Chemoembolization agents
Inventors
Na, James • IMAGAWA, David • Tucci, Fabio • Beaton, Graham • RAVULA, Satheesh
Assignees
Bruin Biosciences Inc • University of California San Diego UCSD
Publication Number
US-12357570-B2
Publication Date
2025-07-15
Expiration Date
2038-05-25
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Abstract
Described herein is a chemoembolization therapy, which combines therapeutic effects of peripheral arterial occlusion with the local administration of an anti-cancer agent. A particle or microsphere occludes the arteries providing blood flow to the tumor, resulting in tumor oxygen deprivation. The anti-angiogenic agent is an anti-cancer drug, as described herein.
Core Innovation
The invention relates to chemoembolization therapy combining the therapeutic effects of peripheral arterial occlusion with the local administration of an anti-cancer agent. It involves particles or microspheres that occlude arteries supplying blood to tumors, causing tumor oxygen deprivation, alongside an anti-cancer agent delivered locally. This combination achieves a localized high concentration of the drug while minimizing systemic side effects.
The problem addressed is the limitation of current chemoembolization methods where therapeutic agents need to be positively charged and water-soluble to be loaded onto embolizing particles or microspheres, restricting the use of effective anti-cancer drugs that are weakly charged, uncharged, or poorly water soluble, such as Sorafenib. Existing embolization agents cannot efficiently load these effective drugs, limiting treatment to agents less efficacious against cancers like hepatocellular carcinoma (HCC).
The innovation disclosed includes chemoembolization agents comprising an embolizing particle or microsphere, an encapsulating agent (such as liposomes), and one or more therapeutic agents that are weakly charged, uncharged, or poorly water soluble. The encapsulating agent is affixed to the embolizing particle or microsphere through ionic or other non-covalent interactions and is configured to release the therapeutic agents. This enables loading of effective anti-cancer agents previously incompatible with embolizing particles, improving treatment options for solid vascularized tumors, including liver cancers.
Claims Coverage
The claims define inventive features focusing on a method of treating cancer using a chemoembolization agent with specific components and characteristics. The claims include multiple inventive features related to the structure and use of the chemoembolization agent, therapeutic agents, and methods of administration.
Method for administering chemoembolization agent
Administering to a subject a pharmaceutical composition comprising an embolizing particle or microsphere, an encapsulating agent affixed to it through ionic or non-covalent interactions, and one or more therapeutic agents within the encapsulating agent, each therapeutic agent being uncharged or weakly charged or poorly soluble at physiological pH, with the encapsulating agent configured to release the therapeutic agents.
Targeted arterial administration
Administering the effective amount of chemoembolization agent via catheter into an arterial blood vessel that vascularizes a solid tumor, specifically including the hepatic artery.
Cancer types treated
The method applies to liver cancer, particularly hepatocellular carcinoma.
Therapeutic dosing range
Administering the therapeutic agents at doses from about 0.01 mg/kg to about 10 mg/kg of body weight.
Charge characteristics of therapeutic agents
Use of therapeutic agents that are weakly negatively charged or weakly positively charged within the encapsulating agent.
Anti-cancer agents used
Therapeutic agents include anti-cancer drugs selected from Sorafenib, Regorafenib, Lenvatinib, Tirapazamine, Cabozantinib, or Sunitinib.
Combination with non-encapsulated therapeutic agents
Chemoembolization agents may further include non-encapsulated therapeutic agents affixed via a releasable mechanism to the embolizing particle or microsphere.
Material composition of embolizing particles
Embolizing particles or microspheres are made from polyvinyl alcohol materials or selected from beads of sulfonate functionalized polyvinyl alcohol hydrogels, acetalized polyvinyl alcohol hydrogels, hydrogel cores coated with poly bis[trifluoroethoxy]phosphazene, polyvinyl alcohol-co-sodium acrylate cross-linked hydrogels, and polyethylene glycol/3-sulfopropyl acrylate hydrogel networks.
Encapsulating agent characteristics
The encapsulating agent is a liposome, particularly a cationic liposome comprising a mixture of DOTAP and DOPC lipids.
Liposome composition ranges
The cationic liposome comprises a DOTAP to DOPC molar ratio ranging from 1:9 to 9:1.
The claims cover a method for treating cancer by administering a chemoembolization agent comprising an embolizing particle or microsphere and a liposome-based encapsulating agent carrying one or more weakly charged or poorly soluble therapeutic agents. The claims specify the material compositions, therapeutic combinations, dosing, targeted vascular delivery, and release mechanisms, aiming to enable effective local delivery of various anti-cancer drugs via chemoembolization.
Stated Advantages
Allows loading of weakly charged or uncharged and poorly water soluble anti-cancer drugs onto embolizing particles or microspheres to expand treatment options.
Achieves high local concentrations of therapeutic agents at tumor sites while minimizing systemic toxicity and side effects.
Enables use of clinically effective drugs like Sorafenib in chemoembolization, which was previously not feasible due to solubility and charge limitations.
Improves efficacy of chemoembolization by combining occlusion of blood supply with targeted drug delivery.
Documented Applications
Treatment of solid vascularized tumors including liver cancer, hepatocellular carcinoma, and kidney cancer using chemoembolization agents.
Use in intra-arterial administration, particularly into the hepatic artery for targeted delivery to liver tumors.
Combination therapies with surgery, chemotherapy, radiotherapy, and radioembolization beads for enhanced cancer treatment.
Use in transcatheter arterial chemoembolization (TACE) procedures to occlude tumor blood flow and deliver anti-cancer agents.
Use in animal tumor models, specifically rabbit VX2 liver tumor model, for evaluation of efficacy and pharmacokinetics.
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