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E Sponsler

Publications and source records attributed to E Sponsler.

5 recordsLinked to original sources
PubMed1995

Preservation of surface-dependent properties of viral antigens following immobilization on particulate ceramic delivery vehicles.

B-cell stimulation for the purpose of evoking an effective neutralizing humoral immune response is a surface phenomenon that is exquisitely specific to antigen conformation. Consequently, successful delivery of antigen, such as would be desired in a vaccine, entails preservation of an antigen's apparent native surface (conformational) properties. Prior to testing the actual vaccinating efficacy of delivered antigens, the surface properties could be assessed through a variety of in vitro and in vivo assays in which the measurement standard would be the properties of the antigens in their native state (whole virus). Using surface modified nanocrystalline carbon and calcium-phosphate ceramic particulates (carbon ceramics and brushite), we evaluated the surface activity of immobilized non-nuclear material extracted from HIV-1. Physical characterization showed that the particles with immobilized antigen ("HIV decoys") measured 50 nm in diameter (HIV = 50-100 nm) and exhibited the same zeta potentials as whole (live) HIV. In vitro testing showed that the HIV decoys were recognized by both conformationally nonspecific and specific monoclonal antibodies, were recognized by human IgG from HIV antibody-positive patients, and could promote surface agglomeration among malignant T-cells similar to live HIV. Last, in vivo testing in three vaccinated animal species showed that the HIV decoys elicited humoral and cellular immune responses similar to that evoked by whole (live) HIV.

Animals↗
PubMed1994

Cross linking encapsulated hemoglobin with solid phase supports: lipid enveloped hemoglobin adsorbed to surface modified ceramic particles exhibit physiological oxygen lability.

To reduce hemoglobin toxicity, a cross linking agent is generally used. To preserve hemoglobin function, an allosteric modifier is generally used. Historically, the use of one has precluded the use of the other. A potential solution to this problem was investigated. Hemoglobin AO was adsorbed irreversibly to carbohydrate coated nanosized diamond particles and then encapsulated in a standard mixture of phospholipids. Endotoxin free preparations with concentrations of bound hemoglobin near 10 g/dl were achieved with as little as 0.1 g/dl of free hemoglobin and remained stable over a 48 hour period. By transmission electron microscopy these particles appeared roughly spherical and measured approximately 75 nanometers well below that of alveolar capillary vessels. In shallow pH gradients, liquid electrophoresis demonstrated that such constructs exhibit Bohr effect behavior by the induction of a dramatic surface charge inversion at around pH 6.8. To evaluate oxygen lability, oxygen saturation trials were conducted in isosmolar physiological salts. Normal sigmoidal binding behavior of O2 over a typical pO2 gradient could be modulated by systemic levels of pyridoxyl-5-phosphate. Constructs with a P50 as low as 12 mm Hg could be increased to 37 mm Hg with the allosteric effector. Viscosity and bio distribution studies are to follow. The use of solid phase nanocrystalline supports to cross link hemoglobin may reduce the toxicity of free hemoglobin while still enabling the use of allosteric modifiers.

Adsorption↗
PubMed1992

Sterically stabilized liposomes. Reduction in electrophoretic mobility but not electrostatic surface potential.

The electrophoretic mobility of liposomes containing a negatively charged derivative of phosphatidylethanolamine with a large headgroup composed of the hydrophilic polymer polyethylene glycol (PEG-PE) was determined by Doppler electrophoretic light scattering. The results show that this method is improved by the use of measurements at multiple angles to eliminate artifacts and that very small mobilities can be measured. The electrophoretic mobility of liposomes with 5 to 10 mol% PEG-PE is approximately -0.5 mu ms-1/Vcm-1 regardless of PEG-PE content compared with approximately -2 mu ms-1/Vcm-1 for similar liposomes but containing 7.5% phosphatidylglycerol (PG) instead of PEG-PE. Measurements of surface potential by distribution of an anionic fluorescent probe show that the PEG-PE imparts a negative charge identical to that by PG, consistent with the expectation of similar locations of the ionized phosphate responsible for the charge. The reduced mobility imparted by the surface bound PEG is attributed to a mechanism similar to that described for colloidal steric stabilization: hydrodynamic drag moves the hydrodynamic plane of shear, or the hydrodynamic radius, away from the charge-bearing plane, that of the phosphate moities. An extended length of approximately 50 A for the 2,000 molecular weight PEG is estimated from the reduction in electrophoretic mobility.

Biophysical Phenomena↗
PubMedDate not supplied

Drug delivery systems for the future.

Parenteral drug delivery systems have the potential to make drugs both safer and more effective. While research in this field has been active for over 30 years, the current fiscal constraints of health care delivery add a greater degree of urgency to finding a working system. The three competing technologies currently under development include prodrug or zymogen-like systems, simple soluble macromolecular systems, and complex particulate multicomponent systems. In this review, the advantages, disadvantages, and areas for further development of these three basic technology systems are compared and contrasted; the biophysical constraints are considered; and a model solution system using surface modified nanocrystalline ceramics is described.

Antibodies, Monoclonal↗