Pegylated Liposomal Doxorubicin – Lower Cardiotoxicity

Pegylated liposomal doxorubicin – lower cardiotoxicity

Cardiotoxicity is an important adverse effect of doxorubicin (adriamycin) which is an effective anti cancer drug. A special formulation of doxorubicin to reduce its toxicity is known as pegylated liposomal doxorubicin. In this formulation, the drug is encapsulated in bilayer lipid sphere which is known as a liposome. Polyethylene glycol derived phospholipid liposomes have been shown to have five fold longer circulation time in blood and increased accumulation in tumors [1]. Chemical structure and size (around 100 nanometers) of this liposome selectively interfered with its entry into the vasculature of normal organs like the heart. Hence pegylated liposomal doxorubicin has a potential to have better therapeutic effect on cancer cells and lower cardiotoxicity [2].

PEGylation is the process of attachment of PEG (polyethylene glycol) polymer to another molecule by covalent bonding. Pegylation increases the circulation time by reducing renal clearance as the size of the molecule in solution (hydrodynamic size) is increased. While pegylated liposomal doxorubicin can pass out and leak into the tumour tissue with abnormal vasculature, it is less likely to enter through the normal vasculature of the normal tissue.

Toxicities of pegylated liposomal doxorubicin

Toxicities noted during pegylated liposomal doxorubicin treatment were stomatitis, palmoplantar erythrodysesthesia and hematological abnormalities [3].

References

1. Papahadjopoulos D, Allen TM, Gabizon A, Mayhew E, Matthay K, Huang SK, Lee KD, Woodle MC, Lasic DD, Redemann C. Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy Proc Natl Acad Sci U S A. 15;88:11460-4.
2. Orditura M, Quaglia F, Morgillo F, Martinelli E, Lieto E, De Rosa G, Comunale D, Diadema MR, Ciardiello F, Catalano G, De Vita F. Pegylated liposomal doxorubicin: pharmacologic and clinical evidence of potent antitumor activity with reduced anthracycline-induced cardiotoxicity Oncol Rep. 2004;12:549-56.
3. Minisini AM, Andreetta C, Fasola G, Puglisi F. Pegylated liposomal doxorubicin in elderly patients with metastatic breast cancer. Expert Rev Anticancer Ther. 2008;8:331-42.