Protein nanoparticles as drug carriers in clinical medicine

Abstract

Solvent-based delivery vehicles for chemotherapy agents have been instrumental in providing a means for hydrophobic agents to be administered intravenously. These solvents, however, have been associated with serious and dose-limiting toxicities. Solvent-based formulations of taxanes, a highly active class of cytotoxic agents, are associated with hypersensitivity reactions, neutropenia, and neuropathy. Nanoparticle technology utilizing the human protein albumin exploits natural pathways to selectively deliver larger amounts of drug to tumors while avoiding some of the toxicities of solvent-based formulations. 130 nM albumin-bound (nab) paclitaxel (nab-paclitaxel; Abraxane) was recently approved for use in patients with metastatic breast cancer who have failed combination therapy. In a randomized, phase III study in metastatic breast cancer, nab-paclitaxel was found to have improved efficacy and safety compared with conventional, solvent-based paclitaxel. Preliminary data also suggest roles for nab-paclitaxel as a single agent and in combination therapy for first-line treatment of metastatic breast cancer as well as in other solid tumors, including non-small-cell lung cancer, ovarian cancer, and malignant melanoma. The nab technology promises to have broad utility in cancer therapy, and clinical trials are underway using nab formulations of other water-insoluble anticancer agents such as docetaxel and rapamycin.