Synthesis of amphiphilic temperature-sensitive poly(N-isopropylacrylamide)-block-poly(tetramethylene carbonate) block copolymers and micellar characterization

Amphiphilic thermally sensitive poly(N-isopropylacrylamide)-block-poly(tetramethylene carbonate) block copolymers were synthesized by ring-opening polymerization of tetramethylene carbonate with hydroxyl-terminated poly(N-isopropylacrylamide) (PNiPAAm) as macro-initiator in the presence of stannous octoate as catalyst. The synthesis involved PNiPAAm bearing a single terminal hydroxyl group prepared by telomerization using 2-hydroxyethanethiol as a chain-transfer agent. The copolymers were characterized using ¹H NMR and Fourier transform infrared spectroscopy and gel permeation chromatography. Their solutions show reversible changes in optical properties: transparent below the lower critical solution temperature (LCST) and opaque above the LCST. The LCST depends on the polymer composition and the media. Owing to their amphiphilic characteristics, the block copolymers form micelles in the aqueous phase with critical micelle concentrations (CMCs) in the range 1.11-22.9 mg L^-1. Increasing the hydrophobic segment length or decreasing the hydrophilic segment length in the amphiphilic diblock copolymers produces lower CMCs. A core-shell structure of the micelles is evident from ¹H NMR analyses of the micelles in D₂O. Transmission electron microscopic analyses of micelle morphology show a spherical structure of both blank and drug-loaded micelles. The blank and drug-loaded micelles have an average size of less than 130 nm. Observations show high drug-entrapment efficiency and drug-loading content for the drug-loaded micelles. Poly(N-isopropylacrylamide)-block-poly(tetramethylene carbonate) (PNiPAAm-b-PTMC) copolymers show cumulative average micelle diameter changes in solution as a function of temperature. An increase in the length of PTMC blocks results in an increase in size and stability of the micelles.