Amphiphile-drug interplay: Enhanced solubility and drug-tailored self-assembly for delivery applications

During the last three decades, the design of refined nanosized drug delivery systems employed peculiar temperature-responsive synthetic copolymers, Pluronics, capable to mimic biological systems. Biocompatibility and biodegradability, along with the possibility of opportunely tailoring the desired features of these macromolecules, can be exploited to develop carriers able to improve the solubility and the bioavailability of hydrophobic drugs. As passive agents, Pluronics have a high drug loading capacity in water and low immunogenicity, but they can also play a more active role by reacting to temperature changes. Within specific ranges of concentration, Pluronic aqueous solutions can be injected in liquid form and become soft solids at body temperature, allowing to modulate the drug release. The presence of additives can modify the thermal response of Pluronic molecules in water, possibly sensitizing the system to other stimuli (e.g., pH). In this work, the addition of hydrophobic Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) – ibuprofen (IBU), ibuprofen sodium salt (IBUNa), diclofenac potassium (DK) – in a 45 wt% Pluronic F68 aqueous solution was investigated by rheology, Differential Scanning Calorimetry (DSC), surface tension and wettability measurements. Pluronic F68 significantly increased the solubility of the drug in water. The thermo-reversible, self-assembling process was followed and phase transitions were identified through rheological oscillatory and steady measurements and calorimetric evaluations at different drug concentrations and temperatures. The effect of pH was also discussed by varying the drug type and its concentration. Lastly, empirical phase diagrams for the drug/Pluronic aqueous solutions were built.