Synthesis and characterization of temperature-sensitive block-graft PNiPAAm-b-(PαN₃CL-g-alkyne) copolymers by ring-opening polymerization and click reaction

This study synthesized thermo-sensitive amphiphilic block-graft PNiPAAm-b-(PαN₃CL-g-alkyne) copolymers through ring-opening polymerization of α-chloro-ε-caprolactone (αClCL) with hydroxyl-terminated macroinitiator poly(N-isopropylacrylamide) (PNiPAAm), substituting pendent chlorides with sodium azide. This was then used to graft various kinds of terminal alkynes moieties by means of the copper-catalyzed Huisgen's 1,3-dipolar cycloaddition ("click" reaction). ¹H NMR, FTIR, and gel permeation chromatography (GPC) was used to characterize these copolymers. The solubility of the block-graft copolymers in aqueous media was investigated using turbidity measurement, revealing a lower critical solution temperature (LCST) in the polymers. These solutions showed reversible changes in optical properties: transparent below the LCST, and opaque above the LCST. The LCST values were dependant on the composition of the polymer. With critical micelle concentrations (CMCs) in the range of 2.04-9.77 mg L ^-1, the block copolymers formed micelles in the aqueous phase, owing to their amphiphilic characteristics. An increase in the length of hydrophobic segments or a decrease in the length of hydrophilic segments amphiphilic block-graft copolymers produced lower CMC values. The research verified the core-shell structure of micelles by ¹H NMR analyses in D ₂O. Transmission electron microscopy was used to analyze the morphology of the micelles, revealing a spherical structure. The average size of the micelles was in the range of 75-145 nm (blank), and 105-190 nm (with drug). High drug entrapment efficiency and drug loading content were observed in the drug micelles.