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Biomedical subjects

T J Pelura

Publications and source records attributed to T J Pelura.

10 recordsLinked to original sources
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

Oxidative assessment of phospholipid-stabilized perfluorocarbon-based blood substitutes.

Methods based on the HPLC separation with subsequent UV detection and spectrofluorimetry have been developed to monitor the formation of oxidative decomposition products of phospholipids in perfluorocarbon emulsions. Catalytic, as well as emulsion oxidative stability studies have been conducted utilizing egg yolk phospholipid (EYP) and perfluorocarbons of varied compositions/purity in order to assess their effect on susceptibility to oxidation. Our studies indicate that phospholipid composition, degree of unsaturation, perfluorocarbon purity and the presence of oxygen and trace metals have a significant effect on the formation of oxidative decomposition products. A combination of methods has proven useful in monitoring the levels of oxidative decomposition products of phospholipids in phospholipid-stabilized perfluorocarbon-based blood substitutes. Such an approach has proven beneficial in the development of pharmaceutical agents of potentially higher quality and storage stability.

Blood Substitutes↗
PubMed1994

Effects of buffer pH and phosphate concentration on the droplet size and EYP hydrolysis of perflubron/EYP emulsions.

Oil-in-water emulsions containing perflubron (perfluorooctyl bromide; PFOB) and stabilized with egg yolk phospholipid (EYP) have potential applications as contrast agents and oxygen carriers. In this study, the effects of buffer pH and total phosphate concentration on the emulsion droplet size and EYP hydrolysis were evaluated. 90% w/v perflubron emulsions with NaH2PO4-Na2HPO4 buffers of different pH (4.7-8.7) and phosphate concentrations (30 and 60 mM) were prepared with a high-pressure homogenizer. Emulsions were stored at 40 degrees C and tested at 0, 1, 2 and 3 months. The pH dropped quickly in emulsions with pH 8.7 buffer whereas acidic and neutral buffered emulsions exhibited minor pH drops. The concentration of free fatty acids (FFA) vs emulsion pH can be fitted to a parabolic curve with a minimum at about pH 6.0. The droplet growth rates in emulsions with the pH 4.7 buffer were about 2.5 times of those in emulsions with the pH 8.7 buffer. Total phosphate concentration had only a minor effect. This study emphasizes the importance of the careful selection of buffer pH and capacity to control EYP hydrolysis and possibly emulsion droplet size.

Buffers↗
PubMed1994

Effects of formulation, processing and storage parameters on the characteristics and stability of perflubron emulsion.

In this study, the effects of formulation, processing and storage parameters on perflubron (perfluorooctyl bromide; PFOB) emulsions were investigated. Emulsions with varying concentrations of perflubron and egg yolk phospholipid (EYP) were prepared with different processing parameters and placed at different storage temperatures. Their characteristics and stability were compared. The emulsion droplet growth rate was nearly proportional to the perflubron percentage in the range of 15-110% w/v. The initial droplet size of perflubron emulsions was inversely proportional to the concentration of EYP until a certain lower limit of droplet size was reached. The initial droplet size and droplet growth rate of perflubron emulsion were strongly dependent upon the processing parameters. The logarithmic value of the droplet growth rate decreased linearly with l/T in the range of 5-40 degrees C. The formulation and processing parameters are the key variables to be optimized to achieve better emulsion characteristics and stability.

Drug Stability↗
PubMed1992

Development of highly fluid, concentrated and stable fluorocarbon emulsions for diagnosis and therapy.

A challenging aim in developing injectable fluorocarbon emulsions is to combine good flow characteristics (especially at low shear rates) with the high fluorocarbon concentration required for high oxygen delivery or effective contrast in imaging, long shelf life, and biological acceptability. A good balance of these sometimes conflicting objectives has been achieved with 90% w/v concentrated emulsions of various fluorocarbons, including the radiopaque oxygen carrier perfluorooctylbromide (PFOB, perflubron). The sterile emulsions have viscosities of about 20 cPs at a shear rate of 1 sec-1; the viscosity decreases rapidly with fluorocarbon concentration, and at 60% w/v the viscosity is less than that of human blood. The emulsions are suitable for injection as prepared, and are stable unfrozen for over a year.

Blood Substitutes↗
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↗
PubMed1992

Drop size stability assessment of fluorocarbon emulsions.

The aging of fluorocarbon emulsions prepared with natural egg yolk phospholipids (EYP) has been studied and a linear variation (r2 greater than 0.95) of the mean average volume of the droplets with time has been observed. The slope of the experimental lines, called "Stability Parameter, S" can thus be taken as a representation of the rate of aging of the emulsions. Examples are given of use of parameter S to assess the effect of formulation and processing parameters on the stability of diverse fluorocarbon emulsions. S is a useful tool to compare emulsions and ascertain any factors of stabilization/destabilization.

Blood Substitutes↗