Targeted surface engineered magnetic nanoformulation for hepatocellular carcinoma: A preclinical approach to improve in vivo safety and bioavailability

초록

Liver cancer, primarily hepatocellular carcinoma (HCC) is an aggressive cancer with wide spread globally. Lenvatinib (LEN) is a selective first line medication for HCC therapy. However, its clinical effectiveness is hampered by poor solubility, suboptimal pharmacokinetics, low bioavailability and severe side effects that frequently weaken its efficiency. To counter these aforementioned problems, we reported the development of pluronic F127 decorated citric acid capped LEN-loaded porous magnetic nanoclusters (PF127/CA/LEN@pMNCs). The formulation was characterized with atomic force microscopy (AFM), energy dispersive X-ray spectroscopy (EDX), atomic absorption spectroscopy (AAS), Raman spectroscopy, proton (1H) and Carbon 13 (13C) nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS). Moreover, cumulative in vitro release and antitumor study against Huh 7 cells were performed followed by pharmacokinetic, biodistribution and in vivo safety investigations of the PF127/CA/LEN@pMNCs and its comparison with LEN-dispersion. PF127/CA/LEN@pMNCs were found to have quasi-spherical shape and nanometric size (<200 nm). The atomic percentage and weight percentage of carbon, nitrogen, oxygen and iron were respectively found as 35.0, 1.8, 35.6, 27.7 % and 16.4, 1.0, 22.2, 60.4 % and were distributed evenly throughout the PF127/CA/LEN@pMNCs with magnetite as the main core. Moreover, the spectra of 1H and 13C NMR confirmed the coexistence of all the three typical signal groups in PF127/CA/LEN@pMNCs, including PF127, CA and LEN. Additionally, the PF127/CA/LEN@pMNCs demonstrated sustained release of LEN (72% in 48 h) at pH 6.8 when compared with LEN-dispersion. Similarly, the cell viability of Huh 7 cells was reduced to 4.94% at 100 μg/mL concentration of PF127/CA/LEN@pMNCs in 24 h. Furthermore, PF127/CA/LEN@pMNCs demonstrated 3.8∼fold enhanced bioavailability, 3.7∼fold long circulation time and enhanced liver localization. It can be concluded that PF127/CA/LEN@pMNCs with sustained release, optimum antitumor activity, biodistribution, enhanced bioavailability, and in vivo safety profile may be a potential nanoplatform for HCC therapy. © 2026 Elsevier B.V.

키워드