Purpose: DC Bead™ is successfully used for chemoembolization of various liver cancers. The purpose of this study was todetermine the loading capacity of the semi-synthetic topoisomerase-1 inhibitor topotecan into the DC Bead™ microspheres under static or agitated conditions and to assess the physicochemical stability over a period of 7 days.
Methods: Commercially available topotecan hydrochloride powder (Hycamtin®) was reconstituted with water for injection to yield a nominal concentration of 1 mg/mL topotecan. Polyvinyl alcohol (PVA)-based microspheres (DC Bead™, 300–500 µm, 2 mL/vial) were mixed with 4 mL of the reconstituted topotecan solution. Vials were stored light protected at room temperature under static or agitated conditions for 7 days (n = 3, for each loading condition). At different time intervals, samples were taken from the excess solution and assayed via a stability-indicating HPLC assay. Drug-loading profiles were determined by measuring the remaining topotecan concentration in the excess solution.
Results: Under agitated conditions, topotecan was loaded into the microspheres rapidly after mixing. After 5 min 86.4 ± 0.1% of topotecan was loaded. Under static conditions, drug uptake was slower. Only 65.0 ± 0% were loaded after 5 min; 86.6 ± 0.1% drug uptake was achieved not until 1 h. Over a storage period of 7 days, topotecan remained loaded in the DC Bead™ microspheres at a level of >90%.
Conclusion: Drug uptake of 4 mg topotecan (1 mg/mL solution) into DC Beads™ was faster under agitated loading conditions. Nevertheless, after 1 h, ∼90% of topotecan was loaded into the DC Bead™ microspheres independent from the type of loading condition. The loading rate remained >90% over the observation period of 7 days and light-protected storage at room temperature. Loading and stability of topotecan-loaded DC Beads™ is suitable and convenient for preparation in a pharmacy-based cytotoxic preparation unit.
VarelaMRealMIBurrelMFornerASalaMBrunetM. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol2007; 46(3): 474–481.
2.
LewisALGonzalezMVLeppardSWBrownJEStratfordPWPhillipsGJ. Doxorubicin eluting beads – 1: effects of drug loading on bead characteristics and drug distribution. J Mater Sci Mater Med2007; 18(9): 1691–1699.
3.
LewisALGonzalezMVLloydAWHallBTangYWillisSL. DC bead: in vitro characterization of a drug-delivery device for transarterial chemoembolization. J Vasc Interv Radiol2006; 17(2 Pt 1): 335–342.
ForsterRESmallSATangYHeaysmanCLLloydAWMacfarlaneW. Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer. JMater Sci Mater Med2010; 21(9): 2683–2690.
PizzolatoJFSaltzLB. The camptothecins. Lancet2003; 361(9376): 2235–2242.
8.
KrämerIThiesenJ. Stability of topotecan infusion solutions in polyvinylchloride bags and elastomeric portable infusion devices. J Oncol Pharm Pract1999; 5(2): 75–82.
9.
KaiserJThiesenJKrämerI. Stability of irinotecan-loaded drug eluting beads (DC Bead) used for transarterial chemoembolization. J Oncol Pharm Pract2010; 16(1): 53–61.
Biocompatibles UK. DC BeadTM – Drug Delivery Embolisation System – Instructions for use. 2005.
12.
CraigSBBhattUHPatelK. Stability and compatibility of topotecan hydrochloride for injection with common infusion solutions and containers. J Pharm Biomed Anal1997; 16(2): 199–205.
TaylorRRTangYGonzalezMVStratfordPWLewisAL. Irinotecan drug eluting beads for use in chemoembolisation: in vitro and in vivo evaluation ofdrug release properties. Eur J Pharm Sci2007; 30(1): 7–14.
