Mechanisms of burst release from pH-responsive polymeric microparticles.

Microencapsulation of drugs into preformed polymers is commonly achieved through solvent evaporation techniques or spray drying. We compared these encapsulation methods in terms of controlled drug release properties of the prepared microparticles and investigated the underlying mechanisms responsible for the “burst release” effect. Using two different pH-responsive polymers with a dissolution threshold of pH 6 (Eudragit L100 and AQOAT AS-MG), hydrocortisone, a model hydrophobic drug, was incorporated into microparticles below and above its solubility within the polymer matrix. Although, spray drying is an attractive approach due to rapid particle production and relatively low solvent waste, the oil-in-oil microencapsulation method is superior in terms of controlled drug release properties from the microparticles. Slow solvent evaporation during the oil-in-oil emulsification process allows adequate time for drug and polymer redistribution in the microparticles and reduces uncontrolled drug burst release. Electron microscopy showed that this slower manufacturing procedure generated non-porous particles whereas thermal analysis and X-ray diffractometry showed that drug loading above the solubility limit of the drug in the polymer generated excess crystalline drug on the surface of the particles. Raman spectral mapping illustrated that drug was homogeneously distributed as a solid solution in the particles when loaded below saturation in the polymer with consequently minimal burst release

The Chemical and Ionization Conditions in Weak Mg II Absorbers

We present an analysis of the chemical and ionization conditions in a sample of 100 weak Mg II absorbers identified in the VLT/UVES archive of quasar spectra. Using a host of low ionization lines associated with each absorber in this sample, and on the basis of ionization models, we infer that the metallicity in a significant fraction of weak Mg II clouds is constrained to values of solar or higher, if they are sub-Lyman limit systems. Based on the observed constraints, we present a physical picture in which weak Mg II absorbers are predominantly tracing two different astrophysical processes/structures. A significant population of weak Mg II clouds, those in which N(Fe II) is much less than N(Mg II), identified at both low (z ~ 1) and high (z ~ 2) redshift, are potentially tracing gas in the extended halos of galaxies, analogous to the Galactic high velocity clouds. These absorbers might correspond to alpha-enhanced interstellar gas expelled from star-forming galaxies, in correlated supernova events. On the other hand, N(FeII) approximately equal to N(Mg II) clouds, which are prevalent only at lower redshifts (z < 1.5), must be tracing Type Ia enriched gas in small, high metallicity pockets in dwarf galaxies, tidal debris, or other intergalactic structures.Comment: 35 pages (including tables & figures). Accepted for publication in ApJ. A high resolution version of the paper is available at "http://www.astro.wisc.edu/~anand/weakMgII.pdf

Using pH abnormalities in diseased skin to trigger and target topical therapy

Abstract Purpose: The pH discrepancy between healthy and atopic dermatitis skin was identified as a site specific trigger for delivering hydrocortisone from microcapsules. Methods: Using Eudragit L100, a pH-responsive polymer which dissolves at pH 6, hydrocortisone-loaded microparticles were produced by oil-in-oil microencapsulation or spray drying. Release and permeation of hydrocortisone from microparticles alone or in gels was assessed and preliminary stability data was determined. Results: Drug release from microparticles was pH-dependent though the particles produced by spray drying also gave significant non-pH dependent burst release, resulting from their porous nature or from drug enrichment on the surface of these particles. This pH-responsive release was maintained upon incorporation of the oil-in-oil microparticles into Carbopol- and HPMC-based gel formulations. In-vitro studies showed 4 to 5-fold higher drug permeation through porcine skin from the gels at pH 7 compared to pH 5. Conclusions: Permeation studies showed that the oil-in-oil generated particles deliver essentially no drug at normal (intact) skin pH (5.0 – 5.5) but that delivery can be triggered and targeted to atopic dermatitis skin where the pH is elevated. The incorporation of these microparticles into Carbopol- and HPMC-based aqueous gel formulations demonstrated good stability and pH-responsive permeation into porcine skin

The role of lipid composition on the interaction between a tryptophan-rich protein and model bacterial membranes

The interaction between tryptophan-rich puroindoline proteins and model bacterial membranes at the air-liquid interface has been investigated by FTIR spectroscopy, surface pressure measurements and Brewster angle microscopy. The role of different lipid constituents on the interactions between lipid membrane and protein was studied using wild type (Pin-b) and mutant (Trp44 to Arg44 mutant, Pin-bs) puroindoline proteins. The results show differences in the lipid selectivity of the two proteins in terms of preferential binding to specific lipid head groups in mixed lipid systems. Pin-b wild type was able to penetrate mixed layers of phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) head groups more deeply compared to the mutant Pin-bs. Increasing saturation of the lipid tails increased penetration and adsorption of Pin-b wild type, but again the response of the mutant form differed. The results provide insight as to the role of membrane architecture, lipid composition and fluidity, on antimicrobial activity of proteins. Data show distinct differences in the lipid binding behavior of Pin-b as a result of a single residue mutation, highlighting the importance of hydrophobic and charged amino acids in antimicrobial protein and peptide activity

I am Cuba-Soy Cuba: Commemorating 100 years of Russian Revolution

I am Cuba Soy Cuba is a 1964 Soviet Cuban film directed by Mikhail Kalatozov Hidden away in the Soviet archives for three decades, I Am Cuba is a wild celebration of Communist kitsch, mixing Slavic solemnity with Latin sensuality — a whirling, feverish dance through both the sensuous decadence of pre-revolutionary Havana and the grinding poverty and oppression of the Cuban people. In four stories of the revolution, the camera takes the viewer on a rapturous roller-coaster ride of bathing beauties, landless peasants, fascist police, and student revolutionaries.https://digitalcommons.fiu.edu/cri_events/1370/thumbnail.jp

Selected wheat seed defense proteins exhibit competitive binding to model microbial lipid interfaces

Puroindolines (Pins) and purothionins (Pths) are basic, amphiphilic, cysteine-rich wheat proteins that play a role in plant defense against microbial pathogens. We have examined the co-adsorption and sequential addition of Pins (Pin-a, Pin-b and a mutant form of Pin-b with Trp-44 to Arg-44 substitution) and β-purothionin (β-Pth) model anionic lipid layers, using a combination of surface pressure measurements, external reflection FTIR spectroscopy and neutron reflectometry. Results highlighted differences in the protein binding mechanisms, and in the competitive binding and penetration of lipid layers between respective Pins and β-Pth. Pin-a formed a blanket-like layer of protein below the lipid surface that resulted in the reduction or inhibition of β-Pth penetration of the lipid layer. Wild-type Pin-b participated in co-operative binding with β-Pth, whereas the mutant Pin-b did not bind to the lipid layer in the presence of β-Pth. The results provide further insight into the role of hydrophobic and cationic amino acid residues in antimicrobial activity

Person-Centredness In the Workplace: An Examination of Person-Centred Skills, Processes and Workplace Factors Among Medicaid Waiver Providers In the United States

Background: Existing research supports the effectiveness of person-centred practices in working with persons with physical, intellectual and developmental disabilities, but less clear is the influence of workplace factors on the implementation and quality of person-centred practices. Aims: This article explores the influence of workplace factors on job satisfaction and on the implementation and quality of person-centred practices in healthcare agencies that provide home- and community-based services through a Medicaid waiver in Mississippi, a state in the southeastern United States. Methods: Purposive sampling was used to collect data via online surveys to explore the interrelationships among person-centred workplaces, job satisfaction and person-centred practices. Results: Path analysis reveals that a person-centred workplace influences both skill implementation and person-centred processes. Job satisfaction was significantly correlated to skill implementation and person-centred processes in bivariate analysis but was not detected in the path model. Conclusion: This study suggests that organisations may improve the provision of person-centred practices by investing in policies that create a person-centred workplace

Interactions between Hydrolysable Tannins and Lipid Vesicles from Escherichia coli with Isothermal Titration Calorimetry

Isothermal titration calorimetry (ITC) was used to study the interactions between hydrolysable tannins (HTs) and lipid vesicles prepared from a phospholipid extract of Escherichia coli (E. coli). A group of 24 structurally different HTs was selected, and structural differences affecting their affinities to interact with lipid vesicles in aqueous buffered media were identified. In general, the interactions between HTs and lipid vesicles were exothermic in nature, and ITC as a technique functioned well in the screening of HTs for their affinity for lipids. Most notably, the galloyl moiety, the structural flexibility of the entire tannin structure, the hydrophobicity of the tannin, and higher molecular weight were observed to be important for the stronger interactions with the lipids. The strongest interactions with lipids were observed for rugosins D and G. It was also observed that some HTs with moderate hydrophobicities, such as geraniin, chebulagic acid, and chebulinic acid, did not have any detectable interactions with the lipid vesicles, suggesting that a hydrophobic structure alone does not guarantee an affinity for lipids.</p

Interactions between Hydrolysable Tannins and Lipid Vesicles from Escherichia coli with Isothermal Titration Calorimetry

Isothermal titration calorimetry (ITC) was used to study the interactions between hy- drolysable tannins (HTs) and lipid vesicles prepared from a phospholipid extract of Escherichia coli (E. coli). A group of 24 structurally different HTs was selected, and structural differences affecting their affinities to interact with lipid vesicles in aqueous buffered media were identified. In general, the interactions between HTs and lipid vesicles were exothermic in nature, and ITC as a technique functioned well in the screening of HTs for their affinity for lipids. Most notably, the galloyl moiety, the structural flexibility of the entire tannin structure, the hydrophobicity of the tannin, and higher molecular weight were observed to be important for the stronger interactions with the lipids. The strongest interactions with lipids were observed for rugosins D and G. It was also observed that some HTs with moderate hydrophobicities, such as geraniin, chebulagic acid, and chebulinic acid, did not have any detectable interactions with the lipid vesicles, suggesting that a hydrophobic structure alone does not guarantee an affinity for lipids