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.

Acidic pH-Triggered Drug-Eluting Nanocomposites for Magnetic Resonance Imaging-Monitored Intra-arterial Drug Delivery to Hepatocellular Carcinoma

“…MRI observation of sorafenib–pH-DENs deposition within the liver was later confirmed with histological staining of the tissue for iron with Prussian blue. 9,10 As shown in Figure 5b, strong blue signal was observed not only at the peripheral rim of the tumor (upper image) but also at the intratumor vessel (bottom image). These results indicate that sorafenib–pH-DENs were effectively localized to the targeted tumor regions, including the rim and inner tumor, via transcatheter IA liver-directed infusion.…”

Polymeric materials for embolic and chemoembolic applications

“…Although clinical response was not significant, the microspheres accomplished the goal of in vivo tracking. The small size of the MSs may have been a contributing factor, carrying less drug than would a 300–500 μm MS. Another set of MRI visible drug eluting MSs using alginate, an anionic polysaccharide has been developed[121]. Alginate is composed of two uronic acid monomers: (1–4)-linked β-L-guluronic and α-D-mannuronic acids, and the monomers are linked via glycosidic bonds.…”

Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer

“…[1–4] No systemic chemotherapy has proven to be effective in HCC patients, except for the oral multi-kinase inhibitor Sorafenib in advanced stage patients with good liver function. [5, 6] Transcatheter arterial chemoembolization (TACE) under image-guidance using X-ray angiography has been performed as the primary option for unresectable HCC with an advanced stage. TACE utilizes the preferential blood supply of HCC derived from the hepatic artery (~95%), thereby allowing local chemotherapy and embolization with minimal damage to the surrounding healthy parenchyma (primarily supplied via portal vein).…”

“…TACE utilizes the preferential blood supply of HCC derived from the hepatic artery (~95%), thereby allowing local chemotherapy and embolization with minimal damage to the surrounding healthy parenchyma (primarily supplied via portal vein). [6] Conventional TACE is performed with intra-arterial infusion of iodized oil mixed with chemotherapeutic agents such as Doxorubicin (Dox) or drug combinations such as Dox, cisplatin and mitomycin. [7] Lipiodol (Andre Guerbet, Aulnay-sous-Bois, France) is the iodized oil which has been most commonly used in TACE.…”