A cell-based drug delivery system for lung targeting: II. Therapeutic activities on B16-F10 melanoma in mouse lungs.
The in vitro and in vivo anticancer activities of doxorubicin-loaded B16-F10 murine melanoma cells (DLTC) were evaluated. DLTC showed similar growth-inhibitory effects against live B16-F10 cells with doxorubicin solution in cell culture system, with the IC50 of 0.11 microM and 0.17 microM, respectively. However, DLTC demonstrated higher effectiveness than the free solution in treating mouse lung cancer caused by live B16-F10 cells. Syngeneic C57BL mice were inoculated intravenously with live B16-F10 cells first, and then received daily treatment of intravenous injections of doxorubicin in either DLTC or free solution form. Compared with the control group treated with phosphate-buffered saline, DLTC eradicated almost all the lung cancer colonies (>99%), while the free solution form reduced the colonies by 61%, when the treatment was given at an early stage. If the treatment started after the establishment of micrometastatic colonies in the mouse lungs, DLTC and free solution treatment resulted in 85% and 30% cancer reduction, respectively. Additional experiments demonstrated that the reduction of lung cancer colonies by DLTC was related to the initial treatment time: the earlier the treatment, the greater the effect. In conclusion, DLTC showed better therapeutic outcomes than free solution form in treating lung cancer of our animal model.
Shao
J
J
Department of Pharmacy and Administrative Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, New York 11439, USA. shaoj@stjohns.edu
DeHaven
J
J
Lamm
D
D
Weissman
D N
DN
Malanga
C J
CJ
Rojanasakul
Y
Y
Ma
J K
JK
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002448:Cell Adhesion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D005434:Flow Cytometry; D008175:Lung Neoplasms / Q000188:drug therapy*; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D014018:Tissue Distribution; D014357:Trypsin / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D014357:Trypsin