miz_sunshine87
12-26-2006, 08:47 PM
I'm not sure if this has already been posted, so if it has feel free to ignore it...
So there was this study done in 2004, where the researchers tested cytotek (aka misoprostol) instillations on rats that had (chemical induced) cystitis. The researchers also developed this new "thermo-sensitive hydrogel" solution in which they delivered the cytotek into the bladders. So they studied the rats for 24 hrs (this part is a bit confusing to me), but basically they discovered that the cytotek stayed in the bladder a lot longer when it was in the hydrogel base (rather than saline), and when they looked at the bladders under a microscope they saw that the bladders threated with the cytotek/hydrogel looked almost normal! The ones that were treated with only cytotek, or only the hydrogel were damaged, but not too badly, and the ones that only got saline solution were a total mess.
Here is the link to the abstract of the study:
http://www.springerlink.com/content/q577930u3031u513/
and here is the full paper:
http://www.springerlink.com/content/q577930u3031u513/fulltext.pdf
Here are a few points that I found in the paper that I found interesting:
(misoprostol) is difficult to formulate due to its
chemical instability. Misoprostol rapidly de-esterifies to its
active form, misoprostolic acid, after oral administration, and
is excreted in urine as its inactive metabolites with an elimination
half-life of approximately 30 min. ---> this is why cytotek probably doesn't work for many people. Thinking back to high school science class, I know that a half-life refers to how long it takes for something to become ineffective...well 30 mins doesn't sound very good to me.
Histological assessment...revealed severe ulcerative cystitis in
the saline-instilled rats after cyclophosphamide injection.
Epithelium was denuded leaving an ulcerated area with
submucosal edema, inflammation, and vascular ectasia and
congestion. In tissue sections obtained from rats treated with
misoprostol and hydrogel separately, hisotological
changes were less severe, which included infiltration
of inflammatory cells and edema of subepithelial tissue
layer responsible for its slightly enlarged appearance. Treatment
with misoprostol in hydrogel showed drastic improvement,
which was evident by lack of any ulcerations in the
normal appearing epithelium with slightly enlarged appearance. --> just explains what the bladders looked like after the different treatments.
conventional vehicles used for the intravesical
route of administration fail to provide a sustained exposure of
drug to the urothelium. Duration of exposure for instilled
drugs does not last beyond the first voiding of urine after
instillation. Increase in efficacy of drugs used for intravesical
therapy would be expected if the duration for direct contact
between the drug and the abnormal urothelium were increased--> explains why instilations are not as sucessful as they could be...they get peed out really soon.
To answer the question, whether a drug entrapped in the
hydrogel is available for its therapeutic action, we tested intravesical
misoprostol in a rat model of cyclophosphamide
cystitis. A previous study done on the same model reported
reduction in cyclophosphamide induced ulceration, inflammation,
and edema in bladder walls of male rat following long
term oral administration of misoprostol (19). A daily oral
dose of 600 _g administered chronically for 3 months was also
effective in patients with refractory interstitial cystitis (20). In
this study, we chose to use a fraction of the oral dose of
misoprostol for a single intravesical administration in the
same rat model of cystitis.--> they're talking about us :smile tee
The beneficial
effect observed in rats instilled with hydrogel itself without
any drug might be a consequent of its emollient properties as
hydrogel with similar composition have shown excellent
wound dressing activity (21). It is possible that intravesically
administered hydrogel might help in healing of ulcers induced
by cyclophosphamide, and wound-healing effect of hydrogel
might underlie the benefit seen in Fig. 3.--> talks about why the hydrogel itself might be helpful for cystitis (sounds like it works like a coating)
This paper describes the first successful use of a modified
thermosensitive PEG-PLGA-PEG polymer as a suitable matrix
for sustained drug delivery by intravesical route. Modifications
introduced into the polymer in our lab enable the
sol-gel transformation of this thermosensitive polymer to occur
even in the presence of typical urine constituents, urea,
and excess electrolytes to extend its application for intravesical
therapy of bladder diseases. Safe and long-acting intravesical
delivery of misoprostol may be a desirable new treatment
of interstitial cystitis. However, further safety studies of
the polymer following intravesical instillation are needed before
it becomes a clinically feasible drug delivery system.--> they're talking about us again :smile tee
[I]So this stuff sounds pretty cool to me. I think its pretty crazy that they were testing the stuff using cytotek...as far as I knew, no one thought of cytotek as a treatment for IC. Actually, it still is not an approved treatment for IC, so where did these guys get the idea from (maybe they're just smart lol)
Does anyone know if they have done more tests on this stuff? I understand that they can't just go instilling this stuff into humans without further testing, but it really sucks that so many people must suffer in the meantime, if this stuff could really be the "magic pill" (so to speak). Heres to hoping that it is, and will be available soon!
So there was this study done in 2004, where the researchers tested cytotek (aka misoprostol) instillations on rats that had (chemical induced) cystitis. The researchers also developed this new "thermo-sensitive hydrogel" solution in which they delivered the cytotek into the bladders. So they studied the rats for 24 hrs (this part is a bit confusing to me), but basically they discovered that the cytotek stayed in the bladder a lot longer when it was in the hydrogel base (rather than saline), and when they looked at the bladders under a microscope they saw that the bladders threated with the cytotek/hydrogel looked almost normal! The ones that were treated with only cytotek, or only the hydrogel were damaged, but not too badly, and the ones that only got saline solution were a total mess.
Here is the link to the abstract of the study:
http://www.springerlink.com/content/q577930u3031u513/
and here is the full paper:
http://www.springerlink.com/content/q577930u3031u513/fulltext.pdf
Here are a few points that I found in the paper that I found interesting:
(misoprostol) is difficult to formulate due to its
chemical instability. Misoprostol rapidly de-esterifies to its
active form, misoprostolic acid, after oral administration, and
is excreted in urine as its inactive metabolites with an elimination
half-life of approximately 30 min. ---> this is why cytotek probably doesn't work for many people. Thinking back to high school science class, I know that a half-life refers to how long it takes for something to become ineffective...well 30 mins doesn't sound very good to me.
Histological assessment...revealed severe ulcerative cystitis in
the saline-instilled rats after cyclophosphamide injection.
Epithelium was denuded leaving an ulcerated area with
submucosal edema, inflammation, and vascular ectasia and
congestion. In tissue sections obtained from rats treated with
misoprostol and hydrogel separately, hisotological
changes were less severe, which included infiltration
of inflammatory cells and edema of subepithelial tissue
layer responsible for its slightly enlarged appearance. Treatment
with misoprostol in hydrogel showed drastic improvement,
which was evident by lack of any ulcerations in the
normal appearing epithelium with slightly enlarged appearance. --> just explains what the bladders looked like after the different treatments.
conventional vehicles used for the intravesical
route of administration fail to provide a sustained exposure of
drug to the urothelium. Duration of exposure for instilled
drugs does not last beyond the first voiding of urine after
instillation. Increase in efficacy of drugs used for intravesical
therapy would be expected if the duration for direct contact
between the drug and the abnormal urothelium were increased--> explains why instilations are not as sucessful as they could be...they get peed out really soon.
To answer the question, whether a drug entrapped in the
hydrogel is available for its therapeutic action, we tested intravesical
misoprostol in a rat model of cyclophosphamide
cystitis. A previous study done on the same model reported
reduction in cyclophosphamide induced ulceration, inflammation,
and edema in bladder walls of male rat following long
term oral administration of misoprostol (19). A daily oral
dose of 600 _g administered chronically for 3 months was also
effective in patients with refractory interstitial cystitis (20). In
this study, we chose to use a fraction of the oral dose of
misoprostol for a single intravesical administration in the
same rat model of cystitis.--> they're talking about us :smile tee
The beneficial
effect observed in rats instilled with hydrogel itself without
any drug might be a consequent of its emollient properties as
hydrogel with similar composition have shown excellent
wound dressing activity (21). It is possible that intravesically
administered hydrogel might help in healing of ulcers induced
by cyclophosphamide, and wound-healing effect of hydrogel
might underlie the benefit seen in Fig. 3.--> talks about why the hydrogel itself might be helpful for cystitis (sounds like it works like a coating)
This paper describes the first successful use of a modified
thermosensitive PEG-PLGA-PEG polymer as a suitable matrix
for sustained drug delivery by intravesical route. Modifications
introduced into the polymer in our lab enable the
sol-gel transformation of this thermosensitive polymer to occur
even in the presence of typical urine constituents, urea,
and excess electrolytes to extend its application for intravesical
therapy of bladder diseases. Safe and long-acting intravesical
delivery of misoprostol may be a desirable new treatment
of interstitial cystitis. However, further safety studies of
the polymer following intravesical instillation are needed before
it becomes a clinically feasible drug delivery system.--> they're talking about us again :smile tee
[I]So this stuff sounds pretty cool to me. I think its pretty crazy that they were testing the stuff using cytotek...as far as I knew, no one thought of cytotek as a treatment for IC. Actually, it still is not an approved treatment for IC, so where did these guys get the idea from (maybe they're just smart lol)
Does anyone know if they have done more tests on this stuff? I understand that they can't just go instilling this stuff into humans without further testing, but it really sucks that so many people must suffer in the meantime, if this stuff could really be the "magic pill" (so to speak). Heres to hoping that it is, and will be available soon!