Biomedical subjects

J Weers

Publications and source records attributed to J Weers.

5 recordsLinked to original sources

PubMed2001

Liquid dose pulmonary instillation of gentamicin PulmoSpheres formulations: tissue distribution and pharmacokinetics in rabbits.

PURPOSE: To assess the pharmacokinetics and biodistribution of gentamicin, delivered as PulmoSpheres formulations in rabbit serum and lung tissue following intratracheal instillation in a perflubron vehicle. METHODS: Rabbits were anesthetized, intubated, and mechanically ventilated with O2 (FiO2 = 0.50). Animals were then given 5 mg/kg gentamicin either intravenously, intramuscularly (TM), or intratracheally (IT) gentamicin PulmoSpheres formulation, instilled in 1.8 ml/kg of liquid perflubron vehicle. Serum and lung lobe sections were collected at multiple time points and assayed for gentamicin content. RESULTS: Serum gentamicin levels peaked at 64.7 microg/ml, 11.2 microg/ml, and 5.0 microg/ml following intravenous, TM, and IT administration, respectively. Absolute bioavailabilitv at 8 h for IM administration was 76.8% and 57.0% when delivered IT. Although peak lung levels of drug were reached within 1 h, total lung gentamicin concentration after IT administration was more than two orders of magnitude greater than that achieved following TM administration (680,540 vs. 4,985 microg min, respectively) with significant levels of the antibiotic remaining in the lung even after 1 week. CONCLUSIONS: High levels of gentamicin in lung tissue can be achieved by instillation of a gentamicin PulmoSpheres formulation in a perflubron vehicle, termed liquid dose installation, without reaching toxic systemic levels allowing for increased local delivery of agents such as gentamicin at the site of the infection.

Administration, Inhalation↗

PubMed1998

Dissolution of multicomponent microbubbles in the bloodstream: 2. Experiment.

The effect of the nature of the filling gas on the persistence of microbubbles in the bloodstream was studied. All the microbubbles were covered with the same shells. Various perfluorocarbons and perfluoropolyethers alone and as mixtures with nitrogen were used as the filling gases. The persistence time of microbubbles in the bloodstream tau increased with the molecular weight of the filling gas, from approximately 2 min for perfluorethane, to > 40 min for perfluorodiglyme, C6F14O3, and then decreased again to 8 min for C6F14O5. An acceptable ultrasound scattering efficacy was exhibited by the filling gases with intermediate molecular weights that possessed both a high saturated vapor pressure and a comparatively low water solubility (Ostwald coefficient). On the basis of the experimental data, it is concluded that the microbubble persistence tau is controlled primarily by the dissolution of microbubbles and not by the removal of the microbubbles by the reticular endothelial system. Although the qualitative experimental trends are in good agreement with the theoretical model developed previously, there are some quantitative differences. Possible reasons for these differences are discussed.

Air↗

PubMed1998

Dissolution of multicomponent microbubbles in the bloodstream: 1. Theory.

The problem of dissolution of a bubble in the bloodstream is examined. The bubble is assumed to be filled with a mixture of a sparingly water-soluble gas (osmotic agent) and air. The dissolution of the bubble has three definite stages. In Stage 1, the bubble quickly swells in air. The swelling ratio depends on the surface tension, blood pressure, level of oxygen metabolism and initial mole fraction of osmotic agent in the bubble. In Stage 2, the osmotic agent slowly diffuses out of the bubble. The squared radius decreases nearly linearly with time, at a rate proportional to the Ostwald coefficient and diffusivity of the osmotic agent. In Stage 3, the partial pressure of the osmotic agent becomes so high that it condenses into a liquid. In order to prolong the lifetime of 5-micron bubbles in the bloodstream from < 1 s (as found with pure air), the osmotic agent must have a low Ostwald coefficient (< or = 10(-4)) and a relatively high saturated vapor pressure at body temperature (> or = 0.3 atm = 3 x 10(4) Pa).

Air↗

PubMed1996

Phospholipids as Emulsion Stabilizers

The equilibrium phase behavior and the macroemulsion type and stability of oil-water-lecithin mixtures was studied. For dioleyl phosphatidylcholine (DOPC) and n-alkanes as the oil component, the phase equilibrium is characterized by an extended inverse micellar region in equilibrium with water (Winsor II). On the other hand, n-C8F18-DOPC-water and soybean oil-DOPC-water mixtures show a three phase equilibrium of almost pure water, almost pure oil, and lamellar phase Lalpha (Winsor III). Equilibrium phases of DOPC systems can be emulsified in each other. Inverse W/O macroemulsions are favored for all the n-alkanes (C6-C14) studied; O/W emulsions are rather unstable. On the other hand, n-perfluorooctane and soybean oil produced very stable O/W emulsions. The phase behavior and emulsion stabilizing properties of an egg yolk phospholipid mixture is similar to those of DOPC. The phase equilibrium of the saturated analogue of DOPC: distearoyl phosphatidylcholine (DSPC) in mixtures with alkanes and water at room temperature is different and characterized by a Winsor III equilibrium of a Lbeta lamellar phase in a gel state, oil and water. Accordingly, the O/W emulsions are strongly favored to inverse systems. The pattern of the phase equilibrium and macroemulsion stability becomes similar to that of DOPC at elevated temperatures. The macroemulsion stability pattern versus the phospholipid packing type is discussed in relation to the recently proposed theory of emulsion stability to coalescence (Kabalnov, A. and Wennerstrom, H., Langmuir 12, 276 (1996)).

Journal Article↗

PubMed1995

Intraocular tolerance of perfluorooctylbromide (perflubron)

PURPOSE: To determine the intraocular tolerance of perfluorooctylbromide (perflubron) in vitrectomized rabbit and pig eyes and evaluated its use as a vitreous substitute in virteoretinal surgery. METHODS: Pars plana vitrectomy was performed on 33 Dutch pigmented rabbits and 11 micro mini pigs. After vitrectomy the eyes were filled with perflubron for 2 hours, 1 week, 2 weeks, 1 month, and up to 6 months. RESULTS: No clinical, electroretinographic, or light and electron microscopic evidence of adverse effects on the retina and lens were observed. Perflubron emulsified and dispersed into small bubbles after 2-3 weeks. The lens showed mild posterior subcapsular cataracts in pig eyes after long-term retention of perflubron. CONCLUSION: These findings indicate that perflubron is safe for intraoperative and for long-term use intravitreally. However, emulsification and the breakdown into small bubbles limits the view of the retina when perflubron is used as a long-term tamponade.

Animals↗