Nanoparticle Albumin Bound Paclitaxel in the Treatment of Human Cancer: Nanodelivery Reaches Prime-Time?

Nanoparticle albumin bound paclitaxel (nab-paclitaxel) represents the first nanotechnology-based drug in cancer treatment. We discuss the development of this innovative compound and report the recent changing-practice results in breast and pancreatic cancer. A ground-breaking finding is the demonstration that nab-paclitaxel can not only enhance the activity and reduce the toxicity of chromophore-diluted compound, but also exert activity in diseases considered refractory to taxane-based treatment. This is the first clinical demonstration of major activity of nanotechnologically modified drugs in the treatment of human neoplasms. 1. Introduction Current development of cancer treatment mainly relies on three avenues:(a)the identification of molecular targets for selective blockade of driver pathways in cancer cells or in tumour microenvironment,(b)immunemodulatory approaches which might enhance the antitumor specific immune response,(c)new delivery approaches in order to achieve higher bioavailability of anticancer agents. The topic of the current review is the nanoparticle albumin bound paclitaxel (nab-paclitaxel) development, which has opened a novel scenario in cancer treatment by the enhancement of paclitaxel delivery by the use of nanotechnology. 2. Taxane (First) Revolution of Cancer Therapy Taxanes are an important class of antitumor agents using solvent-based delivery vehicles. Paclitaxel (Bristol-Myers Squibb (New York, NY)) was identified in 1966, as an extract from Taxus brevifolia, obtained in a pure form in 1969 but its structure was published in 1971. Investigators faced several problems due to low concentration and structure complexities for low water solubility [1, 2] (Figure 1). Figure 1: Structure of paclitaxel (5 ,20-epoxy-1,2 ,4,7 ,13 -hex-ahydroxytan-11-en-9-one-4,10-diacetate2-benzoate-13-ester with (2 R.3 S)- N-benzoyl-3-phenyllioserine). In fact, only in 1979 Susan Horwitz discovered that paclitaxel has a unique mechanism of action and interest which was additionally stimulated when impressive activity was demonstrated in NCI tumor screening [3]. Paclitaxel is a diterpenoid pseudoalkaloid with formula C47H51NO14 ( ？Da) whose activity was demonstrated in different preclinical models. For antitumor activity the presence of the entire taxane molecule is required (Figure 2) for the inactivity of the ester and the tetraol formed by a low temperature cleavage of paclitaxel [4]. Figure 2: Taxane nucleus. Although the development of paclitaxel was hampered by limited availability of its primary source and the difficulties inherent to