Design and evaluation of curcumin-loaded poloxamer hydrogels as injectable depot formulations.

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 10 % w/w. 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 lowered its gelation temperature, while PEG400 had no notable impact. Both additives 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 sustained fashion over 24 h. The modified hydrogel systems showed great 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 into and performance of hydrogels by integrating additives, such as MCT and PEG400 into the systems.

A comprehensive update of micro- and nanobubbles as theranostics in oncology.

Advances in diagnostic and imaging capabilities have allowed cancers to be detected earlier and characterized more robustly. These strategies have recently branched into theranostics whereby contrast agents traditionally used for imaging have been co-loaded with therapeutics to simultaneously diagnose and treat cancers in a patient-specific manner. Microbubbles (MBs) and nanobubbles (NBs) are contrast agents which can be modulated to meet theranostic needs particularly in the realm of oncology. The current review focuses on ultrasound-responsive MB/NB platforms used as a theranostic tool in oncology. We discuss in detail the key parameters that influence the utility of MB/NB formulations and implications of such treatment modalities. Recent advances in composition strategies, latest works in the pre-clinical stages and multiple paradigm-shifting innovations in the field of MB/NB are discussed in-depth in this review. The clinical application of MB/NB is currently limited to diagnostic imaging. Surface chemistry modification strategies will help tune the formulations toward therapeutic applications. It is also anticipated that MB/NB will see increased use to deliver gas therapeutics. Scalability and stability considerations will be at the forefront as these particles get introduced into the clinical theranostic toolbox.