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

Herein the synthesis of core cross‐linked (CCL) mixed micelles through a UV‐promoted thiol–ene 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 lipid‐ b ‐poly(acrylic acid) (lipid‐ b ‐PAA) only and then a mixture of pH‐sensitive lipid‐ b ‐PAA and thermo‐sensitive lipid‐ block ‐poly(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 °C) are simultaneously activated.