Apigenin-loaded galactose tailored PLGA nanoparticles: A possible strategy for liver targeting to treat hepatocellular carcinoma
2021
Ganguly, Soumya | Dewanjee, Saikat | Sen, Ramkrishna | Chattopadhyay, Dipankar | Ganguly, Shantanu | Gaonkar, Raghuvir | Debnath, Mita Chatterjee
Hepatocellular carcinoma (HCC) is the most common hepatic malignancy worldwide. Recent reports focusing on the efficacy of apigenin-loaded nanoparticles (NPs) in combating the progress of HCC encouraged us to develop galactose-tailored PLGA NPs loaded with apigenin (API-GAL-NPs) for active liver targeting to treat HCC. Two kinds of apigenin NPs, such as apigenin-PLGA NPs (API-NPs) and API-GAL-NPs were fabricated and characterized by size, surface morphology, encapsulation efficacy, and in vitro drug release kinetics. In vitro assays were performed on HepG2 cells to check the cellular internalization, cytotoxic potential, and apoptotic potential of free apigenin (API), API-NPs, and API-GAL-NPs. In this stdy, API-GAL-NPs exhibited improved cellular internalization of API resulting in significantly high cytotoxic and apoptotic potentials to HepG2 cells over API and API-NPs. In in vivo studies, API-GAL-NPs exhibited a better protective effect against DEN-induced HCC in rats evidenced by the significant reduction of nodule formation, downregulation of matrix metalloproteinases (MMP-2 and MMP-9), and induction of apoptosis in the liver than API and API-NPs. Histopathological studies and scintigraphic imaging also confirmed that API-GAL-NPs treatment achieved better therapeutic efficacy against DEN-induced HCC in rats over API-NPs. In conclusion, API-GAL-NPs may serve as a potential therapeutic agent against HCC in the future by achieving improved liver targeting.
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