A cell-based drug delivery system for lung targeting: I. Preparation and pharmacokinetics.
A drug-loaded tumor cell (DLTC) system has been developed for lung metastasis-targeting drug delivery. Doxorubicin was loaded into B16-F10 murine melanoma cells (96 microg/10(6) cells). The loading process led to the death of all the carrier cells. The diameter of DLTC was 15.03+/-2.36 microm (mean +/- SD). The amount and rate of doxorubicin being released from the DLTC mainly depended on the drug loading and carrier cell concentration. Over a 6-month storage in phosphate buffered saline (PBS) at 4 degrees C, the decrease in intracellular drug concentration and the carrier cell number were less than 25% and 5%, respectively. After a bolus injection of 30 microg doxorubicin in either DLTC form or free solution into the mice tail veins, drug deposit in the lung from DLTC was 3.6-fold of that achieved by free drug solution. The latter resulted in higher drug content in liver and spleen. Extensive trypsinization of DLTC reduced its lung targeting effect by 30%, and the density of surface adhesion molecule GM3 on DLTC surface by 25%. In conclusion, this DLTC system demonstrated a lung-targeting activity that may be partially attributed to its specific surface characteristics.
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
Runyan
K
K
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