Ammonium Sulfate Gradient-Prepared Anlotinib-Loaded Liposomes for Potent Tumor Therapy with Decreased Side Effect

Anlotinib, a multitargeted tyrosine kinase inhibitor (TKI) with a dual effect of inhibiting both tumor angiogenesis and tumor cell proliferation, holds great promise in cancer therapy. However, its clinical application has been limited due to off-target side effects. With the rapid development of drug delivery systems, there is increasing potential to improve therapeutic efficacy while reducing the toxicity associated with free drugs. Among these, liposomes stand out due to their excellent biocompatibility, and several liposomal drug formulations have been approved by the U.S. Food and Drug Administration (FDA). In this study, we prepared anlotinib-loaded liposomes (designated as Lipo-Anlotinib) using the ammonium sulfate gradient method, aiming to enhance its clinical applicability through a more efficient delivery system. The antitumor activity of Lipo-Anlotinib was evaluated in vitro against three cell lines (A549, 4T1, and CT26). Additionally, Lipo-Anlotinib exhibited improved therapeutic efficacy over free anlotinib in a 4T1 subcutaneous tumor model. Serum biochemical analysis and histological examination revealed that Lipo-Anlotinib exhibited reduced toxicity in comparison to free anlotinib. This liposomal formulation offers a promising approach to enhancing the antitumor efficacy while mitigating the side effects of anlotinib.