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Cancer Biotherapy & Radiopharmaceuticals Nov 2023This study investigated the raltitrexed loading method, compatible stability with contrast agent, release profiles, and morphological properties of CalliSpheres, DC...
This study investigated the raltitrexed loading method, compatible stability with contrast agent, release profiles, and morphological properties of CalliSpheres, DC Bead, and HepaSphere. The amounts of raltitrexed added, loading medium, loading condition, and drug concentrations were investigated as factors influencing drug loading efficiency. Compatible stability with iopamidol was tested. Release profiles were accessed by a flowthrough apparatus system. Morphological properties were evaluated by a scanning electron microscope (SEM). Diameters were measured by a laser diffraction particle size analyzer. With the optimized method, the amount of raltitrexed loading to a marketed drug-eluting beads (DEBs) package was 2.67 mg for CalliSpheres, 2.34 mg for DC Bead, and 3.19 mg for HepaSphere. For all three DEBs, the drug leak rate was >50% within 2 h after mixing with iopamidol, and the time to reach 75% of the release plateau was within 10 min. Diameters increased after drug loading. Drug crystals were observed on the surface of DEBs in SEM. The amount of drug loading could meet clinical requirements by the optimized method. All three raltitrexed-loaded DEBs showed poor compatible stability with iopamidol, as well as rapid drug release performance, which should be noticed in clinical practice.
Topics: Humans; Iopamidol; Chemoembolization, Therapeutic; Quinazolines; Thiophenes; Microspheres
PubMed: 34767737
DOI: 10.1089/cbr.2021.0251 -
Cancer Biotherapy & Radiopharmaceuticals Oct 2023This study investigated the loadability and releasing profiles of vinorelbine and raltitrexed from CalliSpheres Beads (CB) , and further explored the pharmacokinetic...
This study investigated the loadability and releasing profiles of vinorelbine and raltitrexed from CalliSpheres Beads (CB) , and further explored the pharmacokinetic features of vinorelbine and raltitrexed eluting CB 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. 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). CB exhibits good loadability and an acceptable releasing profile for eluting vinorelbine and raltitrexed, and shows lower Cmax and numerically stable concentration than TAI.
Topics: Animals; Rabbits; Vinorelbine; Carcinoma, Hepatocellular; Liver Neoplasms; Chemoembolization, Therapeutic
PubMed: 32614660
DOI: 10.1089/cbr.2019.3360