Fabrication of pH- and Thermoresponsive Three-Layered Micelles via Host-Guest Interactions.

Abstract

Well-defined β-cyclodextrin (β-CD)-terminated double hydrophilic diblock copolymers (DHBCs), β-CD- poly(di(ethylene glycol) methyl ether methacrylate) (PMEO2 MA)-b-poly(2-(diethylamino)ethyl methacrylate) (PDEA) (BP1) and β-CD-PDEA-b-PMEO2 MA (BP2), are synthesized via sequential atom transfer radical polymerizations of di(ethylene glycol) methyl ether methacrylate and 2-(diethylamino)ethyl methacrylate using alkynyl-functionalized initiator, followed by click reactions with an excess of mono-azido-substituted β-cyclodextrin (β-CD-N3 ). The micellization behavior of these as-prepared DHBCs in aqueous solutions suffers from insufficient colloidal stabilities at basic pH and high temperatures (e.g., pH 9 and 45 °C), resulting in the formation of macroscopic precipitations. However, the stabilities of colloidal nanoparticles can be remarkably enhanced as a result of the convenient formation of three-layered micelles by taking advantage of host-guest interactions of BP1/BP2 and Ad-terminated poly(ethylene glycol). The pH- and thermoresponsive three-layered micelles with enhanced stability may augur promising applications in targeted drug delivery and controlled intelligent release.