Thursday, July 16, 2015

PolySciTech mPEG-PLA used for enhancing resveratrol circulation time in blood-stream

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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