title: Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells.
abstract: Traditional anticancer chemotherapy often displays toxic side effects, poor bioavailability, and a low therapeutic index. Targeting and controlled release of a chemotherapeutic agent can increase drug bioavailability, mitigate undesirable side effects, and increase the therapeutic index. Here we report a polymersome-based system to deliver gemcitabine to Panc-1 cellsin vitro. The polymersomes were self-assembled from a biocompatible and completely biodegradable polymer, poly(ethylene oxide)-poly(caprolactone), PEO-PCL. We showed that we can encapsulate gemcitabine within stable 200 nm vesicles with a 10% loading efficiency. These vesicles displayed a controlled release of gemcitabine with 60% release after 2 days at physiological pH. Upon treatment of Panc-1 cellsin vitro, vesicles were internalized as verified with fluorescently labeled polymersomes. Clonogenic assays to determine cell survival were performed by treating Panc-1 cells with varying concentrations of unencapsulated gemcitabine (FreeGem) and polymersome-encapsulated gemcitabine (PolyGem) for 48 hours. 1μM PolyGem was equivalent in tumor cell toxicity to 1μM FreeGem, with a one log cell kill observed. These studies suggest that further investigation on polymersome-based drug formulations is warranted for chemotherapy of pancreatic cancer.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Nimil
authors.initials: N
authors.lastname: Sood
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Walter T
authors.initials: WT
authors.lastname: Jenkins
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Yang
authors.affiliation: Department of Neuroscience, University of Miami, Coral Gables, FL, USA.
authors.forename: Nikesh N
authors.initials: NN
authors.lastname: Shah
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Katz
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Koch
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Frail
authors.affiliation: Department of Chemistry, Duke University, Durham, NC, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Therien
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA ; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hammer
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Sydney M
authors.initials: SM
authors.lastname: Evans