Efficacy and Safety of Dual Paclitaxel and Sirolimus Nanoparticle-Coated Balloon
Kenji Kawai, Mohammed Tanjimur Rahman, Ryan Nowicki, Frank D. Kolodgie, Atsushi Sakamoto, Rika Kawakami, Takao Konishi, Renu Virmani, Vinod Labhasetwar, Aloke V. Finn
Abstract
• Dual API NPs, with a low dose of PTX in combination with SRL, demonstrated a synergistic effect in inhibiting VSMC proliferation via cell cycle arrest. • Dual API DCB–treated arteries in rabbit iliac model demonstrated a significantly lower percent of BrdU-positive nuclei in intima compared to PTX DCB–treated arteries at 5 days. • Dual API DCB–treated arteries displayed notably less VSMC loss than PTX DCB-treated arteries at 28-day follow-up. • In porcine coronary model, PTX DCB caused significantly greater myocardial injury and downstream embolism, whereas with dual API DCB there was no myocardial injury and infrequent incidence of downstream embolism. • Innovative dual API DCB demonstrated superior efficacy in suppressing intimal proliferation with minimal vascular injury and less downstream myocardial tissue injury. We evaluated a novel dual active pharmaceutical ingredient (API) drug-coated balloon (DCB), which consists of a coating of nanoparticles encapsulating low-dose paclitaxel (PTX) in combination with sirolimus in a synergistic ratio. Compared to the PTX DCB, the dual API DCB demonstrated similar inhibition of cell proliferation in vitro but at a significantly lower total drug dose (over 13 times lower than sirolimus nanoparticles). Animal experiments demonstrated that the dual API DCB is more effective in inhibiting intimal cell proliferation with insignificant downstream embolic effects and myocardial damage compared to the PTX DCB. These findings indicate that dual API DCBs have a high potential to demonstrate improved clinical outcomes and a greater safety profile than the PTX DCBs.