Amidation of methyl ester-functionalised poly(2-oxazoline)s as a powerful tool to create dual pH- and temperature-responsive polymers as potential drug delivery systems

• Published in: Polymer chemistry 2023-05, Vol.14 (17), p.234-244
• Main Authors: Leiske, Meike N, Singha, Ronak, Jana, Somdeb, De Geest, Bruno G, Hoogenboom, Richard
• Format: Article
• Language: English
• Subjects: Amines; Block copolymers; Drug delivery systems; Nanoparticles; Phase separation; Phase transitions; Photon correlation spectroscopy; Polymer chemistry; Polymers; Rhodamine; Temperature dependence
• ISSN: 1759-9954; 1759-9962
• DOI: 10.1039/d3py00050h

In the past two decades, thermoresponsive polymers based on tertiary amine groups have been studied extensively as a class of dual-responsive polymers. In particular, their temperature-dependent phase transition can be further modulated by the pH value of the environment, rendering them interesting for applications in the biomedical area. In this contribution, we report methyl-ester-functionalised poly(2-alkyl-2-oxazoline)s (PAOx) as a versatile platform for the synthesis of tertiary-amine-functionalised PAOx via straightforward post-polymerisation amidation. The resulting polymers were investigated regarding their stimuli-responsiveness to both, pH value and temperature by turbidimetry measurements. Dynamic light scattering further confirmed the formation of polymeric nanoparticles upon phase separation of block copolymers comprising a responsive polymer block and poly(2-methyl-2-oxazoline) as permanently hydrophilic block. Furthermore, a hydrophobic Rhodamine B derivative was used as model cargo and was found to induce the formation of stable nanoparticles in biological media beyond the responsiveness to pH and temperature of these polymers. Treatment of MDA-MB-231 breast cancer cells with such nanoparticles containing both, the Rhodamine B octadecyl-derivative and paclitaxel, suppressed their proliferation sufficiently in vitro . Altogether, PAOx with tertiary amines are presented as versatile materials with interesting characteristics and potential applications in the area of polymeric drug delivery. We present the synthesis of different amine-functionalised poly(2-oxazoline)s, their dual pH and temperature response as well as their capability to as promising stimuli responsive drug delivery vectors.