Drug retention following intravesical delivery of fluorouracil therapeutic adhesive in C3H mouse bladder.
We have developed a fibrinogen-based, sustained-retention drug delivery system, therapeutic adhesive (TA), for application to resected tumor beds to reduce local tumor recurrences. In this study we evaluated the feasibility, safety and retention of the TA formulated with 5-fluorouracil (5-FU TA) after intravesical administration in a mouse bladder model. Radiolabeled [14C]5-FU TA or [14C]5-FU solution was delivered intravesically to C3H/He female mice. After drug administration, retention of 14C in the bladder was quantified by storage-phosphor autoradiography. A 2.6-fold increase in retention was observed with 5-FU TA when compared with 5-FU solution. The AUC(2 min-5 h) for 5-FU TA was 685 nmol h/mm2 compared with 260 nmol h/mm3 for 5-FU solution. No signs of toxicity in the bladder tissue or treatment-associated adverse effects were observed in the mice.
Singh
S S
SS
Matrix Pharmaceutical, Inc., Fremont, CA 94555, USA.
Smith
K M
KM
Brown
D M
DM
D000283:Administration, Intravesical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics* / Q000633:toxicity; D019540:Area Under Curve; D001345:Autoradiography; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D005340:Fibrinogen; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000633:toxicity; D006207:Half-Life; D051379:Mice; D008809:Mice, Inbred C3H; D014014:Tissue Adhesives; D001743:Urinary Bladder / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D014014:Tissue Adhesives; D005340:Fibrinogen; D005472:Fluorouracil