Doxorubicin Treatment Avoids Heart Damage by Specific Liposomal Delivery to the Liver

Liposomes expressing a peptide sequence that specifically targets them to liver cells were used to deliver highly effective doses of the chemotherapeutic drug doxorubicin with few toxic effects on other organs.

Previous work had demonstrated that liposomes, containing an amino acid sequence copied from the malaria parasite Plasmodium that binds to hepatic heparan sulfate glycosaminoglycan, showed effective targeting to liver hepatocytes. In the current study, investigators from the University of California, Irvine (USA) filled the liposomes with the cancer drug doxorubicin. Doxorubicin is an effective chemotherapeutic agent, but the serious heart damage that results from systemic administration places limits on the dosage that a patient can receive.

After intravenous administration to mice, organs were harvested and the doxorubicin content extracted and measured by fluorescence intensity and by fluorescence microscopy. Data published in the August 5, 2009, online edition of the International Journal of Pharmaceutics revealed that the liposomal doxorubicin was recovered almost entirely from the liver, with only trace amounts detectable in the heart, lung, and kidney. Fluorescence microscopy demonstrated doxorubicin preferentially in hepatocytes, also in nonparenchymal cells of the liver, but not in cells of heart, lung, or kidney. The doxorubicin was localized within liver cell nuclei within five minutes after intravenous injection.

The authors concluded that, "With the composition described here, the doxorubicin was rapidly released from the liposomes without the need for an externally supplied stimulus. These studies demonstrated that liposomal doxorubicin can be effectively delivered to hepatocytes by targeting the heparan sulfate glycosaminoglycan of liver tissue.”

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University of California, Irvine