ArticleNaunyn-Schmiedeberg's archives of pharmacology2026
Preclinical evaluation of gefitinib and betulin-loaded surface functionalized liposomes for the treatment of hepatocellular carcinoma via asialoglycoprotein receptor targeting.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Hepatocellular carcinoma (HCC) is difficult to treat, and gefitinib (GEF) monotherapy may offer limited therapeutic benefits. Combination or multimodal approaches are often required to achieve therapeutic efficacy in such cases. Betulin (BET), a naturally occurring triterpene, is used in combination with GEF to enhance therapeutic efficacy against HCC, but its clinical translation is not possible due to poor bioavailability and lack of targeted delivery. Therefore, we developed non-targeted and lactoferrin (Lf) grafted targeted liposomes of GEF (GEF-Lipo and GEF-Lf-Lipo) and BET (BET-Lipo and BET-Lf-Lipo) by the ethanol injection method and subsequently characterized them. The vesicular size of GEF-Lipo, GEF-Lf-Lipo, BET-Lipo, and BET-Lf-Lipo was found to be 119.5 ± 6.5, 159.1 ± 16.4, 140.7 ± 16.4, and 181.6 ± 4.8 nm, respectively. Polydispersity index (PDI) of GEF-Lipo, GEF-Lf-Lipo, BET-Lipo, and BET-Lf-Lipo was found to be 0.329 ± 0.1, 0.371 ± 0.05, 0.33 ± 0.14, and 0.399 ± 0.030, respectively. Encapsulation efficiencies (EE%) of GEF-Lipo, GEF-Lf-Lipo, BET-Lipo, and BET-Lf-Lipo were found to be 84.7 ± 1.22%, 90.08 ± 1.73%, 91.4 ± 2.63%, and 93.21 ± 1.88%, respectively. Furthermore, the in vivo study has been performed to assess the effectiveness of mixtures of GEF-BET, GEF-BET-Lipo, and asialoglycoprotein receptor (ASGPR) targeted GEF-BET-Lf-Lipo. Physiological parameters and HCC biomarker AFP were quantified. AFP levels were significantly increased in the cancer control versus normal control (p < 0.0001) and were significantly reduced by treatment with pristine drugs, non-targeted liposomes, and targeted liposomes (p < 0.0001), supporting the therapeutic effects of the formulations. Morphological changes in liver tissue were evaluated through histopathological examination and scanning electron microscopy (SEM). Western blotting and immunohistochemistry (IHC) showed that both GEF-BET-Lipo and GEF-BET-Lf-Lipo treatments significantly reduced pSTAT3 expression and increased the levels of the apoptotic marker caspase-3. Overall, the findings support the enhanced antitumor potential of GEF-BET-Lf-Lipo against HCC in animals.
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