Abstract
Carrier-mediated entry of cytotoxic drugs into a cell's cytoplasm is often limited by release from the carrier as well as endosomal release after internalization. Here we demonstrate by molecular simulation and experiment that degradable, non-ionic polymersomes of PEG-(polyester) foster endosome rupture and release of cytotoxic drugs doxorubicin (DOX) and paclitaxel (TAX). These drugs are typical soluble and insoluble - anticancer agents. We characterize the stability, delivery and intracellular toxicity of DOX- and TAX-loaded nano-polymersomes with breast and lung cancer cell lines that take up the vesicles. While degradable polymersome formulations retain their load for over a month at 4°C, they exhibit facilitated release at 37°C and low pH. Copolymer degradation fosters endosomal escape through copolymer-induced disruption of the lipid membrane, enhancing intracellular drug release and cytotoxicity up to 40-fold relative to free drug. More generally, the results show that macro-surfactants, which are increasingly being applied, will interact with cell membranes.
Original language | English (US) |
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Title of host publication | 05AIChE |
Subtitle of host publication | 2005 AIChE Annual Meeting and Fall Showcase, Conference Proceedings |
Number of pages | 1 |
State | Published - Dec 1 2005 |
Event | 05AIChE: 2005 AIChE Annual Meeting and Fall Showcase - Cincinnati, OH, United States Duration: Oct 30 2005 → Nov 4 2005 |
Other
Other | 05AIChE: 2005 AIChE Annual Meeting and Fall Showcase |
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Country/Territory | United States |
City | Cincinnati, OH |
Period | 10/30/05 → 11/4/05 |