AUR Memorial Award 1993. A drug system (PDH) for interventional radiology. Synthesis, properties, and efficacy.
OBJECTIVE
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.


METHODS
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.
Weissleder
R
R
Department of Radiology, Massachusetts General Hospital, Boston 02114.
Bogdanov
A
A
Frank
H
H
Nossiff
N
N
Bogdanova
A
A
Schaffer
B K
BK
Brady
T
T
Wittenberg
J
J
D000818:Animals; D001673:Biodegradation, Environmental; D003432:Cross-Linking Reagents / Q000493:pharmacokinetics / Q000633:toxicity; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity; D016503:Drug Delivery Systems; D005782:Gels; D008279:Magnetic Resonance Imaging; D051379:Mice; D009132:Muscles / Q000187:drug effects / Q000473:pathology; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000633:toxicity; D015641:Radiography, Interventional; D051381:Rats; D011916:Rats, Inbred F344; D012235:Rhodamines / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003432:Cross-Linking Reagents; D005782:Gels; D012235:Rhodamines; D011092:Polyethylene Glycols; D004317:Doxorubicin