Breaking down endolysosomal barriers for drug delivery with degradable polymersomes

Fariyal Ahmed, Goundla Srinivas, Aaron Brannan, Michael L. Klein, Frank S. Bates, Dennis E. Discher

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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 languageEnglish (US)
Title of host publication05AIChE
Subtitle of host publication2005 AIChE Annual Meeting and Fall Showcase, Conference Proceedings
Number of pages1
StatePublished - Dec 1 2005
Event05AIChE: 2005 AIChE Annual Meeting and Fall Showcase - Cincinnati, OH, United States
Duration: Oct 30 2005Nov 4 2005

Other

Other05AIChE: 2005 AIChE Annual Meeting and Fall Showcase
CountryUnited States
CityCincinnati, OH
Period10/30/0511/4/05

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