Preparation of nano-sized multi-vesicular vesicles (MVVs) and its application in co-delivery of doxorubicin and curcumin.

Multi-vesicular vesicles (MVVs) offer structural advantages in terms of drug encapsulation and physiological stability. In this study, we address the challenge of preparing small-sized MVVs for drug delivery. The nano-sized MVVs (∼120 nm) loaded with doxorubicin (DOX) and curcumin (CUR) (DOX/CUR@MVVs) were successfully prepared using a glass bead combined with a thin film dispersion method. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis confirmed the independent non-homocentric vesicle structures of DOX/CUR@MVVs with homogeneous particle sizes. The experimental results showed high encapsulation rates of DOX and CUR in DOX/CUR@MVVs, reaching 82.5 ± 0.75 % and 85.9 ± 0.69 %, respectively. Moreover, the MVVs exhibited good biosafety and sustained release properties. Notably, the bioavailability of DOX and CUR in DOX/CUR@MVVs was enhanced compared to free DOX and CUR, with increases of 4.2 and 2.1 times, respectively. And the half-life of DOX and CUR was extended by 10 times in DOX/CUR@MVVs. In vivo antitumor experiments demonstrated that nano-sized DOX/CUR@MVVs significantly improved the antitumor activity while reducing the toxic side effects of DOX. Overall, the successful preparation of nano-sized DOX/CUR@MVVs and their potent and low-toxic antitumor effects provide a critical experimental reference for the combined antitumor therapy of MVVs and liposomes.