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2021-10-04 08:00:00
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Paclitaxel prodrug enhances anticancer efficacy

University of Wisconsin (WARF)

A new formulation of paclitaxel fuses the drug to an oligo-lactic acid (oLA) encapsulated in a PEG-PLA micelle.

The inventor tested a number of oLA-paclitaxel molecules in-vitro, including a formulation using a single lactic acid, up to a polymer of 16 lactic acids, fused to paclitaxel. He found that the 8-mer (o(LA)8-paclitaxel) showed efficient micelle loading while maintaining strong tumor cytotoxicity, while longer polymers didn’t result in much better cytotoxicity, but did result in worse drug loading into the micelle.

o(LA)8-paclitaxel has increased loading, enhanced stability and slow release from PEG-PLA micelles relative to micellar paclitaxel (paclitaxel-PM) in vitro. Accordingly, o(LA)8-paclitaxel delivered by PEG-PLA micelles at 20 mg/kg has superior anticancer efficacy relative to paclitaxel-PM at 20 mg/kg in a mouse xenograft model of lung cancer, as well as in a breast xenograft tumor model. Both models do not show difference in relative body weight versus mice treated with paclitaxel-PM.

These findings are promising because typically prodrugs are less effective than the parent molecule.

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MIDWEST DRUG DEVELOPMENT CONFERENCE
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Oct. 4-5, 2021

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