Inhalation delivery of topotecan is superior to intravenous exposure for suppressing lung cancer in a preclinical model

Drug Delivery
Philip J KuehlMathewos Tessema

Abstract

Intravenous (IV) topotecan is approved for the treatment of various malignancies including lung cancer but its clinical use is greatly undermined by severe hematopoietic toxicity. We hypothesized that inhalation delivery of topotecan would increase local exposure and efficacy against lung cancer while reducing systemic exposure and toxicity. These hypotheses were tested in a preclinical setting using a novel inhalable formulation of topotecan against the standard IV dose. Respirable dry-powder of topotecan was manufactured through spray-drying technology and the pharmacokinetics of 0.14 and 0.79 mg/kg inhalation doses were compared with 0.7 mg/kg IV dose. The efficacy of four weekly treatments with 1 mg/kg inhaled vs. 2 mg/kg IV topotecan were compared to untreated control using an established orthotopic lung cancer model for a fast (H1975) and moderately growing (A549) human lung tumors in the nude rat. Inhalation delivery increased topotecan exposure of lung tissue by approximately 30-fold, lung and plasma half-life by 5- and 4-folds, respectively, and reduced the maximum plasma concentration by 2-fold than the comparable IV dose. Inhaled topotecan improved the survival of rats with the fast-growing lung tumors from 7 to 80% ...Continue Reading

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Citations

Jun 20, 2021·International Journal of Pediatric Otorhinolaryngology·Dylan Z ErwinAndrew D Meyer
Aug 28, 2021·International Journal of Pharmaceutics·Suyash M PatilNitesh K Kunda
Sep 2, 2021·AAPS PharmSciTech·Kimberly B ShepardMichael Banks

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