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oai:ebyu-rdlopen.rawdatalibrary.net:ebyu/124562026-10-18T21:13:18Zopenairedrivercom_ebyu_10000col_ebyu_10001

In vitro evaluation and in vivo efficacy studies of a liposomal doxorubicin-loaded glycyrretinic acid formulation for the treatment of hepatocellular carcinomaDiril, MineÖzdokur, Kemal VolkanYıldırım, YelizKarasulu, H. YeşimDoxorubicin hydrochlorideglycyrrhetinic acidhepatocellular carcinomaliver-targeted drugproliposomal drug delivery systemAnimalsCarcinoma, HepatocellularCell Line, TumorDoxorubicinDrug Delivery SystemsLiver NeoplasmsMicePolyethylene Glycolsmacrogolmacrogol 2000analytic methodanimal cellanimal experimentanimal modelanimal tissueArticlecalibrationcell membrane permeabilitycontrolled studycytotoxicitydifferential scanning calorimetrydispersitydrug formulationelectric resistanceencapsulationHepatocellular carcinoma (HCC), more than 800 000 cases reported annually, is the most common primary liver cancer globally. Doxorubicin hydrochloride (Dox-HCl) is a widely used chemotherapy drug for HCC, but efficacy and tolerability are limited, thus critical to develop delivery systems that can target Dox-HCl to the tumour site. In this study, liver-targeting ligand glycyrrhetinic acid (Gly) was conjugated to polyethylene glycol (PEG) via Steglich reaction and incorporated in liposomes, which were then loaded with Dox-HCl by pH gradient method. The optimal formulation Gly–Peg-Dox-ProLP-F6 showed high Dox-HCl encapsulation capacity (90.0%±1.85%), low particle size (120 ± 3.2 nm). Gly–Peg-Dox-ProLP-F6 formulation demonstrated substantially greater toxicity against HCC cells than commercial Dox-HCl formulation (greater against 1.14, 1.5, 1.24 fold against Hep G2, Mahlavu and Huh-7 cells, respectively), but was 1.86-fold less cytotoxic against non-cancerous cell line AML-12. It increased permeability from apical to basolateral (A–B) approximately 2-fold. Gly–Peg-Dox-ProLP-F6 demonstrated superior antitumor efficacy in mouse liver cancer model as evaluated by IVIS. Isolated mouse liver tissue contained 2.48-fold Dox more than Dox-HCl after administration of Gly–Peg-Dox-ProLP-F6, while accumulation in heart tissue was substantially lower. This Gly–Peg-Dox-ProLP-F6 formulation may improve HCC outcomes through superior liver targeting for enhanced tumour toxicity with lower systemic toxicity. © 2023 Informa UK Limited, trading as Taylor & Francis Group.Taylor and Francis Ltd.2023Articlehttps://rdlopen.rawdatalibrary.net/r/ebyu/12456https://doi.org/10.1080/10837450.2023.22743941083-7450enPharmaceutical Development and Technologyinfo:eu-repo/semantics/openAccessinfo:eu-repo/semantics/articlehttps://ebyu-rdlopen.rawdatalibrary.net/tr/items/ebyu/12456