An in-vitro evaluation of three types of drug-eluting microspheres loaded with irinotecan.

To compare the mechanical and chemical properties of three commercially available microspheres loaded with irinotecan. LifePearl (200 µm), DC Bead (100-300 µm), and Tandem (100 µm) microspheres were loaded with irinotecan. For loading, elution, and stability determinations, irinotecan concentrations were quantified using validated high-performance liquid chromatography methods. In-vitro elution was performed over 24 h using a USP 4 dissolution apparatus. Diameter measurements were performed using light microscopy. Time in suspension was considered as the time required for the microspheres to vacate 1/3 of the volume. All three microsphere types rapidly loaded irinotecan, with more than 95% loading at 1 h. In-vitro elution of irinotecan was rapid for LifePearl and DC Bead microspheres, with more than 98% elution at 1 h, and delayed for Tandem microspheres, with about 70% elution at 6 h. After loading with irinotecan, the average diameter of LifePearl and DC Bead microspheres was reduced by 9 and 18%, respectively, and was unchanged for Tandem microspheres. All three microsphere types lost 4-6% of the loaded irinotecan almost immediately upon placement in contrast: water and contrast: 5% dextrose, but further losses were minimal over 2 weeks. LifePearl microspheres remained longer in suspension (392±23 s) compared with DC Bead (154±13 s, P<0.001) and Tandem (198±19 s, P<0.001) microspheres. All three microsphere types load irinotecan rapidly. LifePearl and DC Bead microspheres elute irinotecan rapidly. Elution is delayed with Tandem microspheres. LifePearl microspheres show the longest time in suspension.

An In Vitro Evaluation of Four Types of Drug-Eluting Microspheres Loaded with Doxorubicin.

PURPOSE: To compare in vitro properties of 4 drug-eluting embolic agents loaded with doxorubicin. MATERIALS AND METHODS: DC Bead (100-300 µm), LifePearl (200 µm), HepaSphere (30-60 µm), and Tandem (100 µm) microspheres were loaded with 40 mg/20 mL of doxorubicin per milliliter of microspheres. Loading, elution, diameter changes after loading, changes in the amount of doxorubicin loaded over 2 weeks in storage, and time in suspension were evaluated. RESULTS: All microspheres loaded > 99% doxorubicin within 1 hour. In vitro elution reached a plateau by 6 hours, with 30% ± 5, 21% ± 2, 8% ± 3, and 6% ± 0 of the loaded doxorubicin eluted for LifePearl, DC Bead, HepaSphere, and Tandem microspheres, respectively, with at least 1 statistically significant difference between at least 2 of the products in doxorubicin eluted at every time point. The times to elute 75% of the total released doxorubicin were 197, 139, 110, and 77 min for DC Bead, LifePearl, HepaSphere, and Tandem microspheres, respectively. The average diameters of LifePearl, DC Bead, and Tandem microspheres were reduced after loading by 24%, 20%, and 9%, respectively. After suspension in contrast medium, no changes were observed in doxorubicin loading over 2 wk. After loading, times in suspension were 8.4 min ± 0.2, 6.0 min ± 0.1, 3.1 min ± 0.2, and 2.9 min ± 0.3 for Tandem, LifePearl, DC Bead, and HepaSphere microspheres, respectively. CONCLUSIONS: Although drug-eluting embolic agents universally loaded doxorubicin within 1 hour, the elution amounts, rates of release, diameter shrinkage, and times in suspension varied by product.

Measuring dimethylallyl diphosphate available for isoprene synthesis.

Dimethylallyl diphosphate (DMADP) is a central metabolite in isoprenoid metabolism, but it is difficult to measure. Three different methods for measuring DMADP are compared, and a new method based on the conversion of DMADP to isoprene using recombinant isoprene synthase is introduced. Mass spectrometry is reliable but does not distinguish between DMADP and isopentenyl diphosphate. Acid hydrolysis is reliable for measuring DMADP in bacterial extracts but overestimates DMADP in plant samples. To measure the DMADP in chloroplasts, light minus dark measurements are normally used. Chloroplast DMADP amounts measured using acid hydrolysis and a mass spectrometric method were comparable in this assay. Post-illumination isoprene emission tended to slightly overestimate chloroplast DMADP concentration. The DMADP pool size in bacteria is highly regulated, consistent with previous observations made with plants. DMADP is a very labile metabolite, but four methods described here allow measurements of samples from plants and bacteria. The use of recombinant isoprene synthase can greatly simplify the analysis. The various techniques tested here have advantages and disadvantages, and it is useful to have more than one method available when studying biological isoprene production.