Tuesday, August 6, 2013

Thermogel FAQ's

I often get quite a few questions on thermogels. A few answers to common ones below:

FAQ: AK12, AK24, AK36, AK48? What are these and what can you tell me about them?
A- "AK12: PLGA-PEG-PLGA (Mn ~1000-1000-1000, 1:1 LA:GA) - this one is the quickest degrading thermogel we have because it is very short and 50:50 LA:GA (which is quick degrading). This one was used in a publication by Zare's group out at Stanford (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489921/) for injecting and holding microparticles.
AK24 PLGA-PEG-PLGA (Mn ~1100-1000-1100, 3:1 LA:GA)  - just a little slower degrading than the AK12 but similar thermogelling properties. Recently published (http://informahealthcare.com/doi/abs/10.3109/03639045.2013.789054) for use for cidofovir delivery.  They actually show decent controlled (almost linear after the burst) release for 100hrs with this one (attached image) (they call it "commercial PEG-PLGA-PEG", they also synthesized another one with higher MW as well).  Although this is a small-molecule, it is highly water soluble (170mg/ml, drugbank) so such a controlled release is still fairly impressive. 
AK36: mPEG-PCL (Mw 750-2500) - This one is a little unique, very slow degrading and a little tricky to dissolve requiring initially 4C followed by 0.5hr at 80C to break up crystalline domains.  This one is suggested for only long-term (several months) delivery.
Additionally there is AK46 (PLA-PEG-PLA 1000-1000-1000) which is also a thermogel. It is similar to AK12/AK24 in gelation but pure lactide so more stable.  AK36 and AK46 are fairly new so there aren't any publications out with them yet."
FAQ: The polyscitech website suggests a solution at 4°C is stable for 2-3 weeks.  Is the gelled form of the solution more stable than the cold aqueous solution?
A- "This is from our users guide (http://www.akinainc.com/pdf/PolyVivo%20AK12-AK24%20thermogelation.pdf) and what is meant by the polymer solution "being stable" in this case is before some degradation has occurred that could change the properties in terms of gelation and longevity in the body (if already partially degraded, may not last as long in testing).  We have noticed AK12/AK24 solutions left in the fridge over a month or two have gelled spontaneously, but the exact timeline on this has not been determined. In a practical sense its best to use solutions fairly soon.  By no means are these more stable heated in gel state than in cold state just simply due to temperature.  Stability for these is just due to hydrolytic degradation so water will start to break-down the chains when in contact but this process is slower at lower temperatures. We provide these as dry solids (which is their most stable form) and I suggest storing them dry and reconstituting close to time of use in water."
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