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Biomedical subjects

W G Love

Publications and source records attributed to W G Love.

13 recordsLinked to original sources
PubMed1995

Methods for assessing splenic macrophage depletion by liposome encapsulated clodronate.

Small unilamellar vesicles containing clodronate (SUVc) injected intravenously will deplete splenic macrophages and the degree of histological depletion can be assessed by determining the clearance and uptake of monoclonal antibody coated erythrocytes. Splenic Fc dependent clearance, assessed in decomplemented animals, provides a more sensitive index of the effects of large multilamellar liposome encapsulated clodronate (MLVc) and SUVc than does the clearance of complement coated erythrocytes on macrophage depletion in the spleen. MLVc were more efficient than SUVc in inducing a reduction in the number of red pulp macrophages within the spleen. Receptor specific red cell uptake in the spleen could be used as an alternative to histology when assessing splenic macrophage depletion. Encapsulation of clodronate is crucial to its depleting effect since the free drug in saline does not change splenic macrophage number or function.

Animals↗
PubMed1995

The effect of free and liposome-encapsulated clodronate on the hepatic mononuclear phagocyte system in the rat.

Clodronate, encapsulated within small unilamellar vesicles (SUVc) will deplete hepatic macrophages after intravenous injection. Functional studies, using probes to evaluate hepatic Fc and C3b uptake, showed a close correlation between the inhibition of receptor-mediated uptake and the depletion of hepatic macrophages. Twenty milligrams of clodronate encapsulated within SUVc produced > or = 90% inhibition of uptake and clearance of Fc- and C3b-coated erythrocytes and a comparable reduction of hepatic macrophage numbers. Inhibition of macrophage receptor-mediated uptake of these erythrocytes was closely related to the reduction in macrophage numbers. Repopulation of macrophages within the liver took place over 2 weeks. At 1 week after depletion, although repopulation was taking place, receptor-mediated function remained suppressed. In a preliminary experiment, treatment of rats with adjuvant arthritis with 20 mg clodronate encapsulated in SUV suppressed the inflammation and reversed the course of the disease, while treatment with 20 mg free clodronate in saline or 20 mg clodronate in multilamellar vesicles (MLVc) did not.

Animals↗
PubMed1994

Interaction between zinc(II)-phthalocyanine-containing liposomes and human low density lipoprotein.

The interaction of human low density lipoprotein (LDL) and small unilamellar liposomes containing the photosensitiser zinc(II)-phthalocyanine (Zn-Pc) was studied in vitro to determine if Zn-Pc could be directly incorporated into the lipoprotein in the absence of other serum components. Incubation of LDL with increasing concentrations of liposomes resulted in a progressive increase in the net negative charge of LDL as determined by agarose gel electrophoresis and both Zn-Pc and liposomal phospholipid were incorporated into the modified LDL particles. Gel chromatography experiments indicated an increase in the molecular mass of modified LDL and immunoaffinity chromatography provided evidence that apoprotein B epitopes on modified LDL were unable to bind to antibody. The study indicated that the liposomal components could be selectively incorporated into LDL by a process that did not appear to involve either aggregation or fusion of particles.

Carbon Radioisotopes↗
PubMed1994

In vitro interaction of zinc(II)-phthalocyanine-containing liposomes and plasma lipoproteins.

We have studied the interaction of small unilamellar liposomes containing zinc(II)-phthalocyanine (Zn-Pc) with human plasma lipoproteins. High-, low- and very low-density lipoproteins (HDL, LDL and VLDL), were purified from plasma and combined in amounts reflecting their natural abundance in plasma. After short periods of incubation at 37 degrees C, the bulk of Zn-Pc was incorporated into HDL and LDL; very little 14C-labelled palmitoyl oleoyl phosphocholine, the most abundant phospholipid in the formulation, was associated with lipoproteins. When liposomes were incubated in pooled plasma, 73%-85% of Zn-Pc and 27%-34% of radiolabelled phospholipid were recovered with HDL and LDL, indicating a possible role for plasma lipid transfer proteins in the incorporation of phospholipid into lipoproteins. Some Zn-Pc was also found in association with VLDL. The buoyant density of Zn-Pc liposomes increased in a dose-dependent fashion when the particles were incubated with plasma, and it is suggested that this was due, at least in part, to opsonization of liposomes by plasma proteins.

Autoradiography↗
PubMed1992

Efficient clodronate entrapment within multilamellar and unilamellar liposomes.

Clodronate (dichloromethylene bisphosphonate) encapsulated within liposomes and administered intravenously eliminates resident macrophages within the liver and spleen. Macrophage depletion in the rat requires 20 mg of the encapsulated drug, and so far this has only been achieved using large multilamellar vesicles (MLV). Recent studies have shown that small unilamellar vesicles (SUV) when injected intravenously accumulate at inflamed joint sites in both animal models of arthritis and patients with rheumatoid arthritis; multilamellar vesicles were not able to do so. If phagocytic cells, such as macrophages, are responsible for SUV sequestration, then SUV containing clodronate may be targeted to the inflamed joint and may eliminate the macrophage population leading to reduction in the state of inflammation. We have adapted an existing technique to radiolabel clodronate with 99mTechnetium to use as a tracer to determine its encapsulation within liposomes, a technique that has advantages over other current methods. We have achieved a high-encapsulation efficiency of the drug within MLV and produced SUV containing sufficient clodronate to deplete macrophages in rats in a small enough volume to administer it intravenously as a single dose.

Chromatography, High Pressure Liquid↗
PubMed1992

Accumulation of polyvinylpyrrolidone within the inflamed paws of adjuvant-induced arthritic rats.

125I-Labelled polyvinylpyrrolidone ([125I]PVP) of a range of molecular weights (mol. wt 10, 40 and 360 kDa) was injected i.v. into adjuvant-induced arthritic and normal rats and the blood clearance and tissue distribution of the polymers determined. The half-life of PVP in the circulation increased with increasing mol. wt; 10, 40 and 360 kDa polymers had mean terminal half-lives of 2.2, 6.9 and 16.4 h, respectively. Tissue uptake was also found to be mol. wt dependent, the largest PVP molecule accumulating to a greater extent in the spleen, liver, lungs and paws in both normal and arthritic rats (P less than 0.01) than the two lower mol. wt polymers. Accumulation of the polymer in inflamed paws (g tissue)-1 greatly exceeded that of normal paws (P less than 0.01). This difference was particularly noticeable with 360 kDa PVP, where arthritic paws amassed 7 times more PVP than normal paws.

Animals↗
PubMed1990

Specific accumulation of cholesterol-rich liposomes in the inflammatory tissue of rats with adjuvant arthritis.

High performance liquid chromatography has shown that after intravenous injection cholesterol-poor liposomes (100 nm) are unstable and their phospholipid is redistributed. Under identical conditions cholesterol-rich liposomes remain structurally intact within the circulation. When injected intravenously cholesterol-rich liposomes accumulate within the inflamed paws of rats with adjuvant induced arthritis to the same extent as cholesterol-poor liposomes. Uptake in inflamed tissue of three cholesterol-rich liposome preparations was always significantly greater than the uptake noted in normal tissue. The degree of accumulation in inflamed tissue was found to depend on the size of the liposome, with the greatest uptake, 7% of the injected dose, achieved by the smallest vesicle (100 nm). These results indicate that intact liposomes accumulate at inflamed joint tissue sites. Therefore the passive targeting of anti-inflammatory drugs encapsulated within these liposomes could be contemplated.

Animals↗
PubMed1989

Specific accumulation of technetium-99m radiolabelled, negative liposomes in the inflamed paws of rats with adjuvant induced arthritis: effect of liposome size.

Technetium-99m labelled, negatively charged liposomes accumulate in the inflamed tissue of rats with adjuvant induced arthritis. Up to 10 times more liposome accumulation was seen in inflamed paws than in paws of control rats, and this represented 5.3% of the injected liposome dose. The accumulation of liposomes in inflamed tissue was directly related to the liposome size, the maximal accumulation occurring with liposomes less than 100 nm in diameter.

Animals↗
PubMedDate not supplied

Effect of liposome surface charge on the stability of technetium (99mTc) radiolabelled liposomes.

Using liposomes radiolabelled by the 99mTechnetium-stannous chloride technique we have investigated the effect of surface charge on the stability of the isotope in vitro and in vivo. Dialysis of 99mTc-labelled positive, negative and neutral liposomes, which had been incubated in either saline or normal rat serum showed no significant loss of the isotope from the liposome surface with only 2 per cent of the isotope dialysed. A comparison of gel chromatography with dialysis confirmed that most of the isotope remained attached to the liposome surface, but it did reveal greater loss of the isotope, between 15 and 23 per cent. The liposome clearance rates obtained from 125I-egg phosphatidylcholine (EPC) and 99mTc dual-labelled positive or neutral liposomes were significantly different. The 99mTc marker was cleared five times faster from the positive liposomes and twice as fast from the neutral liposomes as the 125I-EPC integral membrane marker. The 99mTc attached to liposomes with a negative surface charge was stable in vivo and had the same clearance rate from the circulation as the 125I-EPC marker. These results indicate that the commonly used in vitro techniques for assessing liposome radiolabel stability are unsuitable for predicting the stability of the 99mTc in vivo.

Animals↗
PubMedDate not supplied

High performance liquid chromatographic analysis of liposome stability.

Two techniques have been studied for their suitability for the analysis of the stability of liposomes: (1) High Performance Gel Permeation Liquid Chromatography (HPGPLC), a TSK G5000PW Ultrogel column; (2) Gel Permeation Chromatography (GPC), a Sepharose 4B column. The stability of dual radio-labelled, cholesterol-poor and cholesterol-rich, negatively charged liposomes in vitro (in saline and in serum), and in vivo, have been investigated using these two techniques. The HPGPLC TSK G5000PW column proved to be the superior technique for the analysis of liposome stability with the advantages of rapid run times, increased sample recovery, and smaller sample volumes were required. The results obtained confirm that inclusion of a high ratio of cholesterol into the liposome structure prevents phospholipid loss when exposed to serum, and that the cholesterol-poor liposome structure is dramatically altered under the same conditions. In conclusion, the TSK G5000PW column is ideal for monitoring movement of phospholipid between liposomes and serum proteins and for detecting changes in liposome size.

Animals↗