. It was established that the presence of functionalized lipid improves the organization of the bilayer on the Lipobead surface.

The overall objective of our work was to make a hydrogel-supported phospholipid bilayer that models a cytoskeleton-supported cell membrane and provides a platform for studying membrane biology. Previously, we demonstrated that a pre-Lipobead, consisting of phospholipids covalently attached to the surface of a hydrogel, could give rise to a Lipobead when incubated with liposomes because the attached phospholipids promote self-assembly of a phospholipid membrane on the pre-Lipobead. We now report the properties of that Lipobead membrane. The lateral diffusion coefficient of fluorescently labeled phosphatidylcholine analogs in the membrane was measured by fluorescence recovery after photobleaching and was found to decrease as the surface anchor density and hydrogel crosslinking density increased. Results from the quenching of phosphatidylcholine analogs suggest that the phospholipid membrane of the Lipobead was composed mostly of a semipermeable lipid bilayer. However, the diffusional barrier properties of the Lipobead membrane were demonstrated by the entrapment of 1.5–3.0K dextran molecules in the hydrogel core after liposome fusion. This hydrogel-supported bilayer membrane preparation shows promise as a new platform for studying membrane biology and for high throughput drug screening.

Direct visualization of IPN morphology formed during polymerization-induced phase separation (PIPS) of PDMS−PMAA IPNs is reported. Laser scanning confocal microscopy (LSCM) and hydrophilic fluorescent probes of varying molecular weights were used to image hydrophilic domains in PDMS−PMAA IPNs. The images reveal complex, superimposed structures of hydrophilic domains of varying sizes and spatial distributions. This morphology is attributed to the phase-separated structures formed and partially arrested at continuously varying quench depths during the PIPS process. These observations contribute to the understanding of morphology development in IPNs.

We have synthesized a phospholipid−hydrogel conjugate that appears to drive the self-assembly of lipid membranes. A one-step radical polymerization synthesis of the conjugate was devised using lipi...

We report the development of a new gelation mechanism and a new family of polymers that self-assembles to form gels in a thermoreversible fashion. The polymers are block or star copolymers with a central hydrophilic poly(ethylene glycol) (PEG) segment (A) and temperature responsive poly(N-isopropylacrylamide) (PNIPAAm) terminal segments (B). Copolymers of various architectures, AB, A(B)2, A(B)4, and A(B)8, were synthesized to investigate the structures and properties relationship. At 5 °C, the viscosities of 20 wt % solutions were between 700 and 950 cP, and they could be easily injected through a 25 G needle. Upon warming to body temperature, A(B)2, A(B)4, and A(B)8 formed a strong associative network gel with aggregates of PNIPAAm segments acting as physical cross-links, whereas AB formed a weaker gel by micellar packing and entanglement. The values of elastic modulus, loss tangent, and yield strength were 1000−2500 Pa, 0.24−0.62, and 200−860 Pa, respectively. The gelation kinetic was fast; a typical ge...

Poly(methacrylic acid) (PMAA) grafted porous PE membranes (PE-g-PMAA) were studied. It was found that (1) a wide range of graft yields can be achieved by varying irradiation time (20–240 min) and monomer concentration (0.22M–0.66M), (2) the grafted membrane exhibits reversible permeability response, (3) the membrane shows a maximum permeability response at an intermediate permeant molecular weight due to size exclusion effect, and (4) depending on the graft yield, two types of permeability response can be obtained. These observations are consistent with our earlier study on poly(N-isopropylacrylamide) (PNIPAAm)–grafted porous polyethylene membranes. In addition, it was observed that the solvent used during grafting may influence the graft location—presumably due to variations in pore wetting. Specifically, compared to water solvent, methanol can increase grafting inside membrane pores, an observation inferred from membrane swelling, thickness measurement, and SEM characterization. Moreover, preferential grafting inside the membrane pores, as affected by increasing methanol content in the grafting solvent, results in lower membrane permeability and a greater pore graft-controlled type of permeability response. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 778–786, 2000

A monomer immersion sequential method for preparing PDMS−PMAA interpenetrating polymer networks (IPNs) was developed. Immersion of pre-IPN films in the guest monomer throughout synthesis ensured an even monomer concentration profile and produced a uniform bicontinuous morphology throughout the IPN indicative of phase separation by spinodal decomposition. Such IPNs were permeable to water-soluble compounds. Laser scanning confocal microscopy (LSCM) of the swollen IPNs allowed direct visualization of the morphology. PDMS−PMAA sequential IPNs synthesized while in contact with surfaces were also examined. Contact with glass or air during synthesis resulted in spatially varying morphology ranging from dispersed hydrogel domains near the surface to a bicontinuous morphology some distance below the surface. The morphology spectrum was attributed to a monomer concentration gradient created by monomer evaporation during handling of the pre-IPN film, as well as to substrate-dependent surface thermodynamic effects. ...

Grafting a temperature-responsive polymer, poly(N-isopropylacrylamide) (PNIPAAm), onto porous polyethylene (PE) membranes by UV irradiation was investigated. A wide range of graft yields (5–449%) was achieved by varying irradiation time (20–240 min) and monomer concentration (1.2–3.6 wt %). Characterization by XPS and SEM shows that the graft polymers are located both on the external surfaces as well as inside the pores of the membranes. Diffusional permeation experiments show that two distinct types of temperature responses were observed, depending on the graft yield; permeability increases with temperature in low graft yield membranes, while permeability decreases with temperature in high graft yield membranes. A mechanism explaining the dual valve functions of the graft membrane is proposed based on the location of the graft polymers on the membrane. It was also observed the permeability response exhibits a maximum with permeant molecular weight. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 70: 2133–2142, 1998

Stimuli-responsive membranes may act as “on–off switches” or “permeability valves”, producing patterns of pulsatile release, where the period and rate of mass transfer can be controlled by external or environmental triggers (e.g. pH, temperature, electric field). In this work, composite-heterogeneous polyelectrolyte gel (composite-HPG) membranes consisting of polymethacrylic acid (PMAA) gel particles dispersed within a polydimethylsiloxane (PDMS) network were developed and evaluated as pH-responsive membranes. The mechanism of permeability control for caffeine and vitamin B 12 through composite-HPG membranes was determined to be a synergistic function of membrane hydration and the percolating volume fraction of PMAA gel. Larger changes in permeation as a function of pH were achieved when both hydration and percolation effects occurred together than when either of these effects occurred on their own. Vitamin B 12 permeation was observed when the hydrated gel volume fraction was above approximately 0.38, but not below. Furthermore, the percolating fraction of composite-HPG membranes containing 28% (dry basis) PMAA gel particles was manipulated via pH to fall above (pH 7) or below (pH 3) this transition in permeability, resulting in membranes that delivered solutes of high molecular weight (vitamin B 12 ) with large on/off delivery ratios (160).

Effective diffusivity through heterogeneous media containing impermeable and geometrically anisotropic domains depends on the domain orientation relative to the diffusion direction. A particular class of heterogeneous membranes in which domain orientation can be controlled in situ, side-chain liquid-crystalline polymers (SCLCPs), are being investigated as responsive, or variable permeability membranes for use in a variety of applications including controlled release drug delivery. This paper describes a geometric model for predicting the effective diffusivity through this type of membranes as a function of domain orientation, volume fraction, and aspect ratio. Estimates of effective diffusivity were also generated using random walk simulations. Results from the two methods agree well with each other. Predicted effective diffusivities in systems with domains aligned either orthogonal or parallel to the diffusion direction are compared to results from available literature models. Model predictions are compared to experimentally obtained transport properties through SCLCPs in which liquid-crystalline domain orientation is modulated by externally applied electric field.

The majority of eyes that receive drug therapy exhibit some form of pathophysiological degradation. Two common pathophysiological states are retinal inflammation, which results in breakdown of the blood-retinal barrier, and aphakia. The purpose of this study was to examine the effects of aphakia and changes in retinal permeability and vitreous diffusivity on drug distribution in the vitreous humor of the human eye. The study was performed using a finite element model that accurately accounts for the vitreous geometry and boundary conditions. Intravitreal injection is the most common method for treating posterior segment disorders; therefore, this administration method was simulated using the models. Elimination from aphakic and phakic eyes was compared for four extreme injection locations and for two retinal permeabilities. When the retinal permeability was fixed at 5.0 x 10(-5) cm/s, increasing the drug diffusivity through the vitreous from 5.4 to 10(-7) to 2.4 x 10(-5) cm2/s decreased the half-life of drug from 64 hours to 2.7 hours. When the drug diffusivity was fixed at 5.6 x 10(-6) cm2/s, increasing the retinal permeability of the drug from 1.0 x 10(-7) to 1.0 x 10(-4) cm/s decreased the half-life of drug from 44 to 7 hours. Therefore, drug diffusivity and retinal permeability are key factors that influence elimination from the vitreous, and must be considered, particularly if the blood retinal barrier has been compromised. Faster drug elimination was observed in aphakic eyes than in phakic eyes, especially for drugs with a low retinal permeability and injected close to the lens capsule. Injection position is also important if the drug is injected in close proximity to a primary elimination barrier.

Direct intravitreal injection of drug is a common method for treating diseases of the retina or vitreous. The stagnant nature of the vitreous humor and surrounding tissue barriers creates concentration gradients within the vitreous that must be accounted for when developing drug therapy. The objective of this research was to study drug distribution in the vitreous humor of the rabbit eye after an intravitreal injection, using a finite element model. Fluorescein and fluorescein glucuronide were selected as model compounds due to available experimental data. All required model parameters were known except for the permeability of these compounds through the retina, which was determined by fitting model predictions to experimental data. The location of the intravitreal injection in the experimental studies was not precisely known; therefore, several injection locations were considered, and best-fit retinal permeability was determined for each case. Retinal permeability of fluorescein and fluorescein glucuronide estimated by the model ranged from 1.94 x 10(-5) to 3.5 x 10(-5) cm s(-1) and from 0 to 7.62 x 10(-7) cm s(-1), respectively, depending on the assumed site of the injection. These permeability values were compared with values previously calculated from other models, and the limitations of the models are discussed. Intravitreal injection position was found to be an important variable that must be controlled in both experimental and clinical settings.

Exact solutions have been obtained for the release kinetics of a solute from planar and spherical matrices into a finite external volume when the initial solute loading is greater than the solubility limit in the matrix. Moving boundary solutions are derived based on a combination of variable methods. The solutions make use of early time diffusion front positions obtained from previously available exact solutions for release from a planar matrix into an infinite sink. The results presented here indicate that as the external fluid volume increases, the fractional release at any time and the maximum fractional release increase. In addition, for a given external volume, as initial drug loading increases, the fractional release at any time decreases.

Lecithin-linker microemulsions are formulations produced with soybean lecithin in combination with a highly lipophilic (lipophilic linker) and highly hydrophilic (hydrophilic linkers) surfactant-like additives. In this work, lecithin-linker systems were formulated to produce self-emulsifying delivery systems for β-carotene and β-sitosterol. The concentration of the lipophilic linker, sorbitan monooleate, was adjusted to minimize the formation of liquid crystals. The concentration of hydrophilic linkers, decaglyceryl caprylate/caprate and PEG-6-caprylic/capric glycerides, was gradually increased (scanned) until single phase clear microemulsions were obtained. For these scans, the oil (ethyl caprate) to water ratio was set to 1. The single phase, clear microemulsions were diluted with fed-state simulated intestinal fluid (FeSSIF) and produced stable emulsions, with drop sizes close to 200 nm. Using pseudo-ternary phase diagrams to evaluate the process of dilution of microemulsion preconcentrates (mixtures of oil, lecithin and linkers with little or no water) with FeSSIF, it was determined that self-emulsifying systems are obtained when the early stages of the dilution produce single phase microemulsions. If liquid crystals or multiple phase systems are obtained during those early stages, then the emulsification yields unstable emulsions with large drop sizes. An in vitro permeability study conducted using a Flow-Thru Dialyzer revealed that stable emulsions with drop sizes of 150-300 nm produce large and irreversible permeation of β-carotene to sheep intestine. On the other hand, unstable emulsions produced without the linker combination separated in the dialyzer chamber.

The exact analytical solution and an approximate solution based on the variational formulation method have been obtained for the release kinetics of a solute from a spherical polymeric matrix in which the initial solute loading A is above the solubility limit Cs. Comparisons between these new solutions and previously reported approximate solutions based on either pseudo-steady state assumptions or the refined integral method indicate that the approximate solutions are very accurate when ACs is much larger than unity. However, as drug loading decreases, deviations between the approximate solutions and the exact solution increase so that the approximate solutions are least accurate in the limit ACs → 1.

50:50 Poly(d/-lactide-co-glycolide) (50:50 PLGA) was used to investigate the effects of polymer degradation on drug release from bulk degradable polymers. 5-Fluorouracil (5-FU) and Cyclosporin A (CyA) were used as model drugs. Using scanning electron microscopy, it was observed that initially non-porous 50:50 PLGA underwent significant morphological changes, becoming increasingly porous, as degradation proceeded. Concomitant increases in the transport parameters permeability and diffusivity of the model drugs through degrading 50:50 PLGA membranes were observed. Sharp transitions were observed in the relationship between the transport parameters and the residual polymer molecular weight and porosity—at values of molecular weight and porosity of about 5000–6000, and 70–80°, respectively. These transitions suggest that a shift in transport mechanism occurs with polymer degradation: the initial dominant transport pathway through degrading PLGA is the dense polymer phase, but as degradation progresses, the increase in porosity results in an increasingly connected pore structure such that, at some point in time, the pore network becomes the dominant pathway. By comparing experimentally measured 5-FU release profiles from PLGA matrices with release profiles calculated from experimentally measured permeability through degrading PLGA membranes containing no drug, it was shown that the shift in transport mechanism is the likely cause for the onset of the rapid final release stage of typical tri-modal release profiles from bulk-degradable polymer matrices.

The use of osmotic excipients to facilitate delivery of low dose protein drugs from nondegradable polymers was examined. The devices consist of particles of intimately mixed sodium chloride and a protein dispersed in an ethylene vinylacetate (EVA) polymer of 40% vinylacetate content. Protein and NaCl release results from osmotically induced membrane rupture of encapsulated particles subsequent to water imbibition. Using bovine serum albumin (BSA) as a model, the protein mass fraction in the particles was varied from 0.025 to 0.20. A critical value of protein mass fraction in the particle is defined, below which the cumulative mass fraction release rate of NaCl and protein are identical and above which the protein cumulative mass fraction release rate becomes slower than that of NaCl. This limit corresponds to protein saturation in the concentrated salt solution within the particle polymer surrounded capsules. Below this saturation limit, delivery profiles are protein-independent. Protein-independence was demonstrated with otherwise identical monoliths containing either BSA, lysozyme or epidermal growth factor.

Activated carbon (AC) and zerovalent iron (ZVI) have been widely used in the adsorption and dehalogenation process, respectively, for the removal of organic compounds in environmental treatments. This study aims to prepare ZVI/AC derived from an agricultural waste, coir pith, through simple one-step pyrolysis. The effect of activation temperature and time on the surface area, iron content, and zerovalent iron ratio of ZVI/AC was systemically investigated. The results indicated that the activation of AC by FeSO4 significantly increased surface area of AC and distributed elemental iron over the AC. The X-ray diffraction (XRD), electron spectroscopy for chemical analysis (ESCA), and X-ray absorption near edge structure (XANES) spectra of ZVI/AC revealed that zerovalent iron was present. As compared to AC without FeSO4 activation, ZVI/AC increased the trichloroethylene removal rate constant by 7 times. The dechlorination ability of ZVI/AC was dominated by the zerovalent iron content. We have shown that lab-made ZVI/AC from coir pith can effectively adsorb and dehalogenate the chlorinated compounds in water.

The purpose of this study was to develop a computational model to simulate the dynamics of intraocular gas behavior in pneumatic retinopexy (PR) procedure. The presented model predicted intraocular gas volume at any time and determined the tolerance angle within which a patient can maneuver and still gas completely covers the tear(s). Computational fluid dynamics calculations were conducted to describe PR procedure. The geometrical model was constructed based on the rabbit and human eye dimensions. SF6 in the form of pure and diluted with air was considered as the injected gas. The presented results indicated that the composition of the injected gas affected the gas absorption rate and gas volume. After injection of pure SF6, the bubble expanded to 2.3 times of its initial volume during the first 23 h, but when diluted SF6 was used, no significant expansion was observed. Also, head positioning for the treatment of retinal tear influenced the rate of gas absorption. Moreover, the determined tolerance angle depended on the bubble and tear size. More bubble expansion and smaller retinal tear caused greater tolerance angle. For example, after 23 h, for the tear size of 2 mm the tolerance angle of using pure SF6 is 1.4 times more than that of using diluted SF6 with 80% air. Composition of the injected gas and conditions of the tear in PR may dramatically affect the gas absorption rate and gas volume. Quantifying these effects helps to predict the tolerance angle and improve treatment efficiency.

Ethylene-co-vinyl acetate monoliths containing osmotic excipients of varying particle sizes and at various volume fractions were prepared. The excipients chosen were potassium chloride, sodium chloride, sodium salicylate, sodium phosphate monobasic, sodium carbonate and bovine serum albumin. The total fraction releasable was found to increase as the volumetric loading and the excipient osmotic activity increased, and was weakly inversely dependent on particle size. The total fraction released was enhanced by osmotic pressure induced polymer rupturing of encapsulated particles. A model was developed, based on the concept of a distribution of particle wall thicknesses around encapsulated particles in the monolith, and the existence of a critical wall thickness for rupture, to explain the fraction releasable enhancement. The model effectively explains the contribution of osmotic rupturing to the overall fraction releasable.

The mechanisms governing the release of osmotically active agents from hydrophobic polymeric monoliths are outlined. The release kinetics are loading dependent. Below the percolation threshold the bulk of the loaded excipient is released with zero order kinetics. Above the percolation threshold, diffusional and osmotic release mechanisms occur simultaneously resulting in a release profile that appears to be diffusionally controlled but whose slope increases with excipient osmotic activity. Current models explaining the observed zero order release rate are reviewed and their limitations outlined. A model was developed to overcome these limitations. The main parameters affecting release were determined to be the osmotic activity, saturation concentration and density of the incorporated agent, the tensile strength, elastic modulus and hydraulic permeability of the polymer and the fraction of particles released by dissolution and diffusion. The model was correlated against data from experiments and the literature and provided an excellent fit.

The fortification of salt with iron may greatly reduce the prevalence of iron deficiency globally, but fortification is complicated by iron-iodine interactions. To minimize this interaction, a spray dry microencapsulation system was developed. This study evaluates the creation and use of this system, producing engineered iron premixes for integration into coarse iodized salt. Bioavailable ferrous fumarate powders were encapsulated via spray-drying to produce particles which are too small to be detected visually (

Side chain liquid crystalline polysiloxane was synthesized and the effects of the DC electric field strength and the AC electric field frequency of an applied transmembrane field on membrane permeability were investigated. In this paper, the synthesis method of poly(methyl p-propyloxyphenyl, p-methoxy benzoate siloxane) and permeation data of p-aminoacetophenone through this polymer at 5°C are presented. Membrane permeability was observed to increase with increasing field strength and decrease with increasing frequency. Utilizing DC electric field, 28-fold increase in membrane permeability was obtained with a field strength of 4,200 V/cm. At a field strength of 4,900 V/cm, a 26-fold range in permeation rate was obtained between 0.001 Hz and 10 KHz. The response times required to achieve new steady state fluxes after changing frequency at 4,900 V/cm were observed to be nearly instantaneous in contrast to those observed on changing the DC electric field strength.

The primary route into the eye for many drugs is transcorneal permeation. A better understanding of the mechanisms involved in transcorneal permeation could lead to improvements in drug dosage forms or the development of drug delivery devices which enhance the ocular bioavailability of drugs. A corneal permeation model has been developed which can be used to study the mechanisms involved in corneal permeation. The model uses five compartments in series to simulate the tear film, epithelium, stroma, endothelium and aqueous humour. These tissues were assumed to be adequately represented by plane sheet barriers of physiological thickness. The tear film was assumed to be perfectly mixed and the stroma completely stagnant. Due to inadequate knowledge of the hydrodynamics of the aqueous humour, both stagnant and perfectly mixed extremes were studied. The four routes of drug loss which were considered the most significant and therefore included in the model were lacrimal drainage, conjunctival absorption, aqueous drainage and iris-ciliary body absorption. The equilibrium that can exist between the ionic and non-ionic forms of a drug was found to be an important step in the mechanism of transcorneal permeation. Including the equilibrium condition in the model resulted in aqueous humour drug levels that were over 50 times higher than the levels predicted by a model which did not use the equilibrium mechanism. A relationship between the lipophilicity of each of the two drug forms and its permeability in each layer of the cornea was used in the model. The model was used to predict aqueous humour drug concentrations resulting from a constant release of timolol into the tear film or from the application of timolol, levobunolol and pilocarpine eyedrops. The model produced transient aqueous humour drug levels that closely followed experimental in vivo data from literature. Using the model, it was also possible to predict the amount of instilled drug that is lost through each of the four elimination routes of the eye.

The objective of this study was to evaluate the solubility of lead from various lead salts and vitrified slagged aggregate (VSA) in aqueous solutions.

Protein phosphatase 2A (PP2A) is a ubiquitous phospho-serine/threonine phosphatase that controls many diverse cellular functions. The predominant form of PP2A is a heterotrimeric holoenzyme consisting of a scaffolding A subunit, a variable regulatory B subunit, and a catalytic C subunit. The C subunit also associates with other interacting partners, such as α4, to form non-canonical PP2A complexes. We report visualization of PP2A complexes in mammalian cells. Bimolecular fluorescence complementation (BiFC) analysis of PP2A subunit interactions demonstrates that the B subunit plays a key role in directing the subcellular localization of PP2A, and confirms that the A subunit functions as a scaffold in recruiting the B and C subunits to form a heterotrimeric holoenzyme. BiFC analysis also reveals that α4 promotes formation of the AC core dimer. Furthermore, we demonstrate visualization of specific ABC holoenzymes in cells by combining BiFC and fluorescence resonance energy transfer (BiFC-FRET). Our studies not only provide direct imaging data to support previous biochemical observations on PP2A complexes, but also offer a promising approach for studying the spatiotemporal distribution of individual PP2A complexes in cells.

OBJECTIVE: To develop a temperature-responsive polymer membrane that is permeable to drug only at temperatures above 42oC. A triggerable implant that releases drug only when heated can be made by encapsulating a drug reservoir with such a thermoresponsive membrane. Such an implant can be applied in clinical situations in which it is desirable to release drug only on demand, such as erectile dysfunction. METHODS: A porous polyethylene (PE) membrane was modified by fillings its pores with either docosane or a docosane:eicosane mixture. The melting transition of the alkanes corresponds to a diffusional switch, thus, the alkane melting point corresponds to the membrane release trigger temperature. The onset of melting for each alkane and the alkane mixture was measured by differential scanning calorimetry. Using a diffusion cell, the permeability of propranolol hydrochloride (PRO) through the thermoresponsive membrane was measured. RESULTS: PRO permeation through the docosane-absorbed PE membrane at 37oC and 45oC was reversible, and was reproducible after five cycles of temperature oscillation. From an aqueous solution reservoir, the ratio of PRO permeability through the docosane-absorbed PE membrane at 45oC versus 37oC was 378±65. Similarly, the ratio of PRO permeability through the docosane:eicosane (90:10) PE membrane at 42.5oC and at 37oC was 235±56. CONCLUSIONS: The high on/off permeability ratio achieved with PRO provides promise for the development of a thermoresponsive implant by using this membrane and a suitable drug. Local heating of the implant may be achieved by external power sources such as ultrasonic or microwave heaters.

The purpose of this study was to determine how the position and volume of an intravitreal injection affect the distribution and elimination of drug from the vitreous humor.A mathematical model that had been developed and used previously to study drug distribution in the vitreous humor of the rabbit eye was modified to match the physiology of the human eye. Fluorescein and fluorescein glucuronide were used as the model compounds for these studies. Four extreme injection locations were considered: a central injection, an injection displaced towards the retina, an injection displaced towards the lens, and an injection displaced toward the hyaloid membrane. Injections containing an equal mass of drug dissolved in volumes of either 15 microL or 100 microL were compared.The location of an intravitreal injection was found to have a substantial effect on elimination and distribution in the vitreous. Peak concentrations at different vitreous locations varied by over three orders of magnitude, depending on the injection location. The mean concentration of drug remaining in the vitreous 24 hours after the intravitreal injection varied by up to a factor of 3.8, depending on the injection location. Changing the volume of the injection from 15 microL to 100 microL dampened the effects of the initial injection location; however, meant concentrations at 24 hours still varied by up to a factor of 2.5.Careful control of the conditions of an intravitreal injection could reduce treatment variability, improve bioavailability, and reduce the possibility of retinal toxicity.

Three of the five hypervariable domains (V1-V3) of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 have previously been shown to be dispensable for antigenic epitopes recognized by broadly neutralizing monoclonal antibodies. In this study, the influence of the V4 and V5 domains on an epitope recognized by a broadly neutralizing human monoclonal antibody, 1.5e, was investigated. In contrast with the V1, V2, and V3 domains of gp120, the V4 and V5 domains were found to be critical for binding to both CD4 and 1.5e. Our results suggest that V4 and V5 are in structurally less flexible regions of gp120 than V1, V2, and V3 and raises the question of whether variable domains V4 and V5 are also indispensable for other broadly neutralizing antibodies in the same class as 1.5e.

Human monoclonal antibody 2.3a was previously shown to enhance human immunodeficiency virus type 1 (HIV-1) infection in vitro. This enhancing antibody recognizes a conserved epitope of envelope glycoprotein gp120. We report here that binding of the 2.3a antibody to gp120 is significantly affected by deletions of certain N- or C-terminal residues of gp120. However, not all such deletions affect the epitope recognized by a broadly neutralizing human monoclonal antibody, 1.5e. These findings suggest the feasibility of designing a gp120 antigen that is free of 2.3a epitope while retaining the conformation of the 1.5e epitope.

Total internal reflection fluorescence (TIRF) is used to examine the adsorption of bovine serum albumin (BSA) and bovine fibrinogen on crosslinked polydimethylsiloxane (silicone rubber) surfaces from flowing solutions. By comparing experimentally observed adsorption rates with the predictions of a convection/diffusion model, it is shown that the adsorption of both BSA and fibrinogen on silicone rubber is diffusion-controlled over the range of solution concentrations (0.01

Total internal reflection fluorescence (TIRF) is a technique that may be used to examine the interaction of macromolecules with solid surfaces. In this report, a TIRF apparatus and its application to the adsorption of proteins from flowing solutions on polymer films are described. Bovine serum albumin (BSA)/crosslinked polydimethylsiloxane (silicone rubber) is the protein/surface pair considered herein. To relate TIRF fluorescence signals to actual surface concentrations, a calibration technique using BSA labeled with both tritium and fluorescein isothiocyanate (FITC) was developed. Unambiguous calibration results require a linear relationship between observed fluorescence intensity and protein surface concentration, reproducible evanescent field intensities, and constant fluorescence quantum efficiencies. The contribution of bulk solution fluorescence to the total TIRF signal must be ascertained to ensure accurate quantitative interpretation of TIRF data. There are two sources of solution fluorescence: one arising from excitation of fluorescent solution protein by scattered light, the second from solution protein within the evanescent field. Solution protein within the evanescent field is distinguished from reversibly adsorbed proteins by comparing its exchange dynamics with that of nonadsorbing FITC-dextran together with the predictions of a hydrodynamic model. By removing the solution protein contributions to the total TIRF signal, surface-adsorbed protein fluorescence, and thus the amount of protein adsorbed, can be obtained. Bulk solution contribution to the total TIRF signal increases with solution concentration. Experiments were conducted at solution concentrations of 2 and 200 mg%, both corresponding to an equilibrium surface concentration of 0.14 μg/cm 2 , the saturated surface concentrations for BSA adsorbing on silicone rubber. Proteins in the 2 mg% solution contributed negligibly to the total fluorescence, while fluorescence from the 200 mg% solution constituted a significant fraction of the total TIRF signal.

Total internal reflection fluorescence is used to examine the initial adsorption, desorption, and exchange kinetics of the protein bovine serum albumin (BSA) on six polymer surfaces with widely varying surface properties and functionalities. The six surfaces studied are polydimethylsiloxane (PDMS), polydiphenylsiloxane (PDϕS), polycyanopropylmethylsiloxane (PCPMS), polymethyl methacrylate (PMMA), polystyrene sulfonate (PSS), and polyethylene oxide (PEO). The results show that the initial adsorption of BSA on the surfaces PDMS, PDϕS, and PCPMS is diffusion limited up to wall shear rates of 4000 s −1 . The initial adsorption of BSA on PSS is diffusion limited at shear rates below about 70 s −1 but becomes kinetically controlled at higher shear rates. BSA adsorption on PMMA is kinetically controlled, and the adsorption of BSA on PEO is too slow to be detected under the conditions used. Studies on the kinetically limited BSA adsorption onto PMMA show that the adsorption process can be described by a kinetic rate expression that is first order in protein concentration. The initial desorption of BSA adsorbed onto each surface (except PEO) is shown to be kinetically limited. The rate-limiting step for the exchange of BSA adsorbed onto PDMS is shown to be the desorption of adsorbed BSA.