Nanotech Revisited: – A Look At First Nanotechnology Based Drug Approved By FDA
DOXIL® (Doxorubicin hydrochloride liposome) is the first nanotechnology based drug approved by U.S Food and Drug Administration (FDA) for the treatment of patients with ovarian cancer, AIDS-related Kaposi’s sarcoma, and multiple myeloma. Doxil is not a new drug, but a reformulation of earlier known drug Doxorubicin; which is considered one of the most effective anticancer drugs developed till date.
What is Doxil:-
Doxil is pegylated liposomal formulation of Doxorubicin, the coating of Polyethylene glycol (pegylation) helps in evading detection and clearance by the immune system; increasing the circulation half life of Doxil in blood. Due to small size and surface coating, Doxil is able to penetrate compromised and leaky vasculature of tumors by a process known as Enhanced permeation and retention (EPR) effect.
• Doxil is used for the treatment of patients with ovarian cancer that has progressed or recurred after platinum-based chemotherapy.
• For the treatment of AIDS-related Kaposi’s sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy.
• In combination with bortezomib (VELCADE®) for the treatment of patients with multiple myeloma (both relapsed and refractory type) who have not previously received bortezomib.
Mode of Action:-
Mode of action of Doxil is same as that of doxorubicin, it acts on cells in three ways:-
• It intercalates between DNA strands, inhibiting DNA and RNA synthesis in rapidly dividing cells.
• Inhibits the enzyme topoisomerase II, preventing the relaxing of super-coiled DNA; blocking DNA and RNA synthesis.
• Forms iron-mediated free radicals, causing oxidative damage to DNA, proteins, and cell membrane lipids.
Mitochondrial membranes have high levels of the negatively charged phospholipid diphosphatidyl glycerol (cardiolipin) which are sensitive to oxidative damage effects of Doxorubicin. Heart muscles are enriched with mitochondria, resulting in high cardiotoxicity of the drug. Its other side effects include Typhlitis (infection of the bowel), neutropenia (decrease in white blood cells), alopecia (hair loss), hand-foot syndromes (reddening, swelling, and numbness on palms and soles).
Recently a generic version of Doxil was approved by U.S F.D.A after Doxil fell in short supply in late 2011. This generic version is made by Sun Pharma Global FZE, a subsidiary of India’s Sun Pharmaceutical Industries Ltd.
References: – www.doxil.com/assets/DOXIL_PI_Booklet.pdf
Image Credit: – http://www.doxil.com/ovarian-cancer/about-doxil