Search PubMed⌕ Search

Biomedical subjects

P Edman

Publications and source records attributed to P Edman.

At least 19 recordsLinked to original sources
PubMed1992

Effect of particle size on ocular permeability of prednisolone acetate in rabbits.

The ocular permeability of two sieved fractions of prednisolone acetate with a mean particle size of less than 5 microns and 5-10 microns was studied in rabbits. The results show that there was not significant difference between the corneal uptake of the two fractions of prednisolone acetate. Prednisolone acetate was rapidly taken up by the cornea where it is hydrolyzed rapidly to prednisolone. Only prednisolone was detected in the aqueous humor showing that prednisolone acetate is completely hydrolyzed in the cornea. Both fractions produced similar concentrations of prednisolone in the aqueous humor. For prednisolone acetate, the permeability rate rather than the dissolution rate seems to be the rate-limiting step for corneal transport.

Administration, Topical↗
PubMed1990

Precorneal residence time in humans of sodium hyaluronate as measured by gamma scintigraphy.

The aim of the present study was to quantify in man the distribution and clearance of two aqueous sodium hyaluronate (SH) solutions of 0.125% and 0.250% after the administration of 25 microliters onto the cornea. Isotonic phosphate buffer (PB) was used as a reference instillation. No systemic or local medication was given to the seven 18- to 30-year-old, healthy male volunteers. A detailed evaluation of the anterior segment of the eye, as well as a Schirmer test and a break-up time measurement, yielded results within the normal range. The clearance of 0.125% and 0.250% SH solutions radiolabelled with sodium pertechnetate Tc-99m was measured by gamma scintigraphy and compared with that of a PB solution tagged with the same radiolabel. There was no statistically significant difference between the quantities of 0.125% SH and PB solutions remaining in the precorneal space at 20 min (paired t-test, P = 0.78, n = 7). However, in comparing the 0.250% SH with the PB solution, we observed a statistically significant difference (P = 0.01, n = 7) in the amount remaining in the precorneal space after the same interval. Actually, 53% of the radiolabelled 0.250% SH solution remained on the cornea as compared with 30% for the 0.125% SH solution and 18.3% for the PB solution. These results suggest that an SH solution of 0.250% might have a prolonged residence time on the precorneal surface, and that SH could therefore be used as an additive in various drug-release systems for the eye.

Administration, Topical↗
PubMed1989

Sodium hyaluronate as an ophthalmic vehicle: some factors governing its effect on the ocular absorption of pilocarpine.

Sodium hyaluronate, as an additive to aqueous ophthalmic formulations, has been claimed to increase the ocular contact time and, thereby, the drug bioavailability. In the present study, the effect of sodium hyaluronate on corneal residence time and drug absorption in rabbits was investigated. Addition of sodium hyaluronate (0.125%) to a 3H-pilocarpine HCl solution resulted in increased retention of radioactivity in tear fluid and a 2-fold increase in drug concentration in the cornea and aqueous humor. Further, the effects of concentration and molecular weight of sodium hyaluronate on the miosis induced by pilocarpine in rabbits were studied. A significant increase of miotic response was seen at concentrations just less than 0.1% sodium hyaluronate. Pilocarpine solutions prepared from high mol.wt. sodium hyaluronate exhibited a greater miotic response than those prepared from lower mol.wt. samples. This might indicate that other physicochemical properties of sodium hyaluronate influence drug bioavailability.

Administration, Topical↗
PubMed1988

Biodegradable microspheres. VII: Alterations in mouse liver morphology after intravenous administration of polyacryl starch microparticles with different biodegradability.

Semisynthetic polyacryl starch microparticles are being investigated as drug carriers. In the present paper the possible adverse effects, reflected as morphological alterations, of iv administration of polyacryl starch microparticles were studied in mice. The spleen, lungs, and kidneys displayed a normal morphology after microparticle administration, while dose-dependent reversible alterations of the liver morphology were observed. The alterations initially consisted of vacuolization of the hepatocytes along the sinusoids, followed by unicellular hepatocyte necrosis and formation of granulomas. Later, an increased number of mitotic cells reflected tissue generation and, after two weeks, the tissue morphology was essentially normalized, with the exception of an increased number of binucleated hepatocytes. After repeated administration of the particles in low doses, the same types of alterations were observed but the kinetics of tissue repair was slower. Possible mechanisms inducing these alterations are discussed and comparisons are made with the effects of synthetic polyacrylamide microparticles.

Animals↗
PubMed1988

Coprecipitation of enzymes with water soluble starch--an alternative to freeze-drying.

Krill proteases were prepared in solid form from a partially purified extract by coprecipitation of the enzymes with water-soluble starch in an organic solvent at 22 degrees C. The precipitation did not affect the activity of the enzymes. The recovery of proteolytic activity was 100%. The thermostability of the krill proteases increased when incorporated in the starch precipitate. No reduction in enzymatic activity could be seen after storage at +50 degrees C for 99 days. After milling the coprecipitate could be dispensed. The enzyme preparation consisted of irregular needle-shaped particles. This simple precipitation technique offers an alternative to freeze-drying or spray-drying.

Animals↗
PubMed1987

Biodegradable microspheres. V: Stimulation of macrophages with microparticles made of various polysaccharides.

The interaction between four different microparticulate drug carriers and macrophages was investigated in vitro. The microparticles, consisting of crosslinked starch (1,4-alpha-D-glucan with 1,6-alpha-branches), dextran (1,6-alpha-D-glucan with 1,3-alpha-branches), lichenan (1,3-beta-D-glucan), or mannan (1,6-alpha-D-mannan with 1,2-alpha- and 1,3-alpha-branches), were investigated for their macrophage stimulatory properties. Macrophage stimulation was assayed by the uptake of [14C]glucosamine and stimulatory indices were calculated. Microparticles made of crosslinked lichenan were most stimulatory, followed by the biologically inert mannan and dextran microparticles. Biodegradable starch microparticles were less stimulatory to the macrophages than the other microparticles. All microparticles were phagocytosed to the same extent and stimulated the macrophages to release oxygen radicals. Lichenan, mannan, and dextran microparticles induced morphological changes in the macrophages when given in nontoxic doses. No morphological changes were observed when the macrophages were exposed to starch microparticles or soluble polysaccharides.

Animals↗
PubMed1987

Macrophage stimulation with some structurally related polysaccharides.

The macrophage-stimulating properties of some structurally related polysaccharides were studied in vitro. When the polysaccharides were presented to the macrophages in a sterically fixed form, i.e. as microparticles, they induced the release of interleukin 1 (IL-1) from the macrophages. Microparticulate 1.3-beta-glucan (curdlan) induced nonspecific macrophage mediated tumour cell killing while 1.4-alpha-glucan (starch), 1.6-alpha-glucan (dextran), and 1.6-alpha-mannan were without effect. The corresponding soluble polysaccharides did not stimulate the macrophages. Kinetic studies showed that although IL-1 was released immediately after stimulation, the macrophages needed a time lag of several days to develop tumour cytotoxicity. The development of cytotoxicity paralleled binding of tumour cells to the macrophages. Resident and inflammatory peritoneal macrophages showed differences in their responses to the polysaccharides. Stationary, resident peritoneal macrophages stimulated by macroparticles secreted high levels of IL-1 but expressed a low cytotoxic activity, while newly recruited inflammatory macrophages released lower levels of IL-1 but readily killed the tumour cells. The influence of cyclo-oxygenase products on the IL-1 release and macrophage cytotoxicity was also investigated. When cyclo-oxygenase was blocked with indomethacin, a significantly higher release of IL-1, and then an increased cytotoxicity, were obtained with 1.3-beta-glucan stimulated macrophages. The results suggest that microparticulate polysaccharides may be useful for studies on the induction of macrophage differentiation and also for studies on nonspecific cellular immune responses in vitro and in vivo.

Animals↗
PubMed1987

Influence of sodium hyaluronate on the meiotic effect of pilocarpine in rabbits.

Sodium hyaluronate is a potential vehicle for drugs given topically to the eye. In the present study, the effect of sodium hyaluronate on the miosis induced by pilocarpine in rabbits was investigated. Addition of 0.2 and 0.75% sodium hyaluronate to 1% pilocarpine hydrochloride in buffer resulted in an increased effect measured as area under the miosis-time curve (AUC) and duration of miosis. A comparison between a commercially available 1% pilocarpine preparation and the preparations containing sodium hyaluronate showed that sodium hyaluronate improves the effect parameters. No adverse effects with sodium hyaluronate were observed. Possible mechanisms inducing these improvements are discussed.

Animals↗
PubMed1986

Acrylic microspheres in vivo. X. Elimination of circulating cells by active targeting using specific monoclonal antibodies bound to microparticles.

The elimination from the blood of 51Cr-labelled mouse erythrocytes modified with trinitrophenyl (TNP) groups was followed in mice. After 24 hours, when a stable concentration of the labelled erythrocytes has been attained, monoclonal anti-TNP-antibodies were given intravenously, either in free, soluble form, or bound to microparticles containing immobilized protein A. The anti-TNP-antibodies induced a rapid elimination of the TNP- and 51Cr-labelled erythrocytes. Over the 8-hours time period studied, the elimination rate was significantly faster when the antibodies were administered bound to the particles. After the elimination of the target cells, the radioactivity was found in the liver, spleen and bone marrow. These results and relevant control experiments indicate that a solid carrier 1. can be directed to a specific target cell with a specific antibody and 2. can induce a rapid elimination of the target cell from the circulation.

Acrylic Resins↗
PubMed1986

Studies on microbial contamination of reused disposable plastic insulin syringes.

The microbial contamination of reused disposable insulin syringes and bottles was studied. Fourteen patients, aged 16-64 years, took part in the study. 50 syringes and 52 bottles were examined for sterility at different stages of use. Twelve (24%) syringes and 4 (8%) bottles were found to be contaminated by micro-organisms, although only in low numbers. The micro-organisms recovered belonged to the normal skin flora of man.

Adolescent↗
PubMed1985

Biodegradable microspheres II: Immune response to a heterologous and an autologous protein entrapped in polyacryl starch microparticles.

Human serum albumin (HSA) and mouse serum albumin were entrapped in biodegradable microparticles of polyacrylstarch. When HSA entrapped in microparticles was injected i.v. in Balb/c mice a dose-dependent immune response was elicited. No detectable response was obtained when mouse serum albumin entrapped in microparticles was given to the mice. Neither was any response detected when free HSA or free HSA in combination with empty microparticles were injected, as measured by indirect plaque-forming cells in the spleen and serum antibody titers. The immune response to entrapped HSA had a long duration and was mainly T-cell-dependent as athymic nude mice (Nu/Nu) only generated a weak immune response upon injection of the particle entrapped antigen.

Animals↗
PubMed1984

Ultrastructural alterations in macrophages after phagocytosis of acrylic microspheres.

The effect of microparticles on the survival of cultured mouse peritoneal macrophages was investigated using doses of 0.01-0.1 mg of lyophilized particles/ml of medium and 5 X 10(5) cells, corresponding to approximately 4000-40,000 particles per cell. The lowest dose did not significantly change the survival time as compared with the controls, while approximately 75% of the cells were lost during the first 48 h on exposure to the highest dose. High doses of particles induce cellular damage. The morphology and stability of the lysosomal apparatus was followed with electron microscopy, acid phosphatase cytochemistry, and acridine orange uptake. Alteration of the lysosomal vacuome was characterized by a greatly enhanced rate of autophagocytosis, the formation of huge secondary lysosomes containing microparticles, and labilization of the vacuome with loss of acidity and a tendency to leak acid phosphatase into the cell sap.

Acid Phosphatase↗
PubMed1984

Characterization of polyacryl starch microparticles as carriers for proteins and drugs.

Biodegradable microparticles of cross-linked starch (maltodextrin) have been designed as carriers of proteins and low molecular weight drugs in vivo. Methods are presented for the synthesis of acryloyl starch and its polymerization to microparticles. Macromolecules were immobilized in the microparticles in high yields, i.e., up to 40% of the dry weight consisted of the immobilized protein. The optimal conditions of immobilization were investigated by varying the concentration of starch (D), the concentration of acryloyl groups (T), and the amount of additional cross-linking agent (C). Exclusion of the cross-linking agent gave maximal immobilization of the macromolecules. Enzyme kinetics, release profiles, surface localization, and heat stability of the immobilized macromolecules are also presented. Micro-particles based on starch with small amounts of acryloyl groups were completely degraded after incubation with amyloglucosidase. The degradation of microparticles in serum and in the target organelle, the lysosome, was investigated in vitro. The polyacrylic starch microspheres (mean diameter, 0.5 micron) constitute an attractive alternative to other drug and enzyme carriers.

Biotransformation↗
PubMed1984

Biodegradable microspheres. I. Duration of action of dextranase entrapped in polyacrylstarch microparticles in vivo.

Dextranase was entrapped in polyacryl starch microspheres of different compositions by emulsion polymerization. After i.v. injection in mice and rats, the particles were removed from the blood circulation by macrophages of the reticuloendothelial system. In these cells, the particles are accumulated in the lysosomes. The degradation of different 14C-labeled microparticles and their entrapped dextranase was followed in an isolated lysosomal fraction in vitro and in liver and spleen after i.v. injection in mice. The duration of entrapped dextranase in vivo was followed directly, i.e., by an enzyme assay, and indirectly by following the decrease of a stored material, [3H]dextran in the liver. The degradation of the entrapped enzyme was dependent on the composition of the particle matrix. More cross-linked spheres could better protect the entrapped enzyme in vitro and in vivo. The half-life of free dextranase in the lysosomal fraction was estimated to be about 4 hr, whereas the duration of entrapped dextranase in the liver was at least 48 hr, as measured with [3H]dextran. Finally, the effect of entrapped and free dextranase on an artificially induced storage disease was studied. The stored [3H]dextran was eliminated completely when dextranase was used in microparticles, whereas free dextranase had no effect in vivo.

Animals↗
PubMed1983

Acrylic microspheres in vivo VIII: distribution and elimination of polyacryldextran particles in mice.

The disposition of different 14C-labeled, biodegradable polyacryldextran microparticles after intravenous injection has been studied in the mouse. The particles were rapidly cleared from the circulatory system by the reticuloendothelial system. They were predominantly (60-80%) found in the liver and spleen and to some extent in the bone marrow. Large particle aggregates were found in the lungs 6 hr postinjection. After redistribution, the particles were eliminated from the organs with an apparent t 1/2 of 12-30 weeks, depending on the composition of the particles. Highly cross-linked particles with 2% acrylic groups (DTC = 11-2-75) had a half-life similar to that of polyacrylamide particles (TC = 8-25). The metabolism rate was also correlated with the degradation in vitro with isolated rat lysosomes. After intravenous injection of small 14C-labeled polyacrylamide particles (0.2-0.5 micron), significant amounts of radioactivity were detected in the bile and gallbladder.

Acrylic Resins↗