Reduction of vinblastine neurotoxicity in mice utilizing a collagen matrix carrier.
Vinblastine sulfate (VLB) suspended within a collagen matrix (CM) as a diffusion limiting drug delivery vehicle was examined in vitro, as well as in mouse subcutaneous and brain tumor models. Against RIF-1 and KHT subcutaneous tumors, there was enhancement of antitumor activity with intratumoral (i.t.) delivery of VLB when it was combined with CM and/or epinephrine (epi) provided as a vasoactive agent to limit diffusion of VLB away from the injection site. Furthermore, in pharmacokinetic studies an 3-fold enhancement of tumor exposure to drug (AUC) with the CM-formulation was observed relative to the administration of free VLB i.t. Craniotactic injection of VLB into mouse brain in doses from 0.2 to 2 mg/kg revealed that the CM association markedly reduced the acute toxicity of VLB in normal mouse brain. Furthermore, mice with stereotactically implanted KHT brain tumors treated with 0.2 mg/kg VLB in CM had less tumor present in the brain histologically compared to the free VLB and untreated control groups.
Section of Neurosurgery, Palo Alto Veterans Administration Medical Center, CA.
R
R
Sutton
N
N
Yu
E
E
Luck
D
D
Brown
F
F
Conley
D000818:Animals; D001921:Brain / Q000473:pathology; D003094:Collagen; D004058:Diffusion; D004337:Drug Carriers; D004837:Epinephrine / Q000494:pharmacology; D007267:Injections; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000473:pathology; D013238:Stereotaxic Techniques; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014747:Vinblastine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*
D004337:Drug Carriers; D014747:Vinblastine; D003094:Collagen; D004837:Epinephrine