Micelles of Different Morphologies—Advantages of Worm-like Filomicelles of PEO-PCL in Paclitaxel Delivery
- 1.5k Downloads
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.
Materials and Methods
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 fivefold 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.
Key wordslung carcinoma cells paclitaxel poly(ɛ-caprolactone) poly(ethylene oxide) worm-like micelle
- 12.J. Wang, D. Mongayt, and V. P. Torchilin. Polymeric micelles for delivery of poorly soluble drugs: preparation and anticancer activity in vitro of paclitaxel incorporated into mixed micelles based on poly(ethylene glycol)–lipid conjugate and positively charged lipids. J. Drug Target. 13:73–80 (2005).PubMedCrossRefGoogle Scholar
- 15.T. Y. Kim, D. W. Kim, J. Y. Chung, S. G. Shin, S. C. Kim, D. S. Heo, N. K. Kim, and Y. J. Bang. Phase I and pharmacokinetic study of Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clin. Cancer Res. 10:3708–3716 (2004).PubMedCrossRefGoogle Scholar
- 22.T. Meyer, D. Waidelich, and A. W. Frahm. Separation and first structure elucidation of Cremophor EL-components by hyphenated capillary electrophoresis and delayed extraction-matrix assisted laser desorption/ionization-time of flight-mass spectrometry. Electrophoresis. 23:1053–1062 (2002).PubMedCrossRefGoogle Scholar
- 33.Y. Geng, F. Ahmed, N. Bhasin, and D. E. Discher. Visualizing worm micelle dynamics and phase transitions of a charged diblock copolymer in water. J. Phys. Chem., B Condens. Mater. Surf. Interfaces Biophys. 109:3772–3779 (2005).Google Scholar
- 43.G. L. Li and J. X. Tang. Diffusion of actin filaments within a thin layer between two walls. Phys. Rev., E Stat. Nonlin. Soft Matter Phys. 69: Art. No. 061921 Part 1:(2004).Google Scholar