Next generation strategy for tuning the thermoresponsive properties of micellar and hydrogel drug delivery vehicles using ionic liquids

Abstract

Amongst the greatest challenges in developing injectable controlled thermoresponsive micellar and hydrogel drug delivery vehicles include tuning the cloud point (CP) and reducing the gelation temperature (T_gel), below 37 °C, without compromising stability and solubility. Here, a unique strategy is employed using ionic liquid (IL) matrices to produce stable micellar and hydrogel delivery vehicles of distinct thermoresponsive properties. Each formulation includes the in-house synthesised polymer OEGMA300₂₀-b-BuMA₂₂-b-DEGMA₁₁ with FITC-IgG. Both micellar-IL and hydrogel-IL formulations exhibit enhanced stability following 120 days of storage under 4 °C compared to in phosphate buffered saline (PBS). Visual tests demonstrate that the CP of the micellar-IL carriers can be finely tuned (31–46 °C). Rheology measurements show that hydrogel strength is significantly increased and T_gel is reduced from 40 °C in PBS to 30 °C with IL. Finally, a unique stabilisation mechanism is proposed, triggered by the synergetic action of the excipients and IL in each system.