Albumin-Bound Nanoparticle Drug Nabs FDA Approval

January 20, 2005
Pharmaceutical Technology

Albumin-Bound Nanoparticle Drug Nabs FDA Approval

The USFood and Drug Administration has approved "Abraxane" for injectablesuspension (paclitaxel protein-bound particles for injectablesuspension) as the first protein-bound nanoparticledrug. The collaborative project of American Pharmaceutical Partners,Inc. (APP, Schaumburg, IL, andAmerican Bioscience Inc. (ABI, Santa Monica, CA), Abraxane consists of albumin-boundpaclitaxel nanoparticles for treating metastatic breast cancer aftercombination chemotherapy failure or relapse within six months ofadjuvantchemotherapy.

AbraxisOncology (the proprietary division of APP, that the key to successful delivery of the paclitaxelparticles is ABI's patented (2003) nanoparticle albumin-bound ("nab")technology, which binds water-insoluble compounds with albumin, aubiquitous protein in the human body and a natural carrier ofhydrophobic compounds, in a nanoparticle state. Tumors are known tonaturally "feed" by taking in and retaining albumin-bound nutrients.With the "nab" technology, chemotherapeutic drug molecules enclosedwithin albumin may be delivered through albumin-activated gp60receptors, which are used by tumors for taking in these nutrients. Thealbumin-activated gp60 "pathway," activated when albumin binds to gp60receptors, involves activation of the caveolae-1 protein during the"clustering" process (i.e.,the grouping of receptors upon albumin binding). This activationresults in the formation of caveolae (or "caves"), which entrap thegp60 receptors attached to the albumin complexes. Substances are thenmoved out of the bloodstream, across vessel walls, and into surroundingtissues. Because tumor tissues have a greater concentration of bloodvessels than healthy tissues do, scientists believe there is a greateropportunity for albumin-bound drugs to reach tumors rather than healthytissues. A novel manufacturing process retains the full biologicalproperties of albumin and helps to increase the bioavailability of theadministered drug product.

Incontrast to current taxane-based chemotherapies such as Taxol(Bristol-Meyers Squibb Co.), Abraxane does not require the use of toxicsolvents such as Cremophor-EL (BASF), which reportedly has beenassociated with some life-threatening reactions. Abraxaneadministration also does not require premedication such as thethree-day steroid treatment required before the administration ofcurrent commonly used taxanes. Such steroids also have been associatedwith adverse effects. Moreover, according to reported results, theabsence of solvents enables a higher dose (up to 50%, according toAPP/ABI announcements) of chemotherapy compared with solvent-basedtreatments.

Accordingto the American Cancer society, breast cancer is the leading overallcause of death in women between 20 and 59, causing an estimated 40,000deaths in 2004.

–Maribel Rios