Loadability and Releasing Profiles In Vitro and Pharmacokinetics In Vivo of Vinorelbine and Raltitrexed by CalliSpheres Beads.

Abstract

Background: This study investigated the loadability and releasing profiles of vinorelbine and raltitrexed from CalliSpheres® Beads (CB) in vitro, and further explored the pharmacokinetic features of vinorelbine and raltitrexed eluting CB in vivo. Materials and Methods: Ten milligrams vinorelbine and 0.2 mg raltitrexed were mixed with 0.15 g CB at two sizes (100-300 and 300-500 μm) for 24 h, respectively, to measure the loadability. Then vinorelbine/raltitrexed loading CBs were placed in 20% phosphate-buffered saline for 24 h to measure the release profiles. Transcatheter arterial chemoembolization (TACE) with 1 mg vinorelbine eluting CBs (two sizes respectively) and transcatheter arterial hepatic infusion (TAI) with 1 mg vinorelbine were performed in 9 rabbits (3 rabbits in each group). The above experiments were repeated with 0.2 mg raltitrexed. Results: Vinorelbine loading efficiency quickly reached 90% within 10 min with maximum loadability >90% by CB with both two sizes, and vinorelbine release rate gradually increased to ∼100% within 1 h. Raltitrexed loading efficiency gradually increased to >40% within 15 min, then slowly increased to >60% within 24 h, with maximum loadability <70% by CB with both sizes, and raltitrexed release rate gradually increased to >90% within 1 h. Besides, vinorelbine/raltitrexed eluting CB showed greatly decreased maximum serum concentration (Cmax) of the drug compared with TAI in rabbits with similar area under the curve (0-t), mean residence time (0-t), and half-time (T1/2). Conclusion: CB exhibits good loadability and an acceptable releasing profile for eluting vinorelbine and raltitrexed, and shows lower Cmax and numerically stable concentration than TAI.