Lipase-catalyzed synthesis of pH-responsive poly(β-thioether ester)-b-poly(ethylene glycol)-b-poly(β-thioether ester) amphiphilic triblock copolymers for drug delivery

Abstract

Novel amphiphilic triblock copolymers poly(β-thioether ester)-b-poly(ethylene glycol)-b-poly(β-thioether ester) (PTE-b-PEG-b-PTE) were designed for the first time and used as carriers for the sustained release of the hydrophobic drug curcumin (Cur). These BAB-type triblock copolymers were synthesized via one-step enzymatic polycondensation with catalysis by immobilized lipase B from Candida antarctica (CALB). The copolymers could self-assemble to form flower-like nanosized micelles in aqueous solution. The pH-triggered disassembly behaviors of the micelles were evaluated from the changes of the micellar size and molecular weight due to the acid-degradable β-thiopropionate groups in the hydrophobic PTE core. Cur was encapsulated into the micelles and showed faster release at pH 5.0 than pH 7.4. In vitro experiments indicated that the copolymers were non-cytotoxic, while the Cur-loaded micelles effectively inhibited the proliferation of HeLa cells. All these findings demonstrated the potential of PTE-b-PEG-b-PTE triblock copolymers as a promising pH-responsive nanocarrier for controlled drug delivery.

Graphical Abstract

Keywords:

• Enzymatic polymerization
• pH-responsive micelles
• poly(β-thioether ester)
• self-assembly

Acknowledgments

We would like to thank the Comprehensive Training Platform of Specialized Laboratory, College of Chemistry, Sichuan University for DLS analysis.

Additional information

Funding

This work was financially supported by the Chengdu University New Faculty Start-up Fund in China (2081916042), National Program on Key Basic Research Project of China (973 Program, 2012CB720603 and 2013CB328900), and the National Science Foundation of China (No. 21232005).