Effects of borneol on pharmacokinetics and tissue distribution of tetramethylpyrazine in transdermal patch

Tetramethylpyrazine (TMP), a potent coronary vasodilator, enhances myocardial perfusion and shows promise for treating cardiovascular disorders. Its clinical utility is limited, however, by the short half-life of conventional tablets and injections, which necessitates frequent dosing. To overcome this drawback, we developed a transdermal patch that co-loadsTMP and borneol (BO-TMP). After optimization, patches containing 3% borneol as a permeation enhancer, exhibiting the highest cumulative penetration amount of TMP (6.80 mg·cm^-2 over 24 h) in vitro. Pharmacokinetic profiling revealed that borneol markedly improved TMP exposure. C_max rose from (1.96 ± 0.27) to (2.88 ± 0.72) mg/L, and AUC_0-t expanded from (47.73 ± 6.93) to (73.18 ± 13.86) mg/L*h in plasma; C_max rose from (12.99 ± 2.28) to (15.33 ± 4.24) mg/L, and AUC_0-t expanded from (220.86 ± 53.88) to (374.55 ± 111.84) mg/L*h in skin, C_max rose from (0.87 ± 0.12) to (6.20 ± 0.84) mg/L, and AUC_0-t expanded from (13.08 ± 3.35) to (79.80 ± 16.31) mg/L*h in heart when BO-TMP patches were administrated compared with TMP patches. Tissue distribution studies demonstrated that borneol redirected TMP distribution, shifting the order of tissue abundance from liver > kidney > brain > spleen > heart > lung to liver > kidney > heart > brain > spleen > lung, and thus enriched the drug at its therapeutic site. By selectively heightening cardiac exposure, the BO-TMP patch transform TMP into a cardiovascular-focused therapy, offering a convenient, long-acting dosage from with the potential to enhance efficacy and improve patient outcomes.