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Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells.

Sood N, Jenkins WT, Yang XY, Shah NN, Katz JS, Koch CJ, Frail PR, Therien MJ, Hammer DA, Evans SM - J Pharm (Cairo) (2013)

Bottom Line: Targeting and controlled release of a chemotherapeutic agent can increase drug bioavailability, mitigate undesirable side effects, and increase the therapeutic index.The polymersomes were self-assembled from a biocompatible and completely biodegradable polymer, poly(ethylene oxide)-poly(caprolactone), PEO-PCL.These studies suggest that further investigation on polymersome-based drug formulations is warranted for chemotherapy of pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.

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 cells in 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 cells in 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. 1 μM PolyGem was equivalent in tumor cell toxicity to 1 μM 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.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of PolyGem. In aqueous solution, poly(ethylene oxide)-b-poly(caprolactone) (PEO-PCL) self-assemble into spherical polymer vesicles (polymersomes), with the hydrophobic PCL chains orienting end to end to form the bilayer. The figure represents a uniaxial cross section of the polymersome, with gemcitabine () encapsulated in the aqueous lumen. Vesicles can also be made to include PZn3 (○) in the hydrophobic membrane.
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Figure 1: Schematic representation of PolyGem. In aqueous solution, poly(ethylene oxide)-b-poly(caprolactone) (PEO-PCL) self-assemble into spherical polymer vesicles (polymersomes), with the hydrophobic PCL chains orienting end to end to form the bilayer. The figure represents a uniaxial cross section of the polymersome, with gemcitabine () encapsulated in the aqueous lumen. Vesicles can also be made to include PZn3 (○) in the hydrophobic membrane.

Mentions: Figure 1 shows a schematic of our novel carrier. The size distribution of vesicles was measured using dynamic light scattering (DLS) and is shown in Table 1. Vesicles were serially extruded through 400, 200, 100, 100, and 200 nm polycarbonate membranes to reduce the sample polydispersity. The average hydrodynamic diameter of PolyGems was 180 nm. The hydrodynamic diameter of blank polymersomes (181 nm) and PZn3-polymersomes (180 nm) did not statistically vary from PolyGems (P > 0.05). Vesicles were stored at 4°C and used in the studies within one week of preparation. We evaluated the stability of gemcitabine after sonication and freeze/thaw cycles by checking the absorbance of the drug before and after processing. There was no difference in the absorbance spectrum, indicating that the drug retained its structure.


Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells.

Sood N, Jenkins WT, Yang XY, Shah NN, Katz JS, Koch CJ, Frail PR, Therien MJ, Hammer DA, Evans SM - J Pharm (Cairo) (2013)

Schematic representation of PolyGem. In aqueous solution, poly(ethylene oxide)-b-poly(caprolactone) (PEO-PCL) self-assemble into spherical polymer vesicles (polymersomes), with the hydrophobic PCL chains orienting end to end to form the bilayer. The figure represents a uniaxial cross section of the polymersome, with gemcitabine () encapsulated in the aqueous lumen. Vesicles can also be made to include PZn3 (○) in the hydrophobic membrane.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496003&req=5

Figure 1: Schematic representation of PolyGem. In aqueous solution, poly(ethylene oxide)-b-poly(caprolactone) (PEO-PCL) self-assemble into spherical polymer vesicles (polymersomes), with the hydrophobic PCL chains orienting end to end to form the bilayer. The figure represents a uniaxial cross section of the polymersome, with gemcitabine () encapsulated in the aqueous lumen. Vesicles can also be made to include PZn3 (○) in the hydrophobic membrane.
Mentions: Figure 1 shows a schematic of our novel carrier. The size distribution of vesicles was measured using dynamic light scattering (DLS) and is shown in Table 1. Vesicles were serially extruded through 400, 200, 100, 100, and 200 nm polycarbonate membranes to reduce the sample polydispersity. The average hydrodynamic diameter of PolyGems was 180 nm. The hydrodynamic diameter of blank polymersomes (181 nm) and PZn3-polymersomes (180 nm) did not statistically vary from PolyGems (P > 0.05). Vesicles were stored at 4°C and used in the studies within one week of preparation. We evaluated the stability of gemcitabine after sonication and freeze/thaw cycles by checking the absorbance of the drug before and after processing. There was no difference in the absorbance spectrum, indicating that the drug retained its structure.

Bottom Line: Targeting and controlled release of a chemotherapeutic agent can increase drug bioavailability, mitigate undesirable side effects, and increase the therapeutic index.The polymersomes were self-assembled from a biocompatible and completely biodegradable polymer, poly(ethylene oxide)-poly(caprolactone), PEO-PCL.These studies suggest that further investigation on polymersome-based drug formulations is warranted for chemotherapy of pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.

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 cells in 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 cells in 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. 1 μM PolyGem was equivalent in tumor cell toxicity to 1 μM 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.

No MeSH data available.


Related in: MedlinePlus