A new ex vivo model for optimizing distribution of therapeutic aerosols: the (inverted) bovine urinary bladder.

BACKGROUND

Development of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) requires adequate preclinical models.

METHODS

The model should be easy to use, reproducible and cost-effective. It should have a volume similar to the human abdominal cavity, and an oval shape. The inner surface should be lined with serosa. The model should allow pharmacological and biological analysis, including histology. No living animals should be used.

RESULTS

The fresh urinary bladder is explanted from an adult bovine in the slaughterhouse. A 4-cm incision is performed into the bladder neck. The bladder can be inverted through the incision, which allows exposition of the serosa on its inner side. A balloon trocar is inserted through the incision and a ligature placed, ensuring full tightness. The therapeutic capnoperitoneum is installed. The bovine bladder has a volume somewhat smaller (2-3 L) than the human abdominal cavity (3-5 L). Costs are minimal. There is no significant bacteriological contamination. Manipulation is simple.

CONCLUSIONS

The (inverted) bovine urinary bladder is an innovative and versatile ex vivo model for optimizing drug delivery with therapeutic aerosols both onto the mucosa or the serosa. This model can be used for pharmaceutical Quality-by-Design approaches and will replace a large number of experiments in the animal.