Pulmonary targeting microparticulate camptothecin delivery system: anticancer evaluation in a rat orthotopic lung cancer model

• DOI: 10.1097/cad.0b013e328332a322
• Publication Date: 2009-12-04T08:19:07Z
• Authors: Piyun Chao; Manjeet Deshmukh; Hilliard L. Kutscher; Dayuan Gao; Sujata Sundara Rajan; Peidi Hu; Debra L. Laskin; Stanley Stein; Patrick J. Sinko
• Keywords: Camptothecin; Bolus (digestion)

Large (>6 microm) rigid microparticles (MPs) become passively entrapped within the lungs after intravenous (i.v.) injection making them an attractive and highly efficient alternative to inhalation for pulmonary delivery. In this study, PEGylated 6 microm polystyrene MPs with multiple copies of norvaline (Nva) alpha-amino acid prodrug camptothecin (CPT) were prepared. Surface morphology was characterized using a scanning electron microscope. CPT released from CPT-Nva-MPs over 24 h in rat plasma at 37 degrees C. In-vivo concentrations low (approximately 1 ng/ml or less) constant period 4 days single i.v. as compared high but short-lived systemic exposures free CPT. This suggests that sustained local achieved lung administration MP delivery system. Anticancer efficacy evaluated orthotopic cancer animal model bolus Animals receiving (2 mg/kg) (0.22 mg/kg 100 MPs) found have statistically significant smaller areas (P<0.05 0.01, respectively) than untreated animals. addition, 40% animals be cancer. The dose targeted 10 times lower CPT, more effective reducing amount cancerous areas. conclusion, able achieve systemically administered resulting improvement anticancer