Multiple drug coated balloon exposures increase arterial permeability and drug retention

Background: It is thought that increased dose or number of drug-coated balloon (DCB) inflations increases drug delivery and tissue retention – this however has never been validated and this we examined.

Methods: Paclitaxel (PTX) coated balloons (W.L. Gore, Flagstaff AZ) with 4.1 (5x40 mm) or 3.6 µg/mm² (6x40 mm) PTX were inflated for 60 sec once or three DCB sequentially at the same angiographic site in 30 Yorkshire swine peripheral arteries. Animals were euthanized from 1h to 30 days (n=4-8/time point) and arteries collected for bioanalysis. The time series of total arterial drug for each treatment group was fit to a bi-exponential model with zero plateau (R²≥0.999) and fits compared using a paired t-test.

Results While ~75% of the PTX load was released from the balloons independent of the number of inflations per artery, the amount deposited in the wall and retained over time differed. Arteries in the clinical single dose group absorbed only 72.1±0.6 µg PTX, of which 97% was cleared with a half-life of 8 hours. Surprisingly, three exposures produced 6.6-fold more PTX, twice the difference from dose alone (478±8.1 µg, p<0.0001) and what was deposited was cleared slower; 92% with a half-life of 13 hours (p=0.0028).

Conclusions Tissue retention from DCB benefits from repeat inflations but NOT due to increased dose exposure - suggesting that repeated dilation may prepare the artery for enhanced absorption and/or overcome restrictions of single dose retention. These studies beg further evaluation in disease models and reevaluation of clinical use protocols for DCB.