Limits...
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

PolyGem internalization by Panc-1 cells. (a) Fluorescence intensity of PZn3-polymersomes internalized by cells in well plates corresponding to 48 hour time point. (b) Concentration of PZn3 uptake as a function of solution PZn3 concentration (n = 3). Error bars indicate standard deviation. (c) CLSM z-stack images of Panc-1 cells incubated with PZn3-polymersomes for 12 hours. Z-slices (Δz = 3 μm) are presented from left to right. Scale bar = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4496003&req=5

Figure 4: PolyGem internalization by Panc-1 cells. (a) Fluorescence intensity of PZn3-polymersomes internalized by cells in well plates corresponding to 48 hour time point. (b) Concentration of PZn3 uptake as a function of solution PZn3 concentration (n = 3). Error bars indicate standard deviation. (c) CLSM z-stack images of Panc-1 cells incubated with PZn3-polymersomes for 12 hours. Z-slices (Δz = 3 μm) are presented from left to right. Scale bar = 50 μm.

Mentions: We visualized polymersome internalization by a cellular uptake study of blank polymersomes loaded with a hydrophobic porphyrin-based NIR fluorophore, PZn3, in the vesicle membrane. In our study, Panc-1 cells were incubated with 50, 250, or 500 nM of PZn3-loaded polymersomes in 96-well plates for 12, 24, or 48-hours. A calibration was performed to relate the integrated intensity in wells to PZn3 concentration. Figure 4 shows the concentration of internalized PZn3 as a function of incubation time. Vesicle uptake increased with an increase in the concentration of PZn3 as well as incubation time. In order to confirm that the internalization from the uptake study was not surface association, Panc-1 cells were incubated with 500 nM PZn3 for 12 hours and imaged on a confocal microscope with 1 μm z-slices. Figure 4(c) shows z-slices starting from the top of the cell and moving to the bottom. Vesicles are only observed internally and not on the cell surface.


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)

PolyGem internalization by Panc-1 cells. (a) Fluorescence intensity of PZn3-polymersomes internalized by cells in well plates corresponding to 48 hour time point. (b) Concentration of PZn3 uptake as a function of solution PZn3 concentration (n = 3). Error bars indicate standard deviation. (c) CLSM z-stack images of Panc-1 cells incubated with PZn3-polymersomes for 12 hours. Z-slices (Δz = 3 μm) are presented from left to right. Scale bar = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: PolyGem internalization by Panc-1 cells. (a) Fluorescence intensity of PZn3-polymersomes internalized by cells in well plates corresponding to 48 hour time point. (b) Concentration of PZn3 uptake as a function of solution PZn3 concentration (n = 3). Error bars indicate standard deviation. (c) CLSM z-stack images of Panc-1 cells incubated with PZn3-polymersomes for 12 hours. Z-slices (Δz = 3 μm) are presented from left to right. Scale bar = 50 μm.
Mentions: We visualized polymersome internalization by a cellular uptake study of blank polymersomes loaded with a hydrophobic porphyrin-based NIR fluorophore, PZn3, in the vesicle membrane. In our study, Panc-1 cells were incubated with 50, 250, or 500 nM of PZn3-loaded polymersomes in 96-well plates for 12, 24, or 48-hours. A calibration was performed to relate the integrated intensity in wells to PZn3 concentration. Figure 4 shows the concentration of internalized PZn3 as a function of incubation time. Vesicle uptake increased with an increase in the concentration of PZn3 as well as incubation time. In order to confirm that the internalization from the uptake study was not surface association, Panc-1 cells were incubated with 500 nM PZn3 for 12 hours and imaged on a confocal microscope with 1 μm z-slices. Figure 4(c) shows z-slices starting from the top of the cell and moving to the bottom. Vesicles are only observed internally and not on the cell surface.

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