Adhesive polyelectrolyte coating on PLGA particles prolongs drug retention to vessel lesion

Restenosis, the re-narrowing of blood vessels after drug-coated balloons (DCBs), remains a major clinical issue. While rapamycin is the current clinical option for preventing restenosis due to its effectiveness and low toxicity, its delivery is limited by poor tissue absorption and rapid clearance, leading to suboptimal drug retention. Here, we developed the adhesive-polyelectrolyte-coated poly(lactic-co-glycolic acid) (PLGA) particles using in-situ UV-triggered polymerization, encapsulating rapamycin. This system combines PLGA's sustained release with a robust adhesive coating that enhances vascular wall binding, by hydrogen bonding and covalent bonding. Rapamycin retention improved by 835 % in vitro (1 week) and 525 % in vivo (4 weeks) compared to uncoated particles. This approach offers a promising strategy to enhance rapamycin delivery, improving the safety and efficacy of DCBs in treating vessel obstruction.