Local, sustained-release chemotherapeutic delivery systems have been developed to decrease the incidence of systemic toxic effects of chemotherapeutic agents while optimizing regional control of nonresectable and incompletely or marginally resected tumors.1–10 However, many of these delivery systems are not commercially available, have resulted in unacceptable regional complications, or have resulted in minimal improvement in clinical outcome.5,8,10,11
Carboplatin-impregnated calcium sulfate hemihydrate beads are a commercially available delivery system for sustained release of the platinum-containing chemotherapeutic agent carboplatin. Calcium sulfate hemihydrate is a proven biodegradable carrier for drug release and causes minimal reaction in tissues.12–18 Studies19,20 have shown promising usefulness of cisplatin-impregnated and CI-CSH beads for treatment of various tumors in horses and soft tissue sarcomas in dogs with negligible local adverse effects, compared with other carriers. Previously, we have described the short-term elution characteristics of CI-CSH beads in an in vitro study.21
Elution is the practice of extracting one material from another by washing it with a solvent. Historically, this process has been used as an in vitro method to predict the effectiveness of antimicrobial-impregnated carriers for sustained release of drugs in infected wounds.15,18,22 Studies evaluating elution characteristics in vitro have most commonly used a sample collection method in which the entirety of the eluent solution is exchanged at each sample collection time.12,15,18,22–35
In humans, the skin and skeletal muscle contain approximately two-thirds of the extracellular fluid volume, combined. Available evidence suggests that interstitial fluid in healthy skin and skeletal muscle is completely exchanged every 24 to 48 hours.36 However, if the tissues are substantially disrupted by inflammation, neoplasia, fibrosis, or surgical intervention, the exchange of fluid is altered.37,38 It is likely that the most commonly used in vitro sample collection method does not adequately mimic the fluid dynamics of these altered in vivo conditions. To our knowledge, no elution studies have taken into account the differences in dynamics of fluid exchange between healthy and disrupted tissues.
The purpose of the study reported here was to characterize the long-term elution of platinum from CI-CSH beads by comparing 2 distinct methods of sample collection: 1 that mimics an environment with rapid and complete fluid exchange, and 1 that mimics an environment where no fluid exchange occurs. We hypothesized that eluent samples obtained by the 2 distinct methods would result in differences in eluent platinum concentrations. An additional objective was to use the platinum concentrations determined in this study to define the minimum and maximum concentrations of platinum that could be expected for elution from CI-CSH beads in any in vivo condition.
Results of this study were presented in part at the American College of Veterinary Surgeons Surgical Summit, Nashville, Tenn, October 2015.
Carboplatin-impregnated calcium sulfate hemihydrate
Half maximal inhibitory concentration
Matrix III carboplatin beads, Wedgewood Pharmacy, Swedesboro, NJ.
Bead mold, University of Vermont Instrumentation and Modeling Facility, Burlington, Vt.
Dextran sulfate, Royer Biomedical Inc, Frederick, Md.
Midwest Laboratories Inc, Omaha, Neb.
SPSS, version 23.0, SPSS Inc, Armonk, NY.
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