Design and evaluation of curcumin-loaded poloxamer hydrogels as injectable depot formulations
Ashok David Jose, Kea Leigh Foo, Grace Hu, Linda Ngar, Bovinae Ryda, Jagdish K. Jaiswal, Zimei Wu, Priyanka Agarwal, Sachin Thakur
Abstract
Poloxamer hydrogels are of interest as injectable depot delivery systems. However, their use for delivering hydrophobic drugs, such as curcumin, is limited due to poor loading capacity. Here, we evaluated the influence of incorporating hydrophobic medium chain triglycerides (MCT) or amphiphilic polyethylene glycol 400 (PEG400) on the physicochemical properties, drug loading, and in vitro compatibility of a curcumin-loaded poloxamer hydrogel. Poloxamer 407 and 188 hydrogel formulations (16:6 w/w) were prepared and MCT and PEG400 (saturated with curcumin) were added to these systems, either alone or in combination, up to a 10 % w/w additive solvent load. Formulation viscoelasticity, gelation behaviour, injectability, morphology and release profiles were assessed. The cytocompatibility of the formulations was also assessed on dermal fibroblasts (HDFn). Both additives increased curcumin loading into the formulation. Addition of MCT to the hydrogel significantly increased its gelation speed, while PEG400 had a less profound impact. Both additive solvents increased the force required to inject the formulation. PEG400 containing systems were single phase, whereas MCT addition created emulsion systems. All formulations released ∼20-30 % of their loaded curcumin in a sustained fashion over 24 h. The modified hydrogel systems showed good biocompatibility on cells when administering up to ∼100-150 µM curcumin into the culture. This study addresses a key limitation in loading hydrophobic drugs into hydrogels and provides a strategy to enhance drug loading and performance of hydrogels by integrating additives such as MCT and PEG400 into the systems.