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At least 703 records · Page 39Linked to original sources
PubMed1998

Influence of processing on the stability and release properties of biodegradable microspheres containing thioridazine hydrochloride.

Biodegradable microspheres of poly(DL-lactic-co-glycolic acid) (PLGA) containing thioridazine HCl were produced by four emulsion-solvent evaporation methods including an O/W emulsion method, an O/O emulsion method, a W/O/W multiple emulsion method, and a W/O/O/O multiple emulsion method. Gel permeation chromatography was used to determine the molecular weight of the polymer before and after processing. Resultant microspheres were either incubated in an oven at 40 degrees C, or stored in a desiccated chamber at 20 degrees C. Change in the molecular weight of the polymer was monitored as a function of time. Premature degradation of the polymer was evident in microspheres produced by the O/W conventional solvent evaporation method. Thioridazine HCl catalyzed hydrolysis of PLGA was evident in normalized molecular weight distribution plots of the O/W microspheres. The in vitro release of thioridazine HCl from multiphase microspheres produced by potentiometric dispersion was compared with the release of drug from conventional microspheres prepared from the same polymer. Release of thioridazine HCl from multiphase microspheres of the W/O/O/O type occurred by diffusion during initial stages of drug release.

Biocompatible Materials↗
PubMed2003

Effect of dexamethasone on motor brachial plexus block with bupivacaine and with bupivacaine-loaded microspheres in a sheep model.

BACKGROUND AND OBJECTIVE: It has been suggested that dexamethasone potentiates the sensory block produced by bupivacaine when both drugs are loaded in microspheres. The aim of the study was to evaluate the effect of dexamethasone on the brachial plexus block obtained with plain bupivacaine and bupivacaine-loaded microspheres. METHODS: Dexamethasone alone (Group 5) or added to plain bupivacaine (75 mg) with (Groups 3 and 4) and without pH correction (Group 2) was compared with plain bupivacaine (75 mg; Group 1). The effect of a small dose of dexamethasone (0.42 mg) was then evaluated on the brachial plexus block obtained with bupivacaine (750 mg) as bupivacaine-loaded microspheres (Group 6). Dexamethasone was added either in the suspending medium (Group 7) or incorporated with bupivacaine into microspheres (Group 8). The motor block was evaluated in a plexus brachial sheep model. RESULTS: Dexamethasone alone did not produce any motor block. When added to plain bupivacaine without pH correction, complete motor block could not be obtained. When the pH was corrected, addition of dexamethasone to plain bupivacaine seemed to delay the onset of motor block and did not prolong its duration, and it had no effect on the pharmacokinetics of bupivacaine. With bupivacaine-loaded microspheres, the duration of complete motor block was reduced when a small dose of dexamethasone was added in the suspending medium. However, the duration of motor block was significantly prolonged when dexamethasone was incorporated with bupivacaine into microspheres. CONCLUSIONS: Despite the delayed onset of motor block, the incorporation of dexamethasone in bupivacaine-loaded microspheres dramatically increases the duration of action (700 +/- 485-5160 +/- 2136 min), which could be clinically relevant when such a drug-delivery system will be available.

Anesthetics, Local↗
PubMedDate not supplied

Fluorescent nanometer microspheres as a reporter for sensitive detection of simulants of biological threats using multiplexed suspension arrays.

We succeeded in using 40 nm FRET (fluorescence resonance energy transfer) microspheres conjugated to antibodies as the fluorescent reporters to perform the multiplexing suspension array measurements on two simulants of biological threats, ricin (A chain) and a crude spore preparation of Bacillus globigii (Bg). The microspheres were impregnated with two types of fluorophores in equal number (approximately 140 fluorophores in total per microsphere) and displayed bright PE-like fluorescence via a fluorescence resonance energy transfer mechanism. Activated microspheres (aldehyde groups) were directly coupled to antibodies and used to form sandwich-type immunoassays in a suspension array. For the crude preparations of Bg, the assay sensitivity using antibody-conjugated microspheres is an order of magnitude higher than that using the conventional fluorescent reporter, R-phycoerythrin (PE). Using the microspheres, Bg at the concentration of 5 ng/mL can be easily detected. For ricin, the assay sensitivity was similar to that obtained using PE as the reporter, but washing the reaction mixtures resulted in the fluorescence signals that were 2-3 times higher compared to those using PE. Ricin at a concentration of 1 ng/mL can be readily identified. Importantly, the two simulants do not interfere with each other in the multiplexing experiments. The 40 nm FRET microspheres are a new sensitive alternative as fluorescent reporters for detection in suspension arrays.

Bacillus↗
PubMed2006

In vitro degradation behavior of microspheres based on cross-linked dextran.

The aim of this study was to investigate the in vitro degradation of hydroxyl ethyl methacrylated dextran (dex-HEMA) microspheres. Dextran microspheres were incubated in phosphate buffer pH 7.4 at 37 degrees C, and the dry mass, mechanical strength, and chemical composition of the microspheres were monitored in time. The amount and nature of the formed degradation products were established for microspheres with different cross-link densities by FT-IR (Fourier transformed infrared spectroscopy), NMR, mass spectrometry, SEC analysis, and XPS (X-ray photoelectron microscopy). The dex-HEMA microspheres DS 12 (degree of HEMA substitution; the number of HEMA groups per 100 glucose units) incubated at pH 7.4 and 37 degrees C showed a continuous mass loss, leaving after 6 months a residue of about 10% (w/w) of water-insoluble products. NMR, mass spectrometry, and SEC showed that the water-soluble degradation products consisted of dextran, low molecular weight pHEMA (M(n) approximately 15 kg/mol), and small amounts of unreacted HEMA and HEMA-DMAP (intermediate reaction product of the Baylis-Hillman reaction of HEMA with DMAP (4-dimethyl aminopyridine)). Microscopy revealed that the water-insoluble residue consisted of particles with shape and size similar to that of nondegraded microspheres. However, these particles had lost their mechanical strength as evidenced from micromanipulation experiments. FT-IR and XPS (X-ray photoelectron microscopy) revealed that these particles consisted of pHEMA, of which a small fraction was soluble in methanol (M(n) ranging between 27 and 82 kg/mol). The insoluble material likely consisted of lightly cross-linked pHEMA. In conclusion, in vitro degradation of dex-HEMA microspheres results in the formation of water-soluble degradation products (mainly dextran), leaving a small water-insoluble residue mainly consisting of pHEMA.

Chromatography, Gel↗
PubMedDate not supplied

Renaturation of reduced ribonuclease A with a microsphere-induced refolding system.

We intended to refold reduced ribonuclease A (RNase A) using polymeric microspheres. Polymeric microspheres were allowed to react with dithiothreitol (DTT) to immobilize the disulfide and thiol moieties on their surface. The fully reduced RNase A was added to the dispersion of the modified microspheres. Protein refolding and renaturation were estimated by the change in the number of disulfide bonds of RNase A and the recovery of the enzymatic activity, respectively. Without microspheres, the activity gradually recovered with the increase in the number of disulfide bonds. However, the formation of disulfide bonds of reduced RNase A was accelerated by adding the modified microspheres, and the rate of renaturation was increased depending on the amount of charged DTT and the reaction time of the immobilization. These results indicate that modified microspheres significantly catalyze the recovery of active RNase A from the reduced form. The protein adsorption data demonstrated that the disulfide moieties of the modified microspheres react with the thiol moieties of the reduced RNase A to form a mixed disulfide. The thiol/disulfide exchange reaction can possibly proceed at the microsphere/protein interface, resulting in the formation of a correct three-dimensional structure.

Biochemistry↗
PubMedDate not supplied

In vitro release profiles of eristostatin from biodegradable polymeric microspheres: protein aggregation problem.

Eristostatin, a low molecular weight polypeptide (MW 5725), was encapsulated within two biodegradable poly(lactic acid-glycolic acid) microspheres. In vitro release profiles from the microspheres exhibited fast initial release for up to several days, followed by very slow or no release. The later stage of the slow release was due to protein aggregation within the microspheres. A simple, noninvasive method to detect the protein aggregation within the microspheres has been developed: extraction of radiolabeled protein from the microspheres by a DC electric field into a polyacrylamide gel and subsequent exposure to a gamma-ray sensitive film. Direct application of the degrading microspheres onto the sample loading zone of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) could successfully extract the monomeric and oligomeric proteins into the autoradiogram of a gel slab, while unextractable protein aggregates within the microspheres could be directly visualized in their loading position.

Autoradiography↗
PubMed1997

A new strategy to determine the actual protein content of poly(lactide-co-glycolide) microspheres.

Bovine serum albumin, lysozyme, and trypsin inhibitor were first encapsulated into poly-d,l-lactide-co-glycolide (PLGA) microspheres and then a new strategy was used to quantitate the actual levels of proteins in the microspheres. The proper combination of water-miscible dimethyl sulfoxide and 0.05 N-NaOH containing 0.5% sodium dodecyl sulfate (SDS) made it possible to solubilize both PLGA microspheres and proteins in a single phase. A total protein assay conveniently provided accurate information on the amount of protein encapsulated into the microspheres. In contrast to conventional techniques making use of acetonitrile, dichloromethane, and SDS extraction methods, this new method did not necessitate polymer precipitation, filtration, and protein extraction into other phases. These features were a great advantage in recovering proteins without any loss due to experimental processes. As a consequence, the new method reported in this study provided accurate data for the actual level of protein in PLGA microspheres, regardless of the pattern of protein distribution inside microspheres or the characteristics of microspheres. The experiment relying on the use of a radiolabeled protein also validated the reliability of this new method.

Lactic Acid↗
PubMed2001

Stabilization and controlled release of bovine serum albumin encapsulated in poly(D, L-lactide) and poly(ethylene glycol) microsphere blends.

PURPOSE: The acidic microclimate in poly(D, L-lactide-co-glycolide) 50/50 microspheres has been previously demonstrated by our group as the primary instability source of encapsulated bovine serum albumin (BSA). The objectives of this study were to stabilize the encapsulated model protein, BSA, and to achieve continuous protein release by using a blend of: slowly degrading poly(D, L-lactide) (PLA), to reduce the production of acidic species during BSA release; and pore-forming poly(ethylene glycol) (PEG), to increase diffusion of BSA and polymer degradation products out of the polymer. METHODS: Microspheres were formulated from blends of PLA (Mw 145,000) and PEG (Mw 10,000 or 35,000) by using an anhydrous oil-in-oil emulsion and solvent extraction (O/O) method. The polymer blend composition and phase miscibility were examined by FTIR and DSC, respectively. Microsphere surface morphology, water uptake, and BSA release kinetics were also investigated. The stability of BSA encapsulated in microspheres was examined by losses in protein solubility, SDS-PAGE, IEF, CD, and fluorescence spectroscopy, RESULTS: PEG was successfully incorporated in PLA microspheres and shown to possess partial miscibility with PLA. A protein loading level of 5% (w/w) was attained in PLA/PEG microspheres with a mean diameter of approximately 100 microm. When PEG content was less than 20% in the blend, incomplete release of BSA was observed with the formation of insoluble, and primarily non-covalent aggregates. When 20%-30% PEG was incorporated in the blend formulation, in vitro continuous protein release over 29 days was exhibited. Unreleased BSA in these formulations was water-soluble and structurally intact. CONCLUSIONS: Stabilization and controlled relaease of BSA from PLA/PEG microspheres was achieved due to low acid and high water content in the blend formulation.

Animals↗
PubMed1989

Effect of drug (core) particle size on the dissolution of theophylline from microspheres made from low molecular weight cellulose acetate propionate.

Three particle sizes (450, 120, and 5 microns) of theophylline were encapsulated in low molecular weight cellulose acetate propionate (intrinsic viscosity, 1.08 dl/g) by the solvent evaporation method. The theoretical drug content for all the batches of microspheres was 50% (w/w). Particle size analysis revealed that about 50% of the microspheres containing the large theophylline crystals (average length of 450 microns) were greater than 500 microns in diameter, whereas only about 35% of the microspheres containing the medium drug crystals (average length of 120 microns) were greater than 500 microns in diameter. The drug content of the larger microspheres prepared from the large drug crystals and the medium drug crystals was much greater than the theoretical drug content (50%, w/w); however, the drug content of all the batches of microspheres containing micronized drug was close to 50% (w/w). Release of the drug in simulated intestinal fluid was very rapid from microspheres containing large and medium drug crystals, while release was slower and more predictable from microspheres made from micronized drug.

Cellulose↗
PubMed1989

Protein precoating of polylactide microspheres containing a lipophilic immunopotentiator for enhancement of macrophage phagocytosis and activation.

Biodegradable microspheres containing a lipophilic muramyl dipeptide, MDP-B30, were prepared from a L-lactic acid-glycolic acid copolymer. The effect of precoating the microspheres with water-soluble polymers including proteins on the antitumor activity of mouse peritoneal macrophages (M phi) was investigated. Macrophages activated by phagocytosis of the microspheres exhibited growth inhibitory activity toward Meth-A tumor cells. The activity correlated with the extent of M phi phagocytosis of the microspheres. M phi phagocytosis was greatly augmented by gelatin precoating of the microspheres, resulting in a significant increase of in vitro antitumor activity of M phi by the microspheres. However, potentiation of M phi activity by gelatin precoating was minimal after intraperitoneal injection of the microspheres, but cross-linking of the coated gelatin with glutaraldehyde afforded potentiation of the antitumor activity in vivo.

Adjuvants, Immunologic↗
PubMed1989

Synthesis of gelatin microspheres containing interferon.

Gelatin microspheres with a diameter less than 2 microns were synthesized by means of cross-linking with glutaraldehyde. When the microspheres were subjected to degradation in phosphate-buffered saline solution containing collagenase, the digestion of microspheres was found to decrease with increasing cross-linking. Interferon was incorporated in the microspheres at a high trapping efficiency, and the rate of interferon release from the microspheres was regulated by the extent of cross-linking with glutaraldehyde. Gelatin microspheres incorporating interferon-alpha were readily phagocytosed by macrophages, regardless of the extent of cross-linking, and the phagocytosed microspheres were observed to be degraded gradually in the interior of macrophages, resulting in the slow release of the incorporated interferon in the cells.

Chemistry, Pharmaceutical↗
PubMed1996

Stable formulations of recombinant human growth hormone and interferon-gamma for microencapsulation in biodegradable microspheres.

PURPOSE: The successful development of controlled release formulations for proteins requires that the protein not be denatured during the manufacturing process. The major objective was to develop formulations that stabilize two recombinant human proteins, human growth hormone (rhGH) and interferon-gamma (rhIFN-gamma), at high protein concentrations (> 100 mg/mL) in organic solvents commonly used for microencapsulation, methylene chloride and ethyl acetate. METHODS: Several excipients were screened to obtain the maximum solubility of each protein. These formulations (aqueous, lyophilized, milled, spray dried, or isoelectric precipitate) were then rapidly screened by emulsification in the organic solvent followed by recovery into excess buffer. Additional screening was performed with solid protein that was suspended in the organic solvent and then recovered with excess buffer. The recovery of native protein was determined by native size exclusion chromatography (SEC-HPLC) and circular dichroism (CD). The selected formulations were encapsulated in polylactic-coglycolic acid (PLGA) microspheres by either water-in-oil-in-water (W/O/W) or solid-in-oil-in-water (S/O/W) methods. The initial protein released from the microspheres incubated at physiological conditions was analyzed by SEC-HPLC, CD, and biological assays. RESULTS: The stability of a given formulation in the rapid screening method correlated well with stability during encapsulation in PLGA microspheres. Formulations of rhGH containing Tween 20 or 80 resulted in lower recovery of native protein, while trehalose and mannitol formulations (phosphate buffer, pH 8.0) yielded complete recovery of native rhGH. Other additives such as carboxymethyl cellulose, gelatin, and dextran 70 were not effective stabilizers, and polyethylene glycol provided some stabilization of rhGH. Trehalose/rhGH (1:4 mass ratio) and mannitol/rhGH (1:2 mass ratio) formulations (potassium phosphate buffer, pH 8.0) were lyophilized, reconstituted to 200 and 400 mg/mL rhGH, respectively, and then encapsulated in PLGA microspheres. The protein was released from these microspheres in its native state. Lyophilized formulations of rhGH yielded analogous results indicating the ability of trehalose and mannitol to stabilize the protein. Small solid particles of rhGH generated by spray drying (both air and freeze-drying) formulations containing Tween 20 or PEG were stable in ethyl acetate, but not methylene chloride. Similar results were also obtained with rhIFN-gamma (137 mg/mL in succinate buffer, pH 5.0), where both mannitol and trehalose were observed to stabilize the protein during exposure to the organic solvents resulting in the release of native rhIFN-gamma from PLGA microspheres. CONCLUSIONS: The rapid screening method allowed the development of stable concentrated protein solutions or solid protein formulations that could be successfully encapsulated in PLGA microspheres. The excipients observed to stabilize these proteins function by preferential hydration of the protein, and in the dry state (e.g., trehalose) may stabilize the protein via water substitution yielding a protective coating around the protein surface. Studies of other proteins should provide further insight into this mechanism of protein stabilization during encapsulation.

Chemical Precipitation↗
PubMed1994

Development and evaluation of sustained-release ibuprofen-wax microspheres. II. In vitro dissolution studies.

A modified USP paddle method using minibaskets was used to study the effects of various formulations on in vitro dissolution of ibuprofen microspheres. Formulations containing waxes such as paraffin or ceresine wax without modifiers exhibited very slow dissolution profiles and incomplete release, which did not improve with increased drug loading or the preparation of smaller microspheres. The addition of modifiers such as stearyl alcohol and glyceryl monostearate greatly increased the dissolution rate, with 20% (w/w) near the optimum for predictable dissolution. Higher drug loading and decreased microsphere size increased the dissolution rate from microspheres containing modifier. Optimum formulations contained ceresine wax or microcrystalline wax and stearyl alcohol as a modifier, with a drug content of 17%. An increase in the encapsulation dispersant concentration had little effect on the dissolution profiles. The dissolution data from narrow size fractions of microspheres indicated spherical matrix drug release kinetics; the 50% dissolution time decreased with the square of the microsphere diameter. With appropriate modifiers, wax microsphere formulations of drugs with solubility characteristics similar to those of ibuprofen can offer a starting basis for predictable sustained release dosage forms.

Delayed-Action Preparations↗
PubMed1994

Formation and characterization of cisplatin-loaded poly(benzyl l-glutamate) microspheres for chemoembolization.

Chemoembolization using microspheres of 100- to 200-microns is a useful way to treat primary and secondary hepatic tumors. In a search for a better embolic material, we described in detail the preparation and characterization of a poly(benzyl l-glutamate) (PBLG) microspheres containing cisplatin (CDDP). We determined the optimal experimental conditions to produce spherical free-flowing microspheres that were able to release drug content (44% [w/w] CDDP) in a sustained manner. We found that solvent viscosity played a key role in determining the resulting microsphere characteristics. Microscopic studies showed that increasing the polymer concentration (to 10% [w/v]) and the viscosity of the organic phase produced microspheres with uniform drug distribution. Increasing polymer concentration also markedly improved drug incorporation efficiency. In vitro release studies revealed that the release of CDDP was a function of drug loading; microspheres with a higher amount of entrapped CDDP had a slower release rate. This observation and the fact that CDDP/PBLG microspheres did not show "burst effect" at higher loading is ascribed to the formation of uniformly distributed drug crystal networks within the polymer matrix. The favorable properties of the CDDP/PBLG system warrants its further evaluation on experimental animal models for the treatment of hepatic tumors.

Chemoembolization, Therapeutic↗
PubMed1993

Sustained bronchodilation with isoproterenol poly(glycolide-co-lactide) microspheres.

An animal study was carried out to evaluate the in vivo bronchodilator action of isoproterenol (Iso) from poly(glycolide-co-lactide) (PGL) microspheres. Microspheres with a mean diameter of 4.5 microns and a drug load of 7% were administered intratracheally to Long-Evans rats. The microspheres released about 70% of the incorporated drug in the instillation medium before administration, which provided immediate action, and the remaining 30% was available for sustained release. A total of 120 animals was anesthetized, paralyzed, artificially ventilated, and divided into 15 groups (n = 8): 3 groups each for saline, blank microspheres, free Iso, blank microspheres with free Iso, and microencapsulated Iso. All instillations were made in a volume of 1 ml/kg and the dose of all Iso preparations was 0.1 mg/kg. At 3, 6, or 12 hr after the intratracheal instillation, a serotonin challenge (40 micrograms/rat) was administered intravenously to constrict the airways. Airway function tests were performed at each time interval on one group of animals by a maximal expiratory flow-volume maneuver. The heart rate in animals receiving Iso formulations was similar to that in the saline control group, indicating minimal systemic effect of the dose administered. The systemic serum levels were below 2 ng/ml in all the groups. Animals receiving encapsulated Iso resisted the serotonin challenge for at least 12 hr after intratracheal instillation, indicating that the drug was still present over this period of time. On the other hand, the serotonin-induced airway constriction observed in the animals receiving blank microspheres, free Iso, or free Iso with blank microspheres was similar to that in saline controls at all time points. The results clearly show that only a small fraction of the free dose is required in sustained-release form for a prolonged pharmacological effect, resulting in a 50- to 100-fold reduction in the total dose administered.

Animals↗
PubMed2003

High bioavailabilty of alpha-tocopherol loaded into poly (DL-lactic-co-glycolic acid) microspheres in apolipoprotein B knockout mice.

PURPOSE: To assess the potential clinical value of alpha-tocopherol-loaded poly (DL-lactic-co-glycolic acid) (PLGA) microspheres, we examined the disposition kinetics of alpha-tocopherol after administration of the microspheres to apolipoprotein B (apo B) knockout mice as a model of abetalipoproteinemia. METHODS: PLGA microspheres containing alpha-tocopherol were prepared by a solvent-evaporation method. The concentration of alpha-tocopherol was measured by gas chromatography-mass spectrometry. RESULTS: The mean value of particle size of alpha-tocopherol-loaded PLGA microspheres was 108 microm. The loading and the trapping efficiency of alpha-tocopherol in PLGA microspheres were 20.8% and 86.6%, respectively. When alpha-tocopherol solution (25 mg/kg) was subcutaneously administered to apob (+/+) and apob (+/-) mice, the plasma concentrations of alpha-tocopherol reached a peak at 6 h and decreased to the endogenous level within 4 days in both types of mice. However, the area under the plasma concentration-time curve (AUC) of apob (+/-) mice was significantly smaller than that in the case of apob (+/+) mice. When alpha-tocopherol-loaded PLGA microspheres (100 mg/kg) were subcutaneously administered, the plasma concentrations of alpha-tocopherol increased slowly and remained about 2-fold higher than the endogenous level at 5 to 10 days after administration in both types of mice, and there was no significant difference between the AUC values. CONCLUSIONS: The PLGA microsphere preparation of alpha-tocopherol is expected to be a very useful drug delivery system in vitamin E supplementation therapy for abetalipoproteinemia.

Animals↗
PubMed1989

Enhanced in vivo activity of adriamycin incorporated into controlled release microspheres.

A comparison of the cytotoxic effectiveness of adriamycin incorporated into ion exchange microspheres with conventional chemotherapeutic use of adriamycin was carried out in a rat tumour model. Drug microspheres were targeted to the tumours by embolisation into the arterial supply of the hind limb bearing the tumour. Microspheres were found to embolise in tumour tissue at concentrations of up to 39 times that of the surrounding normal tissue. As a result, adriamycin microsphere therapy was found to retard significantly (P less than 0.01) tumour growth rates compared to growth rates associated with similar doses of adriamycin delivered as free drug rather than bound to controlled release microspheres. Equivalent sham microsphere treatments showed no significant difference in tumour growth rates compared with the control group. Adriamycin loaded on to ion exchange microspheres holds strong potential for treatment of human malignancy.

Adenocarcinoma↗
PubMed1975

Measurement of intrarenal blood-flow distribution in the rabbit using radioactive microspheres.

1. Total renal blood flow and its distribution within the renal cortex of the conscious rabbit were studied with radioactive microspheres of 15 and 25 mum diameter. 2. The reliability of the microsphere technique was influenced by microsphere diameter and number (dose). The optimum microsphere diameter for determination of flow distribution in the rabbit kidney was 15 mum and dose 100-150 000 spheres. 3. Spheres of 15 mum nominal diameter were randomly distributed within the renal cortex of adult rabbits. The larger spheres in batches nominally 15 mum in diameter in young rabbits and 25 mum diameter in adult rabbits were preferentially distributed to the superficial cortex. 4. In adult rabbits 15 mum diameter spheres lodged in glomerular capillaries. Larger spheres occasionally lodged in interlobular arteries causing intrarenal haemorrhage. 5. Microspheres of 15 mum caused a decrease in renal clearance of creatinine and of p-amino-hippurate when the total injection dose was about 200 000 spheres. These effects were greater when the injection dose was increased to 500 000 spheres. 6. The reduction in total renal blood flow observed with large doses of spheres largely reflected decreased outer cortical flow, as measured by a second injection of spheres, and confirmed by a decrease in p-aminohippurate extraction. 7. The reproducibility of multiple injection studies was limited by these intrarenal effects of microspheres. 8. Total renal blood flow measured in six rabbits in acute experiments by the microsphere technique was 107 plus or minus 12 (mean plus or minus SD) ml/min and by p-amino-hippurate clearance was 100 plus or minus 10 ml/min. 9. Total renal blood flow in twelve conscious, chronically instrumented rabbits was 125 plus or minus 11 ml/min, of which 92 plus or minus 6 ml/min was distributed to the superficial cortex and 33 plus or minus 4 ml/min to the deep cortex.

Animals↗