A DRUG SYSTEM (PDH) FOR INTERVENTIONAL RADIOLOGY SYNTHESIS, PROPERTIES, AND EFFICACY

RATIONALE AND OBJECTIVES. The authors synthesized and tested a novel h ydrogel system proposed for use in extra- and intravascular radiologic interventions, such as chemoembolizations and embolizations, and as a vehicle for sustained drug release. MATERIALS. The material was speci fically designed to meet the prerequisites of biodegradation, biocompa tibility, low immunogenicity, low toxicity, and easy use. The material consists of a protein backbone cross-linked with activated bifunction al polyethyleneglycol (PEG) derivatives (PEG-derivatized hydrogel, [PD H]) to which are attached therapeutic (e.g., doxorubicin, a chemothera peutic agent = PDH-dx) or diagnostic labels (e.g. Gd-DTPA). RESULTS. P DH-dx effectively reduced the risk of local tumor recurrence in a rat model when implanted locally after surgical tumor removal. After admin istration, PDH is degraded by proteases released from macrophages; imp lantations of 1 mL samples into paraspinal muscles of rats were comple tely absorbed within 4 weeks and its constituents were metabolized. An tibody titers (total Ig response) against the PDH were not detectable 1 week after implantation, whereas protein control substances elicited a strong response. CONCLUSIONS. PDH and its derivatives are relativel y nontoxic, biodegradable materials for use in radiologic intervention s and as a vehicle for sustained drug release.