(mPEG) containing Antitumor antibiotic Interferes with cell division Half life 55 hours in humans ~ 100 nm size Produced by Ben Venue Labs, - Bedford, OH, contract mfg Div. of BoeringerIngelheim Distributed by Centocor Ortho Biotech, Inc – Horsham, PA private, Div. of J&J STEALTH ® and DOXIL ® are trademarks of ALZA Corporation, Div. of J&J
Abraxane - Approved Approved for Breast Cancer Albumin-bound Paclitaxel Paclitaxel – powerful anticancer drug – not water soluble Abraxane is water soluble – reduces treatment to 30 min from 3 hrs for solvent version & its side effects ~130 nm American Pharmaceutical Partners and American BioScience, Inc – approved by FDA 05Jan05 Produced by Abraxis BioScience – Los Angeles, CA
Drugs are delivered to tumors by leaky junctions in the blood vessels.
Drugs also bind to albumin and are transported in the blood and delivered to tumors. This is accomplished first by taking advantage of the transport system (gp60 pathway) across the endothelial cells and then concentrating within the tumor interstitium by its affinity for SPARC (Secreted Protein Acidic and Rich in Cysteine).
Finally, the water insolubility of many active chemotherapy agents is overcome by using proteins instead of additional chemicals to dissolve the active drug.
Coroxane – In Phase 2 Trials Angioplasty, removal of plaque in arteries, short-term solution Next, a bare metal stent is placed to keep the vessel from narrowing. Drug-eluting stents containing either paclitaxel or rapamycin have been approved for treatment of restenosis in the coronary arteries. The drug helps to prevent hardening of the artery in conjunction with the stent. COROXANE™, a microtubule stabilizer, is being developed by Abraxis to be used in conjunction with stents to prevent arterial restenosis.
Coroxane – In Phase 2 Trials Coronary Artery Restenosis: ~800,000/yr procedures of coronary artery stenting in the US alone. While drug-eluting stents are encouraging, may be complications after surgery, weakening of the artery wall, blood clots, and an increased risk of heart attack when the vessel doesn’t heal completely. COROXANE™ is currently in phase 2 trials for CAR. Peripheral Artery Disease of the lower extremities is common in older adults, caused by thickening of the blood vessel wall that limits blood flow to the legs. Standard treatment is angioplasty alone. Surgical placement of stents in the blood vessel has had limited success. Phase 2 studies are focusing on the use of COROXANE™ along with angioplasty of the affected blood vessel. Produced by Abraxis BioScience – Los Angeles, CA
Examples of Nanocarriers for Targeting Cancer A whole range of delivery agents are possible but the main components typically include a nanocarrier, a targeting moiety conjugated to the nanocarrier, and a cargo (such as the desired chemotherapeutic drugs). Schematic diagram of the drug conjugation and entrapment processes. The chemotherapeutics could be bound to the nanocarrier, as in the use of polymer–drug conjugates, dendrimers and some particulate carriers, or they could be entrapped inside the nanocarrier.
Mechanisms by which Nanocarriers Can Deliver Drugs to Tumors Polymeric nanoparticles are shown as representative nanocarriers (circles). Passive tissue targeting is achieved by extravasation of nanoparticles (NP) through increased permeability of the tumor vasculature and ineffective lymphatic drainage (EPR effect).
Mechanisms by which Nanocarriers Can Deliver Drugs to Tumors Active cellular targeting (inset) can be achieved by functionalizing the surface of NP with ligands that promote cell-specific recognition and binding. The nanoparticles can (i) release their contents in close proximity to the target cells; (ii) attach to the membrane of the cell and act as an extracellular sustained-release drug depot; or (iii) internalize into the cell.