Abstract
Purpose. Delivery of chemotherapeutics using implantable,biodegradable polymers provides a potentially powerful method of treating braintumors. The present studies examined the ability of injectablemicrospheres, formulated to release carboplatin or BCNU for 2–3 weeks,to enhance survival in a rodent model of deep, inoperable glioma.
Methods. Rat glioma (RG2) cells were implanted into the striatum ofrats. In a first experiment, the tumors were allowed to grow for 3 days,followed by either no treatment, bolus chemotherapy (100 μg), orimplantation of microspheres containing 10, 50, or 100 μg ofcarboplatin. The microspheres were implanted, via hypodermic injection,directly into the center of the small, 3-day-old tumors. In a secondexperiment, tumors grew for 8 days prior to treatment with eithercarboplatin- or BCNU-loaded microspheres. The microspheres werethen injected either directly into the center of these larger tumors orinto three sites along the perimeter of the tumor. Separate sets ofanimals received bolus chemotherapy (100 μg) into either the tumorcenter or around the tumor perimeter.
Results. Injection of carboplatin-loaded microspheres into the centerof the small 3 day old, tumors produced dose-related increases insurvival. When injections of carboplatin- or BCNU-loadedmicrospheres were made into the center of the larger, 8-day-old tumors,survival was not enhanced. However, when the microspheres wereinjected along the perimeter of the larger tumors, sustained-releasechemotherapy did significantly prolong survival. Bolus chemotherapywas less effective than sustained release chemotherapy.
Conclusions. Together, these data: (1) demonstrate that sustaineddelivery of chemotherapy in or near the tumor site is superior toequipotent bolus doses in inoperable tumors, (2) demonstrate thatinjection of sustained release microspheres into the tissue surroundinga growing tumor may provide superior effects over injections directlyinto the tumor mass, and (3) suggest that this approach may providea useful means of selectively delivering chemotherapeutics to tumorsor portions of tumors that cannot otherwise be treated with conventionalsurgical approaches.
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Emerich, D.F., Winn, S.R., Snodgrass, P. et al. Injectable Chemotherapeutic Microspheres and Glioma II: Enhanced Survival Following Implantation into Deep Inoperable Tumors. Pharm Res 17, 776–781 (2000). https://doi.org/10.1023/A:1007591721877
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DOI: https://doi.org/10.1023/A:1007591721877