ORGN 69 |
| Nanoparticle albumin bound (nab) technology is a platform that converts insoluble drugs into injectable nanoparticle form using human albumin. Nab-paclitaxel (Abraxane, ABI-007), the first nab-technology based drug approved, eliminates the need to use toxic solvents including Cremophor to formulate paclitaxel. Currently, other drugs based on nab-technology platform are under development, including ABI-008 (nab-docetaxel) and ABI-009 (nab-rapamycin). Nab technology enhances tumor penetration of a drug through albumin receptor (gp60)-mediated endothelial transcytosis and improves drug accumulation in tumor via binding to SPARC (Secreted Protein, Acidic and Rich in Cysteine), an albumin-binding protein overexpressed in majority of cancers. In tumor xenografts, nab-paclitaxel showed increased antitumor activity, enhanced endothelial cell transport and 33% higher intratumor paclitaxel concentration compared with equal dose of solvent-based paclitaxel (Taxol). SPARC plays important roles in tumor targeting by nab-technology based drugs, and high expression levels of SPARC correlated with enhanced response to nab-paclitaxel in tumor xenografts and head and neck cancer patients. In a Phase III clinical study in patients with metastatic breast cancer, nab-paclitaxel displayed great antitumor efficacy and a favorable safety profile versus Taxol. In a randomized Phase II study of first-line metastatic breast cancer patients, nab-paclitaxel displayed greater antitumor activity, improved progression free survival and improved safety when compared with docetaxel (Taxotere). In summary, nab-technology enhances the delivery and tumor targeting of hydrophobic drugs and provides substantial clinical advantages over conventional therapies. |
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New Molecular Strategies for Tumor-Targeting Drug Delivery
1:25 PM-5:20 PM, Sunday, August 19, 2007 BCEC -- 253 A/B/C, Oral
Division of Organic Chemistry |