Bovine Serum Albumin Microspheres Research Articles

Development of specific organ-targeting drug delivery system I: Physico-pharmaceutical characteristics of thermally denatured albumin microspheres containing cytarabine

In attempt to develop a drug delivery system using serum albumin microspheres, bovine serum albumin microspheres containing antitumor agent, cytarabine, were prepared. The shape, surface characteristics, size distribution, behavior ofin vitro distribution, drug release behavior, and degradation of albumin microspheres in animal liver tissue homogenate and proteolytic enzyme were investigated. The shape of albumin microspheres was spherical and the surface was smooth and compact. The size distribution of the albumin microspheres was affected by dispersion forces during emulsification and albumin concentration. Distribution of albumin microspheres after intravenous administration in rabbit was achieved immediately.In vitro, albumin microsphere matrix was so hard that it retained most of cytarabine except initial burst during the first 10 minutes, and the level of drug release during the initial burst was affected by heating temperature, drug/albumin concentration ratio and size distribution. After drug release test, the morphology of albumin microspheres was not changed. Albumin microsphere matrix was degraded by the rabbit liver tissue homogenate and proteolytic enzyme. The degree of degradation was affected by heating temperature.

Labeling Suspended Aerosol Particles with Short-lived Radionuclides for Determination of Particle Deposition

Radiotracer techniques were developed to examine parameters that characterize pressurized aerosols designed to deliver insoluble particles suspended in the aerosol formulation. Microaggregated bovine serum albumin microspheres that were to be suspended were labeled with iodine-131 (t1/2 = 8 d). This iodination procedure (>80% effective) is also applicable to iodine-123, which possesses superior characteristics for external imaging and further in vivo studies. This report shows that for pressurized aerosols containing suspended particles, each metered dose is approximately equal (not including the priming doses and the emptying doses). Increase in the delivery of the albumin particles out of the canister was best achieved by pretreating the valve assembly with a solution of 2% (w/v) bovine serum albumin in phosphate buffer. Use of a cascade impactor delineated the particle size distribution of the micropheres, with the majority of particles ranging in size from 2 to 8 μu. The data disclosed here indicate that the techniques developed with short-lived radionuclides can be used to (a) quantitate each metered dose, (b) characterize the particle size distribution profile of the aerosol contents, and (c) determine the extent of deposition of the particles in the aerosol canister and all of its components.

Characterization of Albumin Microspheres by Sedimentation Field‐Flow Fractionation

Sedimentation field‐flow fractionation (FFF) is a new technique that separates and characterizes submicron particles. In the present work, two independent sedimentation FFF methods are presented to characterize bovine serum albumin microspheres in terms of particle size, polydispersity, and diffusion coefficient. Particle diameters and polydispersities determined by the two sedimentation FFF methods were in excellent agreement with each other and in good agreement with values calculated from transmission electron microscopy (TEM) measurements. The diameters calculated from the two FFF methods and TEM were 0.349,0.346, and 0.354 μm, respectively.

Drug-carrier property of albumin microspheres in chemotherapy. II. Preparation and tissue distribution in mice of microsphere-entrapped 5-fluorouracil.

Bovine serum albumin microspheres contatining 5-fluorouracil-6-3H were prepared by heating at 180° (or 150°, 100°) of 25% albumin solution in cottonseed oil emulsion. The shape of this microsphere was invariably spherical, and the average diameter was 0.66μ. After intravenous injection in mice, 5-fluorouracil-6-3H entrapped in albumin microspheres localized mainly in the liver, and the disappearance rate of radioactivity in microspheres from the tissue was very slow in comparison with that of free drugs. The microsphere might be delivered into reticuloendothelial system in the liver because ofits phagocytic activity, as well as the distribution following injection of albumin macroaggregates. Such preferential localization and sustained release of entrapped drugs suggested that albumin microspheres are useful as drug-carrier in chemotherapy.

Specific Removal of Bovine Serum Albumin (BSA) Antibodies in Vivo by Extracorporeal Circulation over BSA Immobilized on Nylon Microcapsules

Studies were undertaken to determine whether BSA, once immobilized on activated nylon microspheres, would be capable of specifically removing circulating BSA antibody in vitro and in vivo in an extracorporeal circulation system in dogs. Nylon microspheres were prepared and, after gentle hydrolysis and glutaraldehyde treatment, demonstrated a retention of up to 34.5 mg of BSA. In vitro studies showed that BSA immobilized on microspheres removed a significant percentage of BSA-binding activity. For in vivo studies, an extracorporeal circulation system was established and mongrel dogs were then injected with anti-BSA and anti-HSA antibodies. After an equilibration period, BSA microspheres were introduced into the extracorporeal circulation system. After the insertion of BSA microcapsules, serum exhibited a sharp reduction in BSA binding over the next 15 min, with a more gradual diminution over the ensuing 60 to 90 min. There was no significant reduction in anti-HSA binding over the same time frame. This effect could not be attributed to release of BSA from the microspheres since no 125I-BSA was detected in the serum or organs of the dogs at the conclusion of the experiments. After extracorporeal circulation over nylon microspheres, there were only minimal changes in the host's hematocrit or leukocyte counts and no significant thrombotic material or cellular debris was recoverable on the capsules. These data suggest that antigen immobilized on nylon microspheres may specifically withdraw circulating antibodies in vivo with minimal release of its antigenic material and little alteration in the host's hematologic status.