DOXIL (doxorubicin hcl liposome injection)

DOXIL (doxorubicin hcl liposome injection) is doxorubicin HCl encapsulated in long-circulating STEALTH® liposomes. Liposomes are microscopic vesicles composed of a phospholipid bilayer that are capable of encapsulating active drugs. The STEALTH® liposomes of DOXIL (doxorubicin hcl liposome injection) are formulated with surface-bound methoxypolyethylene glycol (MPEG), a process often referred to as pegylation, to protect liposomes from detection by the mononuclear phagocyte system (MPS) and to increase blood circulation time.

It is an anthracyclic antibiotic, closely related to the daunomycin, and like all anthracyclines, it works by intercalating DNA, with the most serious adverse effect being life-threatening heart damage. It is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas.

Molecular mechanism:

1. Doxorubicin helps to stabilize complexes containing double-stranded DNA and the enzyme topoisomerase II: this enzyme then cuts both of the DNA strands, which leads to the death of both normal cells (predominantly via topoisomerase IIβ) and in tumour cells that are susceptible to the drug (predominantly via topoisomerase IIα), thus accounting for both the toxicity and anti-tumour efficacy of doxorubicin.

2. Doxorubicin increases the production of ceramides inside cells, which leads to the latent transcription factor CREB3L1 translocating from the endoplasmic reticulum to the Golgi apparatus. Two proteases (S1P and S2P) then cut the CREB3L1 protein; and its amino-terminal fragment then migrates into the nucleus, where it acts as a transcription factor to activate the CDNK1A locus and additional genes. This leads to increased expression of the p21 protein along with other proteins that inhibit the proliferation of tumour cells.

Reference:
1. http://elife.elifesciences.org/content/1/e00387
2. http://www.rxlist.com/doxil-drug/clinical-pharmacology.htm
3. www.doxil.com