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.
Keywords: Cosolvents; Critical micellar concentration; Curcumin; Poloxamer.
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.