Rational design and analytical characterization of self-assembling poly(N‑isopropylacrylamide) and poly(2‑alkyl‑2‑oxazoline) hyaluronic acid copolymers

Abstract

In this study, we applied a systematic approach to establish an iterative workflow and to drive the chemical design of thermosensitive, in situ forming injectables as a function of the intended target product profile. Self-assembly, mechanical properties, physical state, and thermal transition behavior were assessed via nuclear magnetic resonance, oscillatory rheology, turbidimetry and visual inspection techniques. Thus, poly(N-isopropylacrylamide) (PNIPAM) and poly(2-alkyl-2-oxazoline)s (PAOx)s with LCSTs below body temperature were studied before and after grafting them onto azido-substituted hyaluronic acid (HA) via strain-promoted azide-alkyne cycloaddition (SPAAC). Ultimately, we identified critical material attributes able to guide the pharmaceutical development of in situ gelling thermosensitive polymers.

Keywords: Copper-free click chemistry; Hyaluronic acid; In situ forming DDS; Poly(2-alkyl-2-oxazoline)s; Thermosensitive polymers; poly(N-isopropylacrylamide).