Leveraging topological reactivity of cellulose nanocrystals with allomorph II (CNC-II) to create temperature-sensitive systems for ibuprofen delivery.

Cellulose nanocrystals (CNCs) have garnered attention for their renewable and reactive nature, yet CNC allomorph II (CNC-II) remains underexplored compared to the extensively studied CNC-I. This study bridges this gap by introducing a two-step carboxylamine condensation strategy to conjugate poly(ethylene glycol) (PEG) onto CNC-II via ethylenediamine, leveraging the high topochemical reactivity of CNC-II. Utilizing bicarboxylate-capped PEG as a probe, quartz crystal microbalance with energy dissipation (QCM-D) assays revealed a significant reactivity increase of 16.99 % in PEG grafting for CNC-II compared to CNC-I. Furthermore, a temperature-responsive CNC-II conjugate (CF4-II) was synthesized by grafting the thermosensitive polymer F124 (a block copolymer composed of PEO and PPO segments), demonstrating its utility in stabilizing Pickering emulsions for the temperature-controlled release of ibuprofen. The results of the in vitro release of ibuprofen encapsulated in CF4-II emulsions show that the release rate is more than quadrupled as the temperature increased from 37 °C to 40 °C, indicating that it is a promising smart drug carrier for fever management. These findings not only underscore the potential of CNC-II as a superior substrate for topological chemical reactions but also pave the way for the development of advanced materials and nanodevices with enhanced functionality and responsiveness.