title: Paclitaxel liposome aerosol treatment induces inhibition of pulmonary metastases in murine renal carcinoma model.
abstract: 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.
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA. koshkina@bcm.tmc.edu
authors.forename: N V
authors.initials: NV
authors.lastname: Koshkina
authors.forename: J C
authors.initials: JC
authors.lastname: Waldrep
authors.forename: L E
authors.initials: LE
authors.lastname: Roberts
authors.forename: E
authors.initials: E
authors.lastname: Golunski
authors.forename: S
authors.initials: S
authors.lastname: Melton
authors.forename: V
authors.initials: V
authors.lastname: Knight
mesh_terms: 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
chemical_list: D000336:Aerosols; D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D017239:Paclitaxel