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Hyaluronic acid/doxorubicin nanoassembly-releasing microspheres for the transarterial chemoembolization of a liver tumor.

ABSTRACT: Doxorubicin (DOX)-loaded, hyaluronic acid-ceramide (HACE) nanoassembly-releasing poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) were developed for transarterial chemoembolization (TACE) therapy of liver cancer. DOX/HACE MSs with a mean diameter of 27??m and a spherical shape were prepared based on the modified emulsification method. Their in vitro biodegradability in artificial biological fluids was observed. A more sustained drug release pattern was observed from DOX/HACE MS than from DOX MS at pH 7.4. The cellular internalization efficiency of DOX of the DOX/HACE MS group was higher than that of the DOX MS group in liver cancer cells (HepG2 and McA-RH7777 cells), mainly due to CD44 receptor-mediated endocytosis of the released DOX/HACE nanoassembly. In both HepG2 and McA-RH7777 cells, the antiproliferation and apoptotic potentials of the DOX/HACE MS were significantly higher than those of the DOX MS (p?

SUBMITTER: Lee SY

PROVIDER: S-EPMC6058484 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Hyaluronic acid/doxorubicin nanoassembly-releasing microspheres for the transarterial chemoembolization of a liver tumor.

Lee Song Yi SY Choi Jin Woo JW Lee Jae-Young JY Kim Dae-Duk DD Kim Hyo-Cheol HC Cho Hyun-Jong HJ

Drug delivery 20181101 1

Doxorubicin (DOX)-loaded, hyaluronic acid-ceramide (HACE) nanoassembly-releasing poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) were developed for transarterial chemoembolization (TACE) therapy of liver cancer. DOX/HACE MSs with a mean diameter of 27 μm and a spherical shape were prepared based on the modified emulsification method. Their in vitro biodegradability in artificial biological fluids was observed. A more sustained drug release pattern was observed from DOX/HACE MS than from ...[more]

PMID: 29909706

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Project description:BACKGROUND:Liver cancer is the fifth most common cancer and the second cause of cancer-related deaths worldwide. Transarterial chemoembolization (TACE) is the best treatment of intermediate hepatocellular carcinoma (HCC). Doxorubicin is the most commonly used drug despite a low level of evidence. AIM:To compare the objective response rate of idarubicin-based TACE (Ida-TACE) against doxorubicin-based TACE (Dox-TACE) in intermediate stage HCC. METHODS:Between January 2012 and December 2014, all patients treated with TACE at our academic hospital were screened. Inclusion criteria were patients with Child-Pugh score A or B, a performance status below or equal to 1, and no prior TACE. Either lipiodol TACE or drug-eluting beads TACE could be performed with 10 mg of idarubicin or 50 mg of doxorubicin. Each patient treated with idarubicin was matched with two doxorubicin-treated patients. The TACE response was assessed by independent radiologists according to the mRECIST criteria. RESULTS:Sixty patients were treated with doxorubicin and thirty with idarubicin. There were 93% and 87% of cirrhotic patients and 87% and 70% of Child-Pugh A in the doxorubicin and idarubicin groups, respectively. The median number of HCC per patient was two in both groups with 31% and 26% of single nodules in doxorubicin and idarubicin groups, respectively. Objective response rate after first TACE was 76.7% and 73.3% (P = 0.797) with 41.7% and 40.0% complete response in doxorubicin and idarubicin groups, respectively. Progression-free survival was 7.7 mo in both groups, and liver transplant-free survival was 24.9 mo and 21.9 mo in doxorubicin and idarubicin groups, respectively. Safety profiles were similar in both groups, with grade 3-4 adverse events in 35% of Dox-TACE and 43% of Ida-TACEs. CONCLUSION:Ida-TACE and Dox-TACE showed comparable results in terms of efficacy and safety. Ida-TACE may represent an interesting alternative to Dox-TACE in the management of patients with intermediate stage HCC.

Project description:BackgroundDrug-eluting embolic transarterial chemoembolization (DEE-TACE) is an advance in TACE technique. However, at present there is insufficient evidence to support that DEE-TACE is superior to conventional TACE (cTACE) for hepatocellular carcinoma (HCC). The aim of this meta-analysis is to evaluate the efficacy and safety of TACE with CalliSpheres® microspheres (CSM-TACE) compared with cTACE in patients with HCC.Data sourcesPubMed, Embase, Web of Science, CNKI and Wanfang Databases were searched to identify relevant articles published before March 26, 2020. The data regarding treatment response, survival profile, adverse events and liver function indexes were retrieved.ResultsA total of 16 studies with 1454 HCC patients (722 treated with CSM-TACE and 732 with cTACE) were included. Patients receiving CSM-TACE had higher 1-month complete response (CR), objective response rate (ORR), disease control rate (DCR) (odds ratio (OR): 2.00, 95% confidence interval (95% CI): 1.29-3.09; OR: 2.87, 95% CI: 2.15-3.83; OR: 2.01, 95% CI: 1.37-2.95, respectively), 3-month CR, ORR, DCR (OR: 4.04, 95%CI: 2.46-6.64; OR: 3.39, 95%CI: 2.45-4.70; OR: 1.71, 95%CI: 1.14-2.55 respectively), and 6-month CR, ORR, DCR (OR: 4.02, 95%CI: 2.26-7.16; OR: 3.00, 95%CI: 2.05-4.38; OR: 2.66, 95%CI: 1.70-4.16 respectively) than those treated with cTACE. Furthermore, CSM-TACE exhibited a trend toward improved progression free survival (hazard ratio (HR): 0.86, 95%CI: 0.67-1.11) and overall survival (HR: 0.79, 95%CI: 0.59-1.07) over cTACE although these differences did not reach statistical significance. In terms of safety, the two TACE treatments showed similar post-treatment pain (OR: 0.84, 95%CI: 0.55-1.28), fever (OR: 0.99, 95%CI: 0.60-1.63), nausea/vomiting (OR: 0.84, 95% CI: 0.60-1.17), as well as 1-month follow-up alanine aminotransferase (Mean difference (MD): -3.66, 95%CI: -10.38-3.07), aspartate aminotransferase (MD: -2.30, 95%CI: -8.91-4.31) and total bilirubin (MD: -0.15, 95%CI: -2.26-1.96).ConclusionCSM-TACE displays superior treatment response, non-inferior survival profile and safety over cTACE in HCC patients.

Project description:Colorectal cancer is the third most frequently diagnosed cancer and the third leading cause of cancer related deaths in Taiwan. Of the 10,248 new colorectal patients diagnosed each year approximately 60% will develop liver metastasis during the course of their disease. In approximately 30% of these patients who develop liver metastasis the metastatic disease will remain confined to the liver. For the 70-75% of colorectal patients with colorectal liver metastasis not suitable for hepatic resection or similarly ablative therapy with curative intent, systemic chemotherapy is the standard initial management. However, after a patient has failed first- line and in some cases second-line chemotherapy, response rates fall to as low as 12% (Chen HX 2006). Transarterial chemoembolization (TACE) with microsphere is an alternative treatment because normal liver tissue receives most of its blood supply from the portal vein, while colorectal liver metastases derive most of their flow from the hepatic artery. Several clinical trials have explored the feasibility and the efficacy of TACE with microsphere as a treatment for patients with colorectal liver metastasis. HepaSphere represents a novel drug delivery system for chemoembolization, which can add two benefits to embolization therapy. First, by ionically binding the doxorubicin throughout the microspheres, more drug can be delivered into the tumor, with less escape into peripheral circulation. Second, conformability to the architecture of the vessel lumen, providing more contact surface area with the embolic material and the vessel intima, leading to a more complete occlusion. However, there are limited experiences in using HepaSphere TACE for colorectal liver metastasis in Taiwan. In this pilot study, we will evaluate the initiate safety and efficacy of Hepasphere microspheres loaded with a chemotherapeutic agent doxorubicin for the treatment of patients who have failed first-line and second-line systemic chemotherapy.

Dataset Information

Hyaluronic acid/doxorubicin nanoassembly-releasing microspheres for the transarterial chemoembolization of a liver tumor.

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Hyaluronic acid/doxorubicin nanoassembly-releasing microspheres for the transarterial chemoembolization of a liver tumor.

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