title: Development and in vitro characterization of paclitaxel and docetaxel loaded into hydrophobically derivatized hyperbranched polyglycerols.
abstract: In this study we report the development and in vitro characterization of paclitaxel (PTX) and docetaxel (DTX) loaded into hydrophobically derivatized hyperbranched polyglycerols (HPGs). Several HPGs derivatized with hydrophobic groups (C(8/10) alkyl chains) (HPG-C(8/10)-OH) and/or methoxy polyethylene glycol (MePEG) chains (HPG-C(8/10)-MePEG) were synthesized. PTX or DTX were loaded into these polymers by a solvent evaporation method and the resulting nanoparticle formulations were characterized in terms of size, drug loading, stability, release profiles, cytotoxicity, and cellular uptake. PTX and DTX were found to be chemically unstable in unpurified HPGs and large fractions (∼80%) of the drugs were degraded during the preparation of the formulations. However, both PTX and DTX were found to be chemically stable in purified HPGs. HPGs possessed hydrodynamic radii of less than 10nm and incorporation of PTX or DTX did not affect their size. The release profiles for both PTX and DTX from HPG-C(8/10)-MePEG nanoparticles were characterized by a continuous controlled release with little or no burst phase of release. In vitro cytotoxicity evaluations of PTX and DTX formulations demonstrated a concentration-dependent inhibition of proliferation in KU7 cell line. Cellular uptake studies of rhodamine-labeled HPG (HPG-C(8/10)-MePEG(13)-TMRCA) showed that these nanoparticles were rapidly taken up into cells, and reside in the cytoplasm without entering the nuclear compartment and were highly biocompatible with the KU7 cells.
authors.affiliation: Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
authors.forename: C
authors.initials: C
authors.lastname: Mugabe
authors.forename: R T
authors.initials: RT
authors.lastname: Liggins
authors.forename: D
authors.initials: D
authors.lastname: Guan
authors.forename: I
authors.initials: I
authors.lastname: Manisali
authors.forename: I
authors.initials: I
authors.lastname: Chafeeva
authors.forename: D E
authors.initials: DE
authors.lastname: Brooks
authors.forename: M
authors.initials: M
authors.lastname: Heller
authors.forename: J K
authors.initials: JK
authors.lastname: Jackson
authors.forename: H M
authors.initials: HM
authors.lastname: Burt
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D001692:Biological Transport; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005990:Glycerol / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D015394:Molecular Structure; D036103:Nanotechnology; D017239:Paclitaxel / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D043823:Taxoids / Q000737:chemistry* / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel; C043941:polyglycerol; D017239:Paclitaxel; D005990:Glycerol