The effects of liposome surface charge and size on the intracellular delivery of clodronate and gallium in vitro
Identifieur interne : 002C08 ( Main/Exploration ); précédent : 002C07; suivant : 002C09The effects of liposome surface charge and size on the intracellular delivery of clodronate and gallium in vitro
Auteurs : Jukka Mönkkönen [Finlande] ; Riitta Valjakka [Finlande] ; Maria Hakasalo [Finlande] ; Arto Urtti [Finlande]Source :
- International Journal of Pharmaceutics [ 0378-5173 ] ; 1994.
English descriptors
- Teeft :
- Cell growth, Chloroquine, Clodronate, Clodronate encapsulated, Dspc, Dspg, Dspg liposomes, Encapsulated, Encapsulated clodronate, Endocytosis, Extrusion, Fibroblast, Gallium, Growth inhibition, Heath, International journal, Intracellular, Intracellular processing, Liposomal, Liposomal clodronate, Liposomal gallium, Liposome, Liposome size, Lysosomotropic, Lysosomotropic agents, Macrophage, Mlvs, Multilamellar, Optimal delivery, Phospholipid, Polycarbonate filters, Present study, Primaquine, Rooijen, Surface charge, Unextruded dspg liposomes, Unilamellar, Unilamellar liposomes, Vesicle, Yolk phosphatidylcholine.
Abstract
Abstract: Clodronate (dichloromethylene bisphosphonate) and gallium in liposomes are macrophage suppressive agents, and thus possibly useful in inflammatory diseases. The effects of liposome surface charge, liposome type, and size on the delivery of these compounds to RAW 264 macrophages and L929 fibroblasts were evaluated by growth inhibition assay in vitro. Unilamellar liposomes with neutral surface charge (100 mol% DSPC) were unable to deliver clodronate or gallium to macrophages, but inclusion of negatively charged DSPG in liposomes provided effective delivery of the compounds. Large multilamellar liposomes with neutral surface charge were also ineffective in delivering clodronate to macrophages. A decrease in the size of unilamellar DSPG liposomes by extrusion did not affect the delivery of the compounds to macrophages, but drastically increased their potency for fibroblasts. For macrophage delivery, unextruded DSPG liposomes prepared by the REV method were found to be the best formulation studied, while extrusion of liposomes broadened the effects to other cell types. Various lysosomotropic agents did not affect the potency of liposomal clodronate for macrophages, but decreased the potency of liposomal gallium, indicating that, despite their similarities in mechanism of action in macrophages, the intracellular processing of liposomal clodronate differs from that of gallium.
Url:
DOI: 10.1016/0378-5173(94)90433-2
Affiliations:
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Le document en format XML
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<term>Dspc</term>
<term>Dspg</term>
<term>Dspg liposomes</term>
<term>Encapsulated</term>
<term>Encapsulated clodronate</term>
<term>Endocytosis</term>
<term>Extrusion</term>
<term>Fibroblast</term>
<term>Gallium</term>
<term>Growth inhibition</term>
<term>Heath</term>
<term>International journal</term>
<term>Intracellular</term>
<term>Intracellular processing</term>
<term>Liposomal</term>
<term>Liposomal clodronate</term>
<term>Liposomal gallium</term>
<term>Liposome</term>
<term>Liposome size</term>
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<term>Lysosomotropic agents</term>
<term>Macrophage</term>
<term>Mlvs</term>
<term>Multilamellar</term>
<term>Optimal delivery</term>
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<term>Polycarbonate filters</term>
<term>Present study</term>
<term>Primaquine</term>
<term>Rooijen</term>
<term>Surface charge</term>
<term>Unextruded dspg liposomes</term>
<term>Unilamellar</term>
<term>Unilamellar liposomes</term>
<term>Vesicle</term>
<term>Yolk phosphatidylcholine</term>
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<front><div type="abstract" xml:lang="en">Abstract: Clodronate (dichloromethylene bisphosphonate) and gallium in liposomes are macrophage suppressive agents, and thus possibly useful in inflammatory diseases. The effects of liposome surface charge, liposome type, and size on the delivery of these compounds to RAW 264 macrophages and L929 fibroblasts were evaluated by growth inhibition assay in vitro. Unilamellar liposomes with neutral surface charge (100 mol% DSPC) were unable to deliver clodronate or gallium to macrophages, but inclusion of negatively charged DSPG in liposomes provided effective delivery of the compounds. Large multilamellar liposomes with neutral surface charge were also ineffective in delivering clodronate to macrophages. A decrease in the size of unilamellar DSPG liposomes by extrusion did not affect the delivery of the compounds to macrophages, but drastically increased their potency for fibroblasts. For macrophage delivery, unextruded DSPG liposomes prepared by the REV method were found to be the best formulation studied, while extrusion of liposomes broadened the effects to other cell types. Various lysosomotropic agents did not affect the potency of liposomal clodronate for macrophages, but decreased the potency of liposomal gallium, indicating that, despite their similarities in mechanism of action in macrophages, the intracellular processing of liposomal clodronate differs from that of gallium.</div>
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