Heat-induced solubilization of curcumin in kinetically stable pluronic P123 micelles and vesicles: An exploit of slow dynamics of the micellar restructuring processes in the aqueous pluronic system

Abstract

Wide therapeutic potential combined with low cost and negligible toxicity makes curcumin one of the most sought after drugs in recent times. Its poor aqueous solubility and low bioavailability are often overcome by using micelles and vesicles as its carriers. The substances that are commonly used for this purpose are a class of nonionic surfactants called pluronics. Solubilization of curcumin in aqueous systems of these surfactants is carried out by thin film hydration method presumably because slow dynamics of micellar restructuring processes in them creates hindrance for direct solubilization. In this manuscript, we show that this problem can be overcome and curcumin can be solubilized directly in pluronic P123 micellar solutions by heating them to the phase separation temperature in the presence of curcumin. The obtained curcumin containing micellar solutions show cytotoxicity on human breast carcinoma (MCF7) cells with IC50 values similar to that shown by free curcumin solution. Addition of mucoadhesive polymer κ-Carrageenan into these solutions converts them to curcumin containing gels and patches with rheological properties suitable for topical application. These solutions also exhibit systematic spherical-to-worm like micellar-to-vesicular structural transitions in the presence of NaCl. The large curcumin containing aggregates thus formed show kinetic stability with respect to dilution, which is an important attribute for drug delivery application. Characterization of the micellar and vesicular systems and gels were carried out by SANS, DLS and rheological measurements. The obtained results represent first systematic study on solubilization of curcumin in pluronic aggregates of various shapes and size.