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 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.

Embedding of superparamagnetic iron oxide nanoparticles into membranes of well-defined poly(ethylene oxide)-block-poly(ε-caprolactone) nanoscale magnetovesicles as ultrasensitive MRI probes of membrane bio-degradation

“…The final block copolymer composition is PEO 45 -b-PCL 111 , where 45 and 111 are the respective average degrees of polymerization (DP) of each monomer unit. This composition is close to the target hydrophilic ratio (14% weight fraction) of PEO 45 -b-PCL 105 , which was chosen owing to its tendency to form a vesicular morphology [29,30,32,34,35,37]. The copolymer is characterized by a relatively wide molecular weight dispersity (Ð=M w /M n = 1.35) as indicated by GPC ( Fig.…”

“…Several studies have reported the formation of poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) based vesicles, which are predominantly formed when f EO is between 12 and 28 % [29][30][31][32][33][34][35][36][37][38]. Among the different PEO-b-PCL formulations screened, compositions close to PEO 45 -b-PCL 105 (where 45 and 105 refer to the respective average degree of polymerization of each monomer unit) have been widely reported to form vesicles [29,30,32,34,35]. PEO-b-PCL polymersomes possess a high potential for biomedical applications.…”

“…PEO block is biocompatible and its presence on the surface of nanoparticles reduces their non-specific interactions with plasma proteins which decrease their opsonization and increases their blood plasma circulation time. On the one hand, polymer vesicles made from PEO-based copolymers have been shown to remain intact and circulate for more than one day in rats [35]. On the other hand, PCL block is biodegradable and the hydrolysis of its ester linkages is accelerated in an acidic medium providing a controlled release of drugs at acidic pH [29,35].…”

“…On the one hand, polymer vesicles made from PEO-based copolymers have been shown to remain intact and circulate for more than one day in rats [35]. On the other hand, PCL block is biodegradable and the hydrolysis of its ester linkages is accelerated in an acidic medium providing a controlled release of drugs at acidic pH [29,35]. Until now, studies on PEO-b-PCL vesicles mainly focused on their preparation and characterization methods and/or on the loading and release of drugs.…”