Pharmacokinetic and Stability Analysis of an Inhalable Formulation of Camptothecin for the Treatment of Lung Cancer

The focus of this work was to create a dry-powder camptothecin (CPT) formulation that could be inhaled and potentially developed into a lung cancer therapeutic. CPT and CPT analogs have been shown to be effective in treating lung cancers.  However, the physical properties of CPT have made it difficult to formulate into a deliverable therapeutic, limiting its utility in the clinic. CPT nanocrystals with an approximate diameter of 120 nm ± 80 nm were spray-dried with 10,000-dalton molecular-weight dextran (Dex10), creating particles of the correct size for dispersal into the lungs upon inhalation. Impaction analysis of the powder revealed that the mass median aerodynamic diameter (MMAD) of the particles was 2.7 µm and the fine particle fraction (FPF) was 78%. The powder was aerosolized and delivered to rats using a nose-only inhalation chamber at Lovelace Respiratory Research Institute (LRRI). Rats received a high or low inhaled dose of powder or an intravascularly (IV)-delivered dose, to compare CPT exposure to the lungs through inhalation and IV dosing.

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