Coating and Pharmacokinetic Evaluation of Air Spray Coated Drug Coated Balloons

Abstract

Drug coated balloons (DCB) are becoming the standard-care treatment for peripheral arterial disease (PAD). DCB use excipients to transfer and retain anti-proliferative drugs, such as paclitaxel. Excipients thus play a vital role in the design and function of DCB, however methods to coat balloons with excipients and anti-proliferative drugs remain unknown. The goal of this study was to thus develop an approach to coat and evaluate DCB for various excipients. An air sprayer method was developed to deposit paclitaxel and various excipients onto non-coated commercially available angioplasty balloons. The coating of the angioplasty balloons was evaluated for drug deposition and coating efficiency using high performance liquid chromatography tandem mass spectrometry. Drug transfer and retention of the coated angioplasty balloons into arterial segments were evaluated ex vivo using harvested pig arteries in a pulsatile flow bioreactor. The air sprayer method successfully delivered varying excipients including bovine serum albumin (BSA), urea and iohexol. The air spray method was configured to coat four angioplasty balloons simultaneously with paclitaxel and iohexol with an average paclitaxel load of 4.0 ± 0.70 µg/mm². The intra-day (within) and inter-day (between) coating precisions, defined as relative standard deviation (RSD), was 17.2 and 15.5%, respectively. Ex vivo deployment of iohexol-paclitaxel DCB yielded an arterial paclitaxel concentration of 123.4 ± 44.68 ng/mg (n = 3) at 1 h, 126.7 ± 25.27 ng/mg (n = 3) at 1 day, and 12.9 ± 12.88 ng/mg (n = 3) at 7 days. This work provides proof-of-concept of a quick, inexpensive approach to coat commercially available angioplasty balloons with paclitaxel and various excipients.

Keywords: Coating; Drug coated balloon; Iohexol; Paclitaxel; Pharmacokinetics.

Figure 1

Setup of mounted balloons for air spray coating. A) Four balloons were mounted vertically in offset positions. An air sprayer was then utilized to coat balloons with drug solution (side view). B) To ensure consistent coating, the four mounted balloons were spray coated at 4 directions starting at 0°, followed by 90°, 180°and 270°(Top view). C) At all coating locations (1–4) all four balloons are exposed to the spray area and no balloons are covered by the others.

Figure 2

Angioplasty balloon before and after coating. A) Uncoated balloon, B) Iohexol-paclitaxel coated balloon.

Figure 3

Scanning electron micrograph of excipient coatings onto coverslips. A) Urea [1000 mg/mL], B) BSA [400 mg/mL], C) Iohexol.

Figure 4

Scanning electron micrograph of paclitaxel coatings onto coverslips. A) Paclitaxel [40 mg/mL], B) iohexol followed by paclitaxel [40 mg/mL].

Figure 5

Scanning electron micrograph of paclitaxel coated balloons. A) iohexol-paclitaxel coating B) SeQuent Please DCB.

Figure 6

Artery mounted in bioreactor to simulate arterial deployment. (A) Inner artery is affixed to plastic fittings via suture. An outer, Sylgard sheath is affixed with o-rings. The artery is bathed in cell culture media inside and between the artery and Sylgard sheath. (B and C) Diameter measurement of explanted arteries. (B) An ultrasound probe can be directly placed on the outer sleeve of the bioreactor housing to measure the diameter. (C) Ultrasound image showing the inner diameter of the explanted artery (markers outlined in red). Recorded graphs of (D) flow rate and (E) pressure within the bioreactor system.