Paclitaxel liposome aerosol treatment induces inhibition of pulmonary metastases in murine renal carcinoma model.
The present studies were undertaken to evaluate the pulmonary pharmacokinetics and therapeutic efficacy of paclitaxel (PTX) administered by aerosol. PTX was encapsulated into dilauroylphosphatidylcholine liposomal formulations (PTX-DLPC). The deposition and clearance of PTX-DLPC in the lungs administered by aerosol or i.v. at comparative doses was performed, and PTX was quantitatively determined in tissue extracts by high-performance liquid chromatography analysis. The murine renal carcinoma (Renca) pulmonary metastases model was used to determine the therapeutic effect of drug formulation administered by aerosol. PTX-DLPC aerosols were generated with the Aero-Mist jet nebulizer (cis-USA). The most effective schedule of treatment was when mice inhaled the drug for 30 min 3 days per week. There was a significant reduction of the lung weights and reduced number of visible tumor foci on the lung surfaces of mice treated with PTX aerosol (P < 0.004 and P < 0.01, respectively) compared with control groups. Inhalation of PTX-DLPC also led to prolonged survival in mice inoculated with Renca cells. The results of the present studies demonstrate the therapeutic potential of aerosol technology for lung cancer treatment.
Koshkina
N V
NV
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA. koshkina@bcm.tmc.edu
Waldrep
J C
JC
Roberts
L E
LE
Golunski
E
E
Melton
S
S
Knight
V
V
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000473:pathology; D006224:Cricetinae; D007275:Injections, Intravenous; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology; D008081:Liposomes; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015996:Survival Rate; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000336:Aerosols; D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D017239:Paclitaxel