Micelles of Different Morphologies - Advantages of Worm-like Filomicelles of PEO-PCL in Paclitaxel Delivery
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paclitaxel
poly(epsilon-caprolactone)
poly(ethylene oxide)
worm-like micelle
Biochemical and Biomolecular Engineering
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Abstract
Worm-like and spherical micelles are both prepared here from the same amphiphilic diblock copolymer, poly(ethylene oxide)-b-poly (ε-caprolactone) (PEO [5 kDa]-PCL [6.5 kDa]) in order to compare loading and delivery of hydrophobic drugs. Worm-like micelles of this degradable copolymer are nanometers in cross-section and spontaneously assemble to stable lengths of microns, resembling filoviruses in some respects and thus suggesting the moniker "filomicelles". The highly flexible worm-like micelles can also be sonicated to generate kinetically stable spherical micelles composed of the same copolymer. The fission process exploits the finding that the PCL cores are fluid, rather than glassy or crystalline, and core-loading of the hydrophobic anticancer drug delivery, paclitaxel (TAX) shows that the worm-like micelles load and solubilize twice as much drug as spherical micelles. In cytotoxicity tests that compare to the clinically prevalent solubilizer, Cremophor® EL, both micellar carriers are far less toxic, and both types of TAX-loaded micelles also show 5-fold greater anticancer activity on A549 human lung cancer cells. PEO-PCL based worm-like filomicelles appear to be promising pharmaceutical nanocarriers with improved solubilization efficiency and comparable stability to spherical micelles, as well as better safety and efficacy in vitro compared to the prevalent Cremophor® EL TAX formulation.