Doxorubicin encapsulated in phospholipid copolymer penetrates solid tumors

NEW YORK (Reuters Health) - A novel drug delivery system devised by scientists in China improves the penetration of doxorubicin into solid tumors while reducing its systemic toxicity, according to their article in the Journal of the National Cancer Institute for July 4.

The drug carrier consisted of hydrophilic polyethylene glycol (PEG) and hydrophobic phosphatidylethanolamine (PE), Dr. Wei Liang and colleagues at the Chinese Academy of Sciences in Beijing report in their paper. They state that the copolymer forms micelles about 10 to 20 nm in size.

Compared with "naked" doxorubicin, the "nanoassemblies" containing the drug were more rapidly internalized by cultured non-small-cell lung carcinoma cells. Lower concentrations were required for cytotoxic effects.

The researchers' in vivo studies involved mice inoculated subcutaneously with Lewis lung carcinoma cells. After 5 days, they were treated intravenously with free doxorubicin or doxorubicin in micelles.

Subsequent tumor growth rates and metastasis were "dramatically decreased," and survival was substantially increased. Dr. Liang's team also observed that encapsulated doxorubicin was associated with increased penetration into tumor cells.

The encapsulated doxorubicin was significantly less toxic than free doxorubicin, causing weight gain instead of weight loss, maintaining white blood cell counts, and minimizing the extent of myocarditis.

"The tightly packed structure of (PEG-PE encapsulated doxorubicin) may be the source of its high antitumor activity and low systemic toxicity," Dr. Liang and colleagues indicate. "This property should be considered in the construction of nanoassemblies as delivery systems for other chemotherapeutic models."

In an editorial, Dr. Matthew R. Dreher from the National Institutes of Health in Bethesda, Maryland, and Dr. Ashutosh Chilkoti from Duke University in Durham, North Carolina, applaud the "impressive preclinical results" attained by Dr. Liang's group.

At the same time, they maintain, more answers regarding their methodology and a lot more research to establish the behavior of encapsulated doxorubicin will be required before the nanoassemblies can be considered for clinical use.