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AUR Memorial Award 1993. A drug system (PDH) for interventional radiology. Synthesis, properties, and efficacy
R Weissleder1, A Bogdanov, H Frank
1Department of Radiology, Massachusetts General Hospital, Boston 02114.
Rationale And Objectives:
The authors synthesized and tested a novel hydrogel 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 specifically designed to meet the prerequisites of biodegradation, biocompatibility, low immunogenicity, low toxicity, and easy use. The material consists of a protein backbone cross-linked with activated bifunctional polyethyleneglycol (PEG) derivatives (PEG-derivatized hydrogel, [PDH]) to which are attached therapeutic (e.g., doxorubicin, a chemotherapeutic agent = PDH-dx) or diagnostic labels (e.g. Gd-DTPA).
Results:
PDH-dx effectively reduced the risk of local tumor recurrence in a rat model when implanted locally after surgical tumor removal. After administration, PDH is degraded by proteases release from macrophages; implantations of 1 mL samples into paraspinal muscles of rats were completely absorbed within 4 weeks and its constituents were metabolized. Antibody 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 relatively nontoxic, biodegradable materials for use in radiologic interventions and as a vehicle for sustained drug release.