Improving the Stability of Liposomal Curcumin by Adjusting the Inner Aqueous Chamber pH of Liposomes

[Image: see text] Curcumin (CURC) is a hydrophobic molecule and its water solubility can be greatly improved by liposome encapsulation. However, investigations on the stability of pH-sensitive molecules incorporated into liposomal membranes are limited. In this study, CURC-loaded liposomes with varied internal pH values (pH 2.5, 5.0, or 7.4) were prepared and designated as CURC-LP (pH 2.5), CURC-LP (pH 5.0), and CURC-LP (pH 7.4). Physical properties including particle size, ζ-potential, morphology, entrapment efficiency, and physical stabilities of these CURC-LPs were assessed. In addition, the chemical stability of liposomal CURC to different external physiological environments and internal microenvironmental pH levels were investigated. We found that among these CURC-LPs, CURU-LP (pH 2.5) has the highest entrapment efficiency (73.7%), the best physical stabilities, and the slowest release rate in vitro. Liposomal CURC remains more stable in an acid external environment. In the physiological environment, the chemical stability of liposomal CURC is microenvironmental pH-dependent. In conclusion, we prove that the stability of liposomal CURC is external physiological environment- and internal microenvironmental pH-dependent. These findings suggest that creating an acidic microenvironment in the internal chamber of liposomes is beneficial to the stability of liposomal CURC, as well as for other pH-sensitive molecules.