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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

Cryo-TEM micrographs of PEO-PCL vesicles incubated for 12 hours. (a) pH 7.4. (b)–(d) pH5.0. Arrows indicate areas of membrane degradation. Scale bar = 100 nm.
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Figure 3: Cryo-TEM micrographs of PEO-PCL vesicles incubated for 12 hours. (a) pH 7.4. (b)–(d) pH5.0. Arrows indicate areas of membrane degradation. Scale bar = 100 nm.

Mentions: In order to understand the difference in observed release rate between vesicles at pH 5.0 and 7.4, we observed the structure of nanovesicles using cryo-TEM at the incubation different conditions. Figure 3 provides representative images of vesicles that have been incubated at either pH 7.4 (Figure 3(a)) or pH 5.0 (Figures 3(b)–3(d)) for 12 hours. The vesicles in Figure 3(a) have an even membrane thickness that is an indicative of an intact membrane. The vesicles in Figures 3(b)–3(d) have compromised membranes as shown by the arrows. In Figure 3(b), the membrane of one vesicle has completely disintegrated and has formed a pore. Figure 3(c) shows a vesicle with a thinning portion of the membrane. Finally, in Figure 3(d) we see a membrane pore starting to form.


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)

Cryo-TEM micrographs of PEO-PCL vesicles incubated for 12 hours. (a) pH 7.4. (b)–(d) pH5.0. Arrows indicate areas of membrane degradation. Scale bar = 100 nm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Cryo-TEM micrographs of PEO-PCL vesicles incubated for 12 hours. (a) pH 7.4. (b)–(d) pH5.0. Arrows indicate areas of membrane degradation. Scale bar = 100 nm.
Mentions: In order to understand the difference in observed release rate between vesicles at pH 5.0 and 7.4, we observed the structure of nanovesicles using cryo-TEM at the incubation different conditions. Figure 3 provides representative images of vesicles that have been incubated at either pH 7.4 (Figure 3(a)) or pH 5.0 (Figures 3(b)–3(d)) for 12 hours. The vesicles in Figure 3(a) have an even membrane thickness that is an indicative of an intact membrane. The vesicles in Figures 3(b)–3(d) have compromised membranes as shown by the arrows. In Figure 3(b), the membrane of one vesicle has completely disintegrated and has formed a pore. Figure 3(c) shows a vesicle with a thinning portion of the membrane. Finally, in Figure 3(d) we see a membrane pore starting to form.

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