Effect of curcumin and cosolvents on the micellization of Pluronic F127 in aqueous solution

The drug solubilization capacity of poloxamers like Pluronic F127 (PF127, poloxamer 407) is dependent on the physical form of the polymer; i.e. the distribution between unimers, aggregates, and micelles. Further, the formation of micelles can alter the stability and pharmacological activity of a drug molecule. It is therefore important to understand how the micellization process is influenced by the addition of excipients and drug molecules. Curcumin is considered a photosensitizer in antimicrobial photodynamic therapy (aPDT). The aPDT effect is optimized at a poloxamer concentration just below the critical micellar concentration (CMC). We aimed to evaluate the effect of curcumin in the presence of 1% ethanol (EtOH) or dimethyl sulfoxide (DMSO) on PF127 micellization. These organic solvents are commonly used in topical preparations as a cosolvent or penetration enhancer (in the case of DMSO). The micellization process was investigated by UV-vis spectroscopy, dynamic light scattering (DLS), and differential scanning calorimetry (DSC). The micellization process of PF127 was slightly influenced by the addition of 1% EtOH or DMSO; however, the presence of 20 μM curcumin enhanced the effect. Micellization was favored in PBS compared to MilliQ water. Structures were formed between PF127 and curcumin at poloxamer concentrations ≥0.3 μM which facilitated solubilization of the photosensitizer. The optimal PF127 concentration required to solubilize 20 μM curcumin but avoid micellization was in the range 0.3 μM-0.04 mM in PBS in the presence of 1 % EtOH or DMSO. A careful consideration of the curcumin, cosolvents, and PF127 concentrations is required to enhance the curcumin solubility and prevent the PF127 micellization.