Polymeric micelles made out of amphiphilic block copolymers containing hydrophilic polyethylene glycol attached to hydrophobic biodegradable polyester blocks, such as PEG-PLA or PEG-PCL, can act in self-assembled form as drug delivery systems (DDSs) with proved clinical efficiency. Notably, PEG-PLA micelles with diameter around 25 nm encapsulating paclitaxel (Genexol-PM) were approved in Korea (and are under advanced clinical trials in the U.S.) for the management of metastatic non-small-cell lung cancer, breast cancer and ovarian cancer. Genexol-PM has a lower toxicity and a maximum tolerated dose (MTD) 2-3 times higher than Taxol (paclitaxel in Cremophor EL). However, plasma pharmacokinetics of Genexol PM is not much different than Taxol®, and significant side effects such as peripheral neuropathy, skin rashes, hematologic toxicity, anemia and myalgia are frequently associated with their use. We optimized a set of PEG-PBO-PCL block copolymers with tuned interfaces (block sizes), as DDSs for docetaxel for treating breast cancer. We are presenting evidence that it is possible to stabilize the polymeric micelles in circulation, while still allowing their degradation or even decreasing their stability at tumor sites over-expressing specific esterases (selective stability). We will show how engineering these interfaces can significantly enhance chemotherapeutic drug docetaxel loading and improve the release profile of the novel polymeric DDSs, focusing it on the tumor site, further enhancing MTD and reducing tumor resistance in a synergistic manner.

Interfacial-engineered self-assembled block copolymer micelles for efficient docetaxel delivery in breast cancer therapy

ACS Spring 2022

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