PolySciTech (www.polyscitech.com) provides a wide
array of block copolymers including mPEG-P(DL)La. Resveratrol is a naturally occurring
chemical derived from plants that has been report to have many biological
effects including chemoprevention and anti-oxidant activity. However, use of
this medicine is difficult as this molecule does not last long inside the human
body as it is metabolized to an inactive form rapidly (half-life < 8
minutes). Recently, researchers at Curtin University utilized mPEG-PLA from
PolyScitech (PolyVivo AK084) as a starting molecule to graft a biodegradable PEG
chain onto the resveratrol so as to improve its longevity in the blood stream.
This molecule was tested in rodents and the half-life was observed to increase
from < 8 minutes to 3 hours giving the resveratrol a longer time span over
which it could express its pharmaceutical activity. Read more: Siddalingappa B,
Benson HAE, Brown DH, Batty KT, Chen Y (2015) Stabilization of Resveratrol in
Blood Circulation by Conjugation to mPEG and mPEG-PLA Polymers: Investigation
of Conjugate Linker and Polymer Composition on Stability, Metabolism, Antioxidant
Activity and Pharmacokinetic Profile. PLoS ONE 10(3): e0118824.
doi:10.1371/journal.pone.0118824 http://dx.plos.org/10.1371/journal.pone.0118824
“Abstract: Resveratrol is naturally occurring
phytochemical with diverse biological activities such as chemoprevention,
anti-inflammatory, anti-cancer, anti-oxidant. But undergoes rapid metabolism in
the body (half life 0.13h). Hence Polymer conjugation utilizing different
chemical linkers and polymer compositions was investigated for enhanced
pharmacokinetic profile of resveratrol. Ester conjugates such as
α-methoxy-ω-carboxylic acid poly(ethylene glycol) succinylamide resveratrol
(MeO-PEGN-Succ-RSV) (2 and 20 kDa); MeO-PEG succinyl ester resveratrol
(MeO-PEGO-Succ-RSV) (2 kDa); α-methoxy poly(ethylene glycol)-co-polylactide
succinyl ester resveratrol (MeO-PEG-PLAO-Succ-RSV) (2 and 6.6kDa) were prepared
by carbodiimide coupling reactions. Resveratrol-PEG ethers (2 and 5 kDa) were
synthesized by alkali-mediated etherification. All polymer conjugates were
fully characterized in vitro and the pharmacokinetic profile of selected
conjugates was characterized in rats. Buffer and plasma stability of conjugates
was dependent on polymer hydrophobicity, aggregation behavior and PEG corona,
with MeO-PEG-PLAO-Succ-RSV (2 kDa) showing a 3h half-life in rat plasma in
vitro. Polymer conjugates irrespective of linker chemistry protected
resveratrol against metabolism in vitro. MeO-PEG-PLAO-Succ-RSV (2 kDa),
Resveratrol-PEG ether (2 and 5 kDa) displayed improved pharmacokinetic profiles
with significantly higher plasma area under curve (AUC), slower clearance and
smaller volume of distribution, compared to resveratrol.”
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