Evaluation of the in vitro elution characteristics of carboplatin-impregnated calcium sulfate beads

Carboplatin;calcium sulfate;impregnated beads;local delivery;sustained release

Tulipan, Rachel Jane ; Fan, Timothy M., ; ,Garrett, Laura D ; Phillips ; Heidi

关键词: Carboplatin;    calcium sulfate;    impregnated beads;    local delivery;    sustained release;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/92654/TULIPAN-THESIS-2016.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Pilot Study:Objective: To characterize the elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CSH) beads in vitro.Sample:Sixty carboplatin-impregnated CSH beads and 9 CSH beads without added carboplatin (controls) Procedures: Carboplatin-impregnated CSH beads (each containing 4.6 mg carboplatin [2.4 mg platinum]) were placed into separate 10 mL plastic tubes containing 5 mL of PBS in groups of 1, 3, 6, or 10; 3 control beads were placed in a single tube of PBS at the same volume. Experiments were conducted in triplicate at 37 °C and pH 7.4 with constant agitation. Eluent samples were collected at 1, 2, 3, 6, 12, 24, and 72 hours. Samples were analyzed for platinum content by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Results: The mean concentration of platinum released per carboplatin-impregnated bead over 72 hours was 445.3 mg/L. Cumulative concentrations of platinum eluted increased as the number of beads per tube increased. There was a significant difference in platinum concentrations over time, with values increasing over the first 12 hours and then declining for all tubes. There was also a significant difference in percentage of total incorporated platinum released into tubes with different numbers of beads: the percentage eluted of platinum was higher in tubes containing 1 or 3 beads than in those containing 6 or 10 beads.Conclusions and Clinical Relevance: Carboplatin-impregnated CSH beads eluted platinum over 72 hours. Further studies are needed to determine whether implantation of carboplatin-impregnated CSH beads results in detectable levels of platinum systemically and whether the platinum concentrations eluted locally are toxic to tumor cells. Experiment 2: Objective: To characterize the long-term elution of platinum from carboplatin-impregnated CSH beads in vitro using two distinct sampling methods.Sample: Carboplatin-impregnated CSH beads containing 4.6 mg carboplatin/beadProcedures: Method 1: Three carboplatin-impregnated CSH beads were placed into 10 mL plastic tubes with 5 mL of PBS at 37 C and pH 7.4 with constant agitation. PBS was sampled by evacuation of all 5 mL eluent at 1, 2, 3, 6, 9, and 12 hours and 1, 2, 3, 6, 9, 12, 15, 18, 22, 26, and 30 days. The fluid was then replaced with 5 mL of fresh PBS at each time point. Method 2: Tubes corresponding to each sampling time were established at time zero, with each tube containing 3 carboplatin-impregnated CSH beads and 5 mL PBS. PBS was sampled from only the assigned tubes at each time point by evacuation of all 5 mL eluent. Control beads without carboplatin were also evaluated using both methods. Samples were analyzed for platinum concentration by ICP-MS.Results: Platinum was released from carboplatin-impregnated CSH beads for 22-30 days. There were significant differences in platinum concentrations and percentage of total incorporated platinum released over time and between methods.Conclusions and Clinical Relevance: Carboplatin-impregnated CSH beads eluted platinum for 22-30 days. Sampling method significantly affected platinum release from carboplatin-impregnated CSH beads at nearly all time points. Results from sampling Method 1 and Method 2 provide estimations of the minimum and maximum platinum concentrations expected to elute from carboplatin-impregnated CSH beads in vivo.