Polymeric micelles for the pH-dependent controlled, continuous low dose release of paclitaxel Public Deposited

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This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier and can be found at:  http://www.journals.elsevier.com/biomaterials/

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  • Poly(ethylene glycol)-block-poly(aspartate-hydrazide) (PEG-p(Asp-Hyd)) was modified using either levulinic acid (LEV) or 4-acetyl benzoic acid (4AB) attached via hydrazone bonds. Paclitaxel (PTX) conjugated to the linkers formed PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX). PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX) assemble into unimodal polymeric micelles with diameters of 42 nm and 137 nm, respectively. PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX) at a 1:1 and 1:5 molar ratio assemble into unimodal mixed polymeric micelles with diameters of 85 and 113 nm, respectively. PEG-p(Asp-Hyd-LEV-PTX) micelles release LEV-PTX faster at pH 5.0 than at pH 7.4 over 24 h. At pH 7.4 mixed polymeric micelles at 1:5 ratio show no difference in LEV-PTX release from PEG-p(Asp-Hyd-LEV-PTX) micelles. Mixed polymeric micelles at 1:5 molar ratio gradually release LEV-PTX at pH 5.0, with no release of 4AB-PTX. PEG-p(Asp-Hyd-LEV-PTX) micelles and mixed polymeric micelles exert comparable cytotoxicity against SK-OV-3 and MCF-7 cancer cell lines. In summary, mixed polymeric micelles based on PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX) offer prospects for pH-dependent release of PTX, offering a novel prodrug strategy for adjusting its pharmacokinetic and pharmacodynamic properties for cancer therapy. If successful this delivery system offers an alternative new mode of delivery for paclitaxel with a new scope for its efficacy along with a minimal synthetic framework needed to accomplish this.
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  • Alani, A. W. G., Bae, Y., Rao, D. A., & Kwon, G. S. (2010). Polymeric micelles for the pH-dependent controlled, continuous low dose release of paclitaxel. Biomaterials, 31(7), 1765-1772. doi:10.1016/j.biomaterials.2009.11.038
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  • description.provenance : Submitted by Deanne Bruner (deanne.bruner@oregonstate.edu) on 2015-04-15T23:00:59Z No. of bitstreams: 1 AlaniAdamPharmacyPolymericMicelles_pH-DependentControlled.pdf: 1050502 bytes, checksum: 680cf5bf0fc96ee28e19f94e8c4e79b6 (MD5)
  • description.provenance : Made available in DSpace on 2015-04-15T23:01:32Z (GMT). No. of bitstreams: 1 AlaniAdamPharmacyPolymericMicelles_pH-DependentControlled.pdf: 1050502 bytes, checksum: 680cf5bf0fc96ee28e19f94e8c4e79b6 (MD5) Previous issue date: 2010-03
  • description.provenance : Approved for entry into archive by Deanne Bruner(deanne.bruner@oregonstate.edu) on 2015-04-15T23:01:32Z (GMT) No. of bitstreams: 1 AlaniAdamPharmacyPolymericMicelles_pH-DependentControlled.pdf: 1050502 bytes, checksum: 680cf5bf0fc96ee28e19f94e8c4e79b6 (MD5)

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