Synthesis of Dual-Sensitive Core Cross-Linked Mixed Micelles through Thiol-Ene Addition and Subsequent Drug Release Behavior

摘要

Herein the synthesis of core cross-linked (CCL) mixed micelles through a UV-promoted thiolene addition onto lipid core unsaturations and the subsequent release of an encapsulated drug depending on the external conditions (pH/temperature) are reported. The thiol-ene addition proceeds even in the absence of a photoinitiator to reach a complete conversion in a few minutes in bulk. The cross-linking reaction is applied in aqueous media onto lipidb-poly(acrylic acid) (lipid-b-PAA) only and then a mixture of pH-sensitive lipid-b-PAA and thermo-sensitive lipid-blockpoly( 2-isopropyl-2-oxazoline) copolymers. Structurally CCL micelles, preserved in any conditions, with a stimuli-sensitive corona whose swelling depends on the external pH or/and temperature, are successfully prepared. The release of vitamin K1 (VK1) is then investigated from all the previous systems and demonstrates a strong dependency to the external conditions. Indeed, the dual-sensitive CCL micelles release VK1 only when two triggers (pH 10 and T = 38 degrees C) are simultaneously activated.