pH-Sensitive, Long-Circulating Liposomes as an Alternative Tool to Deliver Doxorubicin into Tumors: a Feasibility Animal Study.

PURPOSE: Therapeutic agents used in chemotherapy have low specificity leading to undesired severe side effects. Hence, the development of drug delivery systems that improve drug specificity, such as liposome moieties, is an alternative to overcome chemotherapy limitations and increase antitumor efficacy. In this study, the biodistribution profile evaluation of pH-sensitive long-circulating liposomes (SpHL) containing [99m Tc]DOX in 4T1 tumor-bearing BALB/c mice is described.

PROCEDURES: [99m Tc]DOX was radiolabeled by direct method. Liposomes were prepared and characterized. [99m Tc]DOX was encapsulated into liposomes by freezing and thawing. Circulation time for SpHL-[99m Tc]DOX was determined by measuring the blood activity from healthy animals. Biodistribution studies were carried out in tumor-bearing mice at 1, 4, and 24 h after injection.

RESULTS: Blood levels of the SpHL-[99m Tc]DOX declined in a biphasic manner, with an α half-life of 14.1 min and β half-life of 129.0 min. High uptake was achieved in the liver and spleen, due to the macrophages captured. Moreover, tumor uptake was higher than control tissue, resulting in high tumor-to-muscle ratios, indicating higher specificity for the tumor area.

CONCLUSION: [99m Tc]DOX was successfully encapsulated in liposomes. Biodistribution indicated high tumor-to-muscle ratios in breast tumor-bearing BALB/c mice. In summary, these results showed the higher accumulation of SpHL-[99m Tc]DOX in the tumor area, suggesting selective delivery of doxorubicin into tumor.