Work

Multifunctional saikosaponin D-liposomes for hepatocellular carcinoma: Formulation optimization, characterization, and in vitro/in vivo evaluation

Year: 2025

Type: article

Abstract: The study aimed to construct saikosaponin D (SSD)-based liposomes modified with phosphatidic acid (PA) and poloxamer 407 (P407) (termed P407-SSD-Lps), and to evaluate their tumor-targeting ability and antitumor efficacy through in vitro and in vivo experiments. The preparation process and formulation of the P407-SSD-Lps were optimized using single-factor and orthogonal experimental designs, followed by systematic characterization. Their antitumor activity and targeting specificity were assessed through in vitro experiments. Additionally, the tumor-targeting capability, therapeutic efficacy, and biocompatibility of the P407-SSD-Lps were investigated in murine orthotopic hepatocellular carcinoma transplantation models. The P407-SSD-Lps optimized through single-factor and orthogonal experiments exhibited ideal physicochemical properties. In vitro results demonstrated that the P407-SSD-Lps enhanced cell membrane permeability and promoted cellular uptake in the HepG2 cells. Additionally, they significantly inhibited the HepG2 cells proliferation and induced apoptosis. In murine orthotopic hepatocellular carcinoma transplantation models, the P407-SSD-Lps exhibited prolonged tumor accumulation and demonstrated potent antitumor efficacy with favorable biocompatibility. When delivering doxorubicin (DOX), the system not only retained high biocompatibility but also exhibited enhanced therapeutic efficacy. Employing the SSD as both a liposomal membrane stabilizer and a therapeutic agent constituted a novel expansion of “drug-excipient integration” material applications. Moreover, the SSD-based P407-SSD-Lps system functioned as a stable and efficient multifunctional liposomal delivery system, offering innovative therapeutic avenues for hepatocellular carcinoma treatment. • Developed SSD-based liposomes implementing a “drug-excipient integration” strategy: SSD dually functions as structural stabilizer (cholesterol replacement) and therapeutic agent for HCC treatment. • Engineered cholesterol-free P407-SSD-Lps using SSD, adding inherent antitumor activity of SSD. • Optimized PA/P407-modified P407-SSD-Lps demonstrated improved stability, prolonged circulation, enhanced biocompatibility, and superior hepatocyte-specific targeting. • Designed P407-SSD-Lps significantly enhanced HepG2 cellular uptake, inhibited proliferation, induced apoptosis, and showed potent antitumor efficacy in orthotopic HCC mouse models. • Established as stable multifunctional delivery system, then co-delivering DOX with enhanced efficacy and maintained biocompatibility for HCC therapy in vivo.

Source: International Journal of Pharmaceutics X

DOI: 10.1016/j.ijpx.2025.100445