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Biomedical subjects

J G Weers

Publications and source records attributed to J G Weers.

9 recordsLinked to original sources
PubMed2000

Hollow porous particles in metered dose inhalers.

PURPOSE: To assess the physical stability and aerosol characteristics of suspensions of hollow porous microspheres (PulmoSpheres) in HFA-134a. METHODS: Cromolyn sodium, albuterol sulfate, and formoterol fumarate microspheres were prepared by a spray-drying method. Particle size and morphology were determined via electron microscopy. Particle aggregation and suspension creaming times were assessed visually, and aerosol performance was determined via Andersen cascade impaction and dose uniformity studies. RESULTS: The hollow porous particle morphology allows the propellant to permeate freely within the particles creating a novel form of suspension termed a homodispersion, wherein the dispersed and continuous phases are identical, separated by an insoluble interfacial layer of drug and excipient. Homodispersion formation improves suspension stability by minimizing the difference in density between the particles and the medium, and by reducing attractive forces between particles. The improved physical stability leads to excellent dose uniformity. Excellent aerosolization efficiencies are also observed with PulmoSpheres formulations, with fine particle fractions of about 70%. CONCLUSIONS: The formation of hollow porous particles provides a new formulation technology for stabilizing suspensions of drugs in hydrofluoroalkane propellants with improved physical stability, content uniformity, and aerosolization efficiency.

Administration, Inhalation↗
PubMed2000

Novel lipid-based hollow-porous microparticles as a platform for immunoglobulin delivery to the respiratory tract.

PURPOSE: Delivery of specific antibodies or immunoglobulin constructs to the respiratory tract may be useful for prophylaxis or active treatment of local or systemic disorders. Therefore, we evaluated the utility of lipid-based hollow-porous microparticles (PulmoSpheres) as a potential delivery vehicle for immunoglobulins. METHODS: Lipid-based microparticles loaded with human immunoglobulin (hIgG) or control peptide were synthesized by spray drying and tested for: i) the kinetics of peptide/protein release, using ELISA and bioassays; ii) bioavailability subsequent to nonaqueous liquid instillation into the respiratory tract of BALB/c mice, using ELISA and Western blotting; iii) bioactivity in terms of murine immune response to xenotypic epitopes on human IgG, using ELISA and T cell assays; and iv) mechanisms responsible for the observed enhancement of immune responses, using measurement of antibodies as well as tagged probes. RESULTS: Human IgG and the control peptide were both readily released from the hollow-porous microspheres once added to an aqueous environment, although the kinetics depended on the compound. Nonaqueous liquid instillation of hIgG formulated in PulmoSpheres into the upper and lower respiratory tract of BALB/c mice resulted in systemic biodistribution. The formulated human IgG triggered enhanced local and systemic immune responses against xenotypic epitopes and was associated with receptor-mediated loading of alveolar macrophages. CONCLUSIONS: Formulation of immunoglobulins in hollow-porous microparticles is compatible with local and systemic delivery via the respiratory mucosa and may be used as means to trigger or modulate immune responses.

Administration, Inhalation↗
PubMed1994

Fluorocarbon emulsions--the stability issue.

Long-term room temperature stability of ready-to-use concentrated fluorocarbon emulsions is necessary in order to fully exploit the therapeutic potential of fluorocarbons. Consequently, considerable efforts have been directed at investigating the physical nature of such emulsions, the mechanisms which lead to their degradation and the means of counteracting these. The particles which constitute typical fluorocarbon/egg yolk phospholipid emulsions have been identified to be surfactant-coated fluorocarbon droplets and lipid vesicles. Better understanding has been gained on the formation, structure and evolution of these particles during processing and storage. This has led to optimized formulations and processing, better control of emulsion characteristics and significantly improved stability. Molecular diffusion (Ostwald ripening or transcondensation) has been shown to be the maun mechanism of degradation when particles are less than 1 micron in diameter, even for the highly concentrated (volume fraction of fluorocarbon up to 50%) second generation fluorocarbon emulsions. Significant emulsion stabilization has been accomplished by adding fluorochemicals which are both less volatile and less water soluble, and nevertheless have an organ dwell time acceptable for intravascular use. The rate of molecular diffusion can also be reduced by decreasing the fluorocarbon/water interfacial tension; this was effectively achieved with appropriate, well-defined fluorinated surfactants. A further, novel means of stabilizing fluorocarbon-in-water emulsions makes use of mixed fluorocarbon-hydrocarbon amphiphiles which act as molecular dowels to reinforce the adhesion between the fluorocarbon phase and the lipophilic zone of the surfactant film. Both long-term room temperature stability, and particle-size control over a large range of diameter, have been achieved by applying this principle. All in all it can be said that the challenge of producing injectable fluorocarbon emulsions with long-term room temperature particle size stability has been met.

Blood Substitutes↗
PubMed1994

Influence of perflubron emulsion particle size on blood half-life and febrile response in rats.

Perfluorochemical (PFC) emulsions are particulate in nature and, as such, can cause delayed febrile reactions when injected intravenously. This study investigated the influence of emulsion particle size on intravascular retention and on body temperature changes in unrestrained conscious rats. Concentrated (60% to 90% w/v) emulsions based on perflubron (perfluorooctyl bromide [PFOB]) with mean particle sizes ranging from 0.05 microns to 0.63 microns were tested. Rats were fitted with a chronic jugular catheter and an abdominal body temperature telemetry unit. Fully recovered, conscious rats were monitored for 24 hours after infusion (dose = 2.7 g PFC/kg). Emulsion blood half-life (T1/2) was determined from blood perflubron levels measured by gas chromatography. Emulsions with a particle size of 0.2-0.3 microns caused fevers (6 to 8 hour duration) which peaked at 1-1.5 degrees C above normal (approximately 37.5 degrees C). Fevers could be blocked by i.v. treatment with either cyclooxygenase inhibitors (ibuprofen) or corticosteroids (dexamethasone). Both intensity and duration of the temperature response, quantified by area under the temperature curve, was decreased significantly for emulsions with a particle size < or = 0.12 micron. Blood T1/2 varied inversely with particle size, and was 3 to 4 fold longer for emulsions with a mean particle size < or = 0.2 micron. Thus, smaller emulsion particles more effectively evaded the reticuloendothelial system, which resulted in longer intravascular retention, less macrophage activity, and reduced febrile responses.

Animals↗
PubMed1994

Room temperature stable perfluorocarbon emulsions with acceptable half-lives in the reticuloendothelial system.

Prolonged room temperature stability (i.e. zero particle growth) can be achieved for concentrated emulsions of perflubron (perfluorooctyl bromide) or perfluorodecalin via addition of a secondary high molecular weight, lipophilic fluorocarbon component. Due to their enhanced lipophilic character, the secondary fluorocarbon components have acceptable half-lives in the organs of the reticuloendothelial system.

Animals↗
PubMed1992

Stabilization of perflubron emulsions with egg yolk phospholipid.

Egg Yolk Phospholipid(EYP) has been used extensively as the primary surfactant in parenteral fat emulsions for many years. The simplicity, functionality and physiologic tolerance of EYP has contributed greatly to its success in the intravenous emulsion arena. The mechanism of stabilization in triglyceride emulsions is well understood; however, this is not the case with perfluorocarbon emulsions. Interfacial models, as well as emulsion stability studies, have been conducted utilizing EYP of varied composition in order to derive a structure/function relationship. Our studies indicate that minor components, total unsaturation, acyl chain length and presence of charged species have significant impact on the functional properties of EYP and the subsequent stability of the emulsion product. These findings contribute to our ability to design and manipulate natural surfactants with superior properties for use in medical applications of perfluorocarbon emulsions.

Blood Substitutes↗
PubMed1986

Triplet-singlet energy transfer in the complex of auramine O with horse liver alcohol dehydrogenase.

Triplet-singlet energy transfer has been studied in the complex formed between auramine O (AO) and horse liver alcohol dehydrogenase with optically detected magnetic resonance (ODMR) spectroscopy. The results show that Trp-15 and Tyr residues transfer triplet energy mainly by a trivial process, whereas Trp-314 transfers triplet energy by a Förster process with two observed lifetimes at 77 K of 170 and 50 ms. The different Förster energy-transfer lifetimes are ascribed either to quenching of the two Trp-314 residues of the dimer by a single asymmetrically bound AO or to two distinct conformations of the enzyme-dye complex with differing separations and/or orientations of donor and acceptor. Individual spin sublevel transfer rate constants are reported for the major decay component with the 170-ms Trp triplet-state lifetime; these are found to be highly selective with kxtr much greater than kytr and kztr.

Alcohol Dehydrogenase↗