AJ
If fact I made it sound worse than it is. My intent was to illustrate
that phagoytosis was the natural fate of any liposomes that made it into
the lymph and blood. If a large amount of liposomes got into the system,
then the macrophages would be hard at work eating them up. However, its
difficult to find evidence that intact liposomes make it across the GI
tract, although Peyers patches may transport some into the lymph system.
Overburdening the immune system was not the right description, sorry.
Because liposomes are consumed by macrophages, it is a well known method
to deplete them in vivo by loading liposomes with the drug
dichloromethylene diphosphonate. This is able to wipe out a large
percent of macrophages in the target system. But even unloaded liposomes
can have a dramatic effect on the spleen and liver and immune system
Allen et al performed a detailed study in mice on the effect of chronic
IV administration of liposomes on MPS function.. Decreased uptake of
liposomes into the liver combined with increased uptake into the spleen
were taken as evidence of MPS impairment. Significant depression in
phagocytic index was observed after 2 to 3 IV injections. In the case of
liposomes of rigid composition (PC/SM) considerable spenomegaly was
observed. ...It was suggested that liposomes with rigid bilayers caused
greater impairment than those with fluid bilayers. In addition there wee
granulomatous reaction in the liver. The appearaince of granulomas was
correlated with depression of the phagocytic index.
Similar findings were described earlier by Weereratne et al. IV
injections of 100mg/kg of SM/Chol liposomes led to 50 and 300%
enlargement of the liver and spleen respectively. No such effect was
ovserved after similar treatment with PC/Chol liposomes.
In the opinion of Claassen et al the results of Weereratne and Allen
were not indicative of significant toxicity, but only reflected a
temporary disturbance.
A potential problem with conventional liposomes, particularly when
delivered intravenously, is their rapid removal from circulation by
cells of the reticuloendothelial system particularly in the liver and
spleen. To circumvent the phagocytic cells of the immune system and
hence enhance their half-life in the circulation, “stealth liposomes”
have been designed. Stealth liposomes are created by coating the
liposomes with a layer of polyethylene glycol-phosphatidylethanolamine
(PEG liposomes).
M
On 11/29/2012 12:16 PM, André Juthe wrote:
Do you have any reference for that? I never heard of that, I would
like to read more about it.
/AJ
2012/11/29 mgperrault <mgperra...@aol.com>:
"Any liposomes that get into the blood stream are attacked by macrophages.
One can in fact overburden your immune system this way. So they have
devised stealth liposomes to avoid this."
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