nab-Paclitaxel mechanisms of action and delivery

J Control Release. 2013 Sep 28;170(3):365-72. doi: 10.1016/j.jconrel.2013.05.041. Epub 2013 Jun 11.

Abstract

Taxanes are a key chemotherapy component for several malignancies, including metastatic breast cancer (MBC), ovarian cancer, and advanced non-small cell lung cancer (NSCLC). Despite the clinical benefit achieved with solvent-based (sb) taxanes, these agents can be associated with significant and severe toxicities. Albumin-bound paclitaxel (Abraxane; nab®-Paclitaxel), a novel solvent-free taxane, has demonstrated higher response rates and improved tolerability when compared with solvent-based formulations in patients with advanced MBC and NSCLC. The technology used to create nab-paclitaxel utilizes albumin to deliver paclitaxel, resulting in an advantageous pharmacokinetic (PK) profile. This review discusses the proposed mechanism of delivery of nab-paclitaxel, including an examination into a hypothesized greater ability to leverage albumin-based transport relative to sb-paclitaxel. An advantageous PK profile and the more efficient use of albumin-based transport may contribute to the preclinical finding that nab-paclitaxel achieves a 33% higher tumor uptake relative to sb-paclitaxel. Another possible contributing factor to the tumor accumulation of nab-paclitaxel is the binding of albumin to secreted protein acidic and rich in cysteine (SPARC), although the data supporting this relationship between SPARC and nab-paclitaxel remain largely correlative at this point. Recent data also suggest that nab-paclitaxel may enhance tumor accumulation of gemcitabine in pancreatic cancer treated with both agents. Additionally, a possible mechanistic synergy between nab-paclitaxel and capecitabine has been cited as the rationale to combine the two agents for MBC treatment. Thus, nab-paclitaxel appears to interact with tumors in a number of interesting, but not fully understood, ways. Continued preclinical and clinical research across a range of tumor types is warranted to answer the questions that remain on the mechanisms of delivery and antitumor activity of nab-paclitaxel.

Keywords: Cancer; Mechanism of action; Mechanism of delivery; Taxane; nab-Paclitaxel.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Albumins / administration & dosage*
  • Albumins / chemistry
  • Albumins / pharmacokinetics
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacokinetics

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Antineoplastic Agents, Phytogenic
  • Paclitaxel