Growth Inhibition of Macrophage-Like and Other Cell Types by Liposome-Encapsulated, Calcium-Bound, and Free BisphosphonatesIn Vitro
作者:
MönkkönenJukka,
TaskinenMarkku,
AuriolaSeppo O.K.,
UrttiArto,
期刊:
Journal of Drug Targeting
(Taylor Available online 1994)
卷期:
Volume 2,
issue 4
页码: 299-308
ISSN:1061-186X
年代: 1994
DOI:10.3109/10611869409015910
出版商: Taylor&Francis
关键词: Bisphosphonates;Liposomes;Calcium;Macrophages;Autoimmune disease
数据来源: Taylor
摘要:
AbstractBisphosphonates effectively inhibit osteoclastic bone resorption in diseases characterized by excessive bone loss. Liposome-encapsulated clodronate (dichloromethylene bisphosphonate) also is known to inactivate phagocytic cellsin vivo, and inhibit the growth of macrophage-like RAW 264 cellsin vitro. The macrophage suppressive effect of liposomal clodronate is of interest in autoimmune diseases, like rheumatoid arthritis, in which phagocytic cells are involved in inflammatory processes. Earlierin vivostudies suggested that liposomal clodronate is a far more potent inactivator of macrophages than liposomal forms of two other bisphosphonate compounds, pamidronate (3-amino-l-hydroxypropylidene bisphosphonate), and etidronate (l-hydroxyethylidene-l, l-bisphosphonate). We examined the growth inhibitory properties of these three bisphosphonates with macrophage-like RAW 264 cells and with other types of cellsin vitro. All three bisphosphonates encapsulated in liposomes effectively inhibited the growth of RAW 264 and CV1-P cells, while free drugs were 20-1000 times less potent growth inhibitors. Also, high extracellular calcium concentrations enhanced the potency of bisphosphonates for RAW 264 cells, indicating that, in addition to liposomes, the uptake of bisphosphonates by macrophages is mediated also by calcium. In all formulations, pamidronate was the most potent compound for the cells, with the exception of CV1-P cells, for which liposomal clodronate was the most potent. The effects of liposomal drugs were selective for highly endocytotic cells. The results suggest that liposome-encapsulated bisphosphonates could provide a specific tool to affect the function of macrophages and all three of these bisphosphonates are potentially effective as macrophage suppressors in autoimmune diseases.
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