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. 1. Introduction Pancreatic adenocarcinoma is the fourth highest cause of cancer death with a 5-year survival rate of less than 6% [1]. Despite the use of surgery, radiation, and/or chemotherapy [2], local recurrence and metastasis invariably occur. The causes of resistance of pancreatic tumors are not completely understood. The inability to deliver adequate adjuvant therapy due to local normal tissue toxicity, limitations caused by tumor microenvironment (hypoxia, pH), and active drug export out of tumor cells likely cause this resistance [3, 4]. Modifications to the delivery of chemotherapeutics that improve the therapeutic ratio (TR) are highly desirable in order to allow higher drug delivery while minimizing toxicity to normal tissues. Gemcitabine is a commonly used water soluble anticancer agent that acts as an antimetabolite; it is considered an efficacious addition to radiation therapy in pancreatic cancer [5]. Gemcitabine is an S-phase deoxycytidine analog (2′,2′-difluorodeoxycytidine). Its mechanism of action involves competitive incorporation into DNA, masked termination (causing termination of DNA synthesis without being excised out of the strand), and self-potentiation (promoting its own activity by inhibiting regulatory enzymes involved in
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