Thermoresponsive 2-hydroxy-3-isopropoxypropyl hydroxyethyl cellulose with tunable LCST for drug delivery

Thermoresponsive polymer 2-hydroxy-3-isopropoxypropyl hydroxyethyl celluloses (HIPECs) were successfully synthesized, characterized, and applied for thermoresponsive drug delivery. The lower critical solution temperature (LCST) of HIPEC could be easily tuned from 21.1 to 56.1 °C as the molar substitution (MS) increased from 1.21 to 2.88. Dynamic light scattering and transmission electron microscopy experiments revealed that HIPEC can self-assemble into nano-sized aggregates, and their size could be changed by variation in temperature. Additionally, the critical aggregation concentration (CAC) ranged from 0.101 to 0.805 g L^-1 by changing MS of HIPEC. In vitro drug delivery studies indicated that the amphotericin B (AmpB) release rate was much faster at temperatures above LCST; approximately 95% of the drug was released from aggregates in 40 h. MTT assays were conducted to evaluate the cytotoxicity of HIPEC, and the observation of the Hoechst 33342 living cell stain using confocal laser scanning microscopy confirmed the high cell viability as HIPECs were used.