Shell-Cross-Linked Micelles from PNIPAM-b-(PLL)2 Y-Shaped Miktoarm Star Copolymer as Drug Carriers

Well-defined AB(2) Y-shaped miktoarm star copolymers of PNIPAM-b-(PZLL)(2) and PNIPAM-b-(PLL)(2) were synthesized through the combination of atom transfer radical polymerization (ATRP), ring-opening polymerization (ROP), and click chemistry, where PNIPAM, PZLL, and PLL arc poly(N-isopropylacrylamide), poly(epsilon-benzyloxycarbonyl-L-lysine), and poly(L-lysine), respectively. Propargyl amine was employed as ROP initiator for the preparation of alkynyl-terminated PZLL. Diazide-terminated PNIPAM was obtained with an azide-containing ATRP initiator. The subsequent click reaction led to the formation of PNIPAM-b-(PZLL)(2). After the removal of the benzyloxycarbonyl group, water-soluble PNIPAM-b-(PLL)(2) was obtained. The core shell micelles of PNIPAM-b-(PLL)(2) were formed above lower critical solution temperature of PNIPAM block. At this temperature, the shell cross-linking was performed through the reaction between glutaraldehyde and the primary amine groups of the PLL shell, affording the micelles with the endurance to temperature and pH changes. These shell-cross-linked micelles were used as drug nanocarriers and the release profile was dually controlled by the solution temperature and the cross-linking degree.