Design and validation of a poly-L-lysine dendrimer-based rapamycin delivery system for intracranial drug-coated balloons.

Rapamycin can be used as a coating on balloon catheters but faces challenges such as poor tissue retention and significant drug loss during delivery. In this study, a third-generation poly-L-lysine (G3 PLL) dendrimer-based delivery system was developed for intracranial drug-coated balloons to modulate drug loading and local pharmacokinetic behavior. Using a rabbit carotid artery model, the residual drug on the balloon surface after expansion and rapamycin concentrations in vascular tissue and plasma were evaluated immediately and on days 1, 3, and 7. The results showed that the post-expansion residual drug rate on the balloon surface was 4.288 ± 0.788%, i.e., lower than that of conventional paclitaxel-coated balloons (15.8 ± 5.5%). The vascular tissue drug concentrations demonstrated a sustained release profile, starting at 719.134 ± 2.584 μg/g and remaining at 485.716 ± 3.164 μg/g on day 7. The peak plasma concentration (0.791 ± 0.018 μg/mL) was well below the known toxic threshold of 5 μg/mL. The proposed system enabled controlled intramural exposure while limiting systemic drug levels, reflecting modulation of drug disposition following transient balloon contact. In conclusion, these findings support the feasibility of a dendrimer-enabled formulation strategy for localized vascular drug delivery with favorable pharmacokinetic characteristics for intracranial arterial stenosis.