Within the presented project, we designed and synthesized a new delivery system for the anticancer drug doxorubicin based on a poly(2-ethyl-2-oxazoline) (PEtOx) carrier with linear architecture and narrow molar mass distribution. The drug is connected to the polymer backbone via an acid-sensitive hydrazone linker, which allows its triggered release in the tumor. The in vitro studies demonstrate successful cellular uptake of conjugates followed by release of the cytostatic cargo. In vivo experiments in EL4 lymphoma bearing mice revealed prolonged blood circulation, increased tumor accumulation and enhanced anticancer properties of the PEtOx conjugate having higher molecular weight (40 kDa) compared to the lower molecular weight (20 kDa) polymer. A similar study was performed using the system based on even more hydrophilic poly(2-methyl-2-oxazoline) carrier. Considering the synthetic advantages of poly(2-alkyl-2-oxazoline)s, the presented study demonstrates their potential as a versatile alternative to well-known PEO- or PHPMA-based materials for the construction of drug delivery systems.

Poly(2-alkyl-2-oxazoline) conjugates of doxorubicin bound via pH-sensitive hydrazone linker: Synthesis, in vitro, and in vivo evaluation

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.