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Title: Evaluation of the effect of SMA-pirarubicin micelles on colorectal cancer liver metastases and of hyperbaric oxygen in CBA mice.
Austin Authors: Daruwalla, Jurstine;Greish, Khaled;Nikfarjam, Mehrdad ;Millar, Ian;Malcontenti-Wilson, Caterina;Iyer, Arun K;Christophi, Christopher 
Affiliation: Department of Surgery, Austin Health Hospital, University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: 9-Aug-2007
Publication information: Journal of Drug Targeting; 15(7-8): 487-95
Abstract: Tetrahydropyranyladriamycin (THP or pirarubicin) destroys tumors via several mechanisms; one of which involves the production of ROS that requires molecular oxygen for its generation. SMA forms stable self-assembled associated micelles with pirarubicin (SMA-pirarubicin), and confers macromolecular characteristics to pirarubicin. This micellar macromolecular drug is selectively delivered to solid tumors via the EPR effect and its preferential tumor accumulation suppresses the systemic toxicity whilst its prolonged high concentration at the site of tumor enhances its efficacy much higher compared to free pirarubicin. Administration of SMA-pirarubicin micelle under HBO can further enhance the delivery of molecular oxygen that facilitates tumor selective generation of ROS, thus augmenting its antitumor potency. In this study, we evaluated the efficacy of SMA-pirarubicin micelles either as single drug or in combination with HBO in a mouse metastatic colorectal cancer model. At or below the maximum tolerated dose, SMA-pirarubicin remarkably reduced metastatic tumor nodules and it was far more effective than free pirarubicin. The data also suggests a potential benefit of combined therapy of HBO with micellar anthracyclins.
Gov't Doc #: 17671895
DOI: 10.1080/10611860701499839
Type: Journal Article
Subjects: Animals
Antineoplastic Agents.administration & dosage.adverse effects
Colorectal Neoplasms.pathology
Combined Modality Therapy
Disease Models, Animal
Dose-Response Relationship, Drug
Doxorubicin.administration & dosage.adverse effects.analogs & derivatives
Drug Delivery Systems
Hyperbaric Oxygenation
Liver Neoplasms.secondary.therapy
Mice, Inbred CBA
Microscopy, Electron, Scanning
Reactive Oxygen Species.metabolism
Appears in Collections:Journal articles

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