Interactions of liposomes with the reticuloendothelial system effects of reticuloendothelial blockade on the clearance of large unilamellar vesicles

Kao, Yin J.; Juliano, Rudolph L.

doi:10.1016/0304-4165(81)90259-2

Cited by 133 publications

(43 citation statements)

References 15 publications

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“…The results discussed here probably explain why early attempts to show the opsonic effect of serum on phagocytosis of liposomes by Kupffer cells in vivo [21,22] and in vitro [18] were not successful. These investigators used cholesterol-rich liposomes (----50 mol°70 cholesterol content) and sometimes they used phospholipids other than phosphatidylcholine [19].…”

Section: Discussionmentioning

confidence: 82%

Tissue specific opsonins for phagocytic cells and their different affinity for cholesterol‐rich liposomes

1988

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In accordance with the finding of our in vivo experiments reported earlier [(1983) Biochim. Biophys. Acta 761,142-157; (1986) Biochim. Biophys. Acta 888, 184-190], the results of in vitro experiments show that Kupffer cells avidly take up cholesterol-poor but not cholesterol-rich liposomes, whereas splenic phagocytic cells take up preferentially cholesterolrich rather than cholesterol-poor liposomes in the presence of serum. Evidence presented here suggests that serum contains opsonins specific for hepatic and splenic phagocytic cells and these opsonins have different affinities for cholesterolrich and cholesterol-poor liposomes.

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Section: Discussionmentioning

confidence: 82%

Tissue specific opsonins for phagocytic cells and their different affinity for cholesterol‐rich liposomes

1988

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“…The optimal size of monocyte-targeted liposomes is around 200 nm, for maximizing both efficacy and safety. Large particles (>500 nm) accumulate in the lungs causing thrombosis (52), and particles smaller than 80 nm are, on the other hand, prone to be transported to non-phagocytic cells escaping the MPS (40,41,51,53,54). It should also be noted that vesicles under ∼250 nm can be readily filter sterilized.…”

Section: Discussionmentioning

confidence: 99%

Liposomal Simvastatin Attenuates Neointimal Hyperplasia in Rats

Afergan

David

Epstein

et al. 2010

AAPS J

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Abstract. Monocytes, macrophages, and inflammation play a key role in the process of neointimal proliferation and restenosis. The present study evaluated whether systemic and transient depletion of monocytes could be obtained by a single intravenous (IV) injection of simvastatin liposomes, for the inhibition of neointima formation. Balloon-injured carotid artery rats (n=30) were randomly assigned to treatment groups of free simvastatin, simvastatin in liposomes (3 mg/kg), and saline (control). Stenosis and neointima to media ratio (N/M) were determined 14 days following single IV injection at the time of injury by morphometric analysis. Depletion of circulating monocytes was determined by flow cytometry analyzes of blood specimens. Inhibition of RAW264.7, J774, and THP-1 proliferation by simvastatinloaded liposomes and free simvastatin was determined by the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay. Simvastatin liposomes were successfully formulated and were found to be 1.5-2 times more potent than the free drug in suppressing the proliferation of monocytes/ macrophages in cell cultures of RAW 264.7, J774, and THP-1. IV injection of liposomal simvastatin to carotid-injured rats (3 mg/kg, n=4) resulted in a transient depletion of circulating monocytes, significantly more prolonged than that observed following treatment with free simvastatin. Administration to ballooninjured rats suppressed neointimal growth. N/M at 14 days was 1.56±0.16 and 0.90±0.12, control and simvastatin liposomes, respectively. One single systemic administration of liposomal simvastatin at the time of injury significantly suppresses neointimal formation in the rat model of restenosis, mediated via a partial and transient depletion of circulating monocytes.

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“…Since our target cells are circulating monocytes, liposome size of 150-250 nm is preferable. This is because, while vesicles larger than 100 nm are eliminated from the blood stream exclusively by monocyte/macrophage uptake (29,30), vesicles under 250 nm can be readily filter-sterilized. A charged membrane enhances the internalization of liposomes into phagocytic cells through adsorptive endocytosis (30,31), and opsonization mediates efficient internalization (32,33).…”

Section: Discussionmentioning

confidence: 99%

Preparation of Alendronate Liposomes for Enhanced Stability and Bioactivity: In Vitro and In Vivo Characterization

Epstein

Gutman

Cohen-Sela

et al. 2008

AAPS J

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Abstract. Liposomes containing bisphosphonates have been shown to deplete circulating monocytes and reduce experimental restenosis. However, acceptable shelf life was not achieved, and the disruption extent and rate of the vesicles in the circulation has not been examined. Designing an optimal liposomal formulation in general, and for an anti-inflammatory effect in particular, requires careful consideration of the factors that contribute to their in vitro stability and integrity in the blood after injection. An improved liposomal alendronate formulation was prepared by a modified thin lipid film hydration technique followed by extrusion, resulting in relatively smaller size vesicles, narrow size distribution, and low drug to lipid ratio in comparison to the reverse phase evaporation method. In order to rule out premature leakage of the drug, the integrity of the vesicles was examined by means of size-exclusion chromatography in vitro and in vivo, with subsequent analysis of size, drug (fractions of encapsulated and free) and lipid concentrations. Vesicles were found to be stable in serum, with 15±3% leakage of the drug after 10 min in rabbit's circulation, and intact liposomes were detected in the circulation 24 h following administration. It is concluded that the new formulation results in increased stability (2.5 years) as determined by the insignificant changes in vesicle size, drug leakage, lipid and drug stability, in vitro bioactivity (macrophages inhibition), as well as in vivo in depleting circulating monocytes and inhibition of restenosis in rabbits. Our in vitro stability results regarding dilution in serum paralleled in vivo data. Thus, in vitro assessment may provide a valuable tool in assessing in vivo integrity of liposomal formulations.

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Interactions of liposomes with the reticuloendothelial system effects of reticuloendothelial blockade on the clearance of large unilamellar vesicles

Cited by 133 publications

References 15 publications

Tissue specific opsonins for phagocytic cells and their different affinity for cholesterol‐rich liposomes

Tissue specific opsonins for phagocytic cells and their different affinity for cholesterol‐rich liposomes

Liposomal Simvastatin Attenuates Neointimal Hyperplasia in Rats

Preparation of Alendronate Liposomes for Enhanced Stability and Bioactivity: In Vitro and In Vivo Characterization

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