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MRI visible drug eluting magnetic microspheres for transcatheter intra-arterial delivery to liver tumors.

ABSTRACT: Magnetic resonance imaging (MRI)-visible amonafide-eluting alginate microspheres were developed for targeted arterial-infusion chemotherapy. These alginate microspheres were synthesized using a highly efficient microfluidic gelation process. The microspheres included magnetic clusters formed by USPIO nanoparticles to permit MRI and a sustained drug-release profile. The biocompatibility, MR imaging properties and amonafide release kinetics of these microspheres were investigated during in vitro studies. A xenograft rodent model was used to demonstrate the feasibility to deliver these microspheres to liver tumors using hepatic transcatheter intra-arterial infusions and potential to visualize the intra-hepatic delivery of these microspheres to both liver tumor and normal tissues with MRI immediately after infusion. This approach offer the potential for catheter-directed drug delivery to liver tumors for reduced systemic toxicity and superior therapeutic outcomes.

SUBMITTER: Kim DH

PROVIDER: S-EPMC4350010 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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MRI visible drug eluting magnetic microspheres for transcatheter intra-arterial delivery to liver tumors.

Kim Dong-Hyun DH Chen Jeane J Omary Reed A RA Larson Andrew C AC

Theranostics 20150207 5

Magnetic resonance imaging (MRI)-visible amonafide-eluting alginate microspheres were developed for targeted arterial-infusion chemotherapy. These alginate microspheres were synthesized using a highly efficient microfluidic gelation process. The microspheres included magnetic clusters formed by USPIO nanoparticles to permit MRI and a sustained drug-release profile. The biocompatibility, MR imaging properties and amonafide release kinetics of these microspheres were investigated during in vitro s ...[more]

PMID: 25767615

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Project description:PurposeTo validate the therapeutic efficacy of sorafenib-eluting embolic microspheres (SOR-EMs) used in combination with transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC) in a preclinical animal model.Materials and methodsSOR-EMs were prepared with poly(d,l-lactide-co-glycolide), iron oxide nanoparticles, and sorafenib. The morphology of the prepared SOR-EMs was confirmed by using optical microscopy. Drug release from the SOR-EMs was quantified in vitro by using high-performance liquid chromatography. In an orthotopic rat model of HCC, embolic doxorubicin-Lipiodol (ethiodized oil) emulsion (DLE) and SOR-EMs were sequentially injected into the hepatic artery of the rats: The rats in group 1 were injected with DLE; group 2 was injected with DLE plus unloaded embolic microspheres (DLE + EM); group 3, with DLE plus SOR-EMs (DLE + SOR-EM); and group 4, with saline solution. The SOR-EM and tumor size changes in each group (of six rats each) over time were measured by using MRI. Tissues were assessed by using immunohistochemistry, with hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated dUTP (2'-deoxyuridine 5'-triphosphate) nick-end labeling staining used for dead cells and CD34 staining used for new microvessel formation.ResultsThe SOR-EMs were a mean size of 6.6 μm ± 2.3 (standard deviation) and showed 53.7% ± 8.3 sorafenib loading efficiency with T2-weighted MRI capability. In the HCC rat model, the intra-arterially injected SOR-EMs were successfully monitored by using MRI. The DLE + SOR-EM-treated rats showed a superior tumor growth-inhibitory effect compared with the rats treated with DLE only (P < .05). Immunohistochemical assessment of tissue specimens showed that compared with the other treatment groups, the DLE + SOR-EM treatment group had the lowest number of microvessels, as quantified by using the percentage of CD34-positive stained area (P < .01 for all comparisons).ConclusionIn a preclinical rat HCC model, SOR-EMs used in combination with DLE TACE were effective in treating HCC.Keywords: Chemoembolization, Experimental Investigations, Laboratory Tests, Liver, Technology Assessment Supplemental material is available for this article. © RSNA, 2021See also the commentary by Yamada and Gayed in this issue.

Dataset Information

MRI visible drug eluting magnetic microspheres for transcatheter intra-arterial delivery to liver tumors.

Publications

MRI visible drug eluting magnetic microspheres for transcatheter intra-arterial delivery to liver tumors.

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