Antitumor activity of orally administered SMANCS, a polymer-conjugated protein drug, in mice bearing various murine tumors.
The antitumor activity of an oily formulation of SMANCS (oily SMANCS), which is a product of conjugation between a proteinaceous antitumor antibiotic neocarzinostatin and poly (styrene-co-maleic acid), after oral administration to mice inoculated with various murine tumors was investigated. BALB/c mice, inoculated either s.c. or i.p. with allogeneic (sarcoma-180) or syngeneic (RL male 1 leukemia and Meth A fibrosarcoma) tumors, were treated with oily SMANCS orally or with an aqueous formulation of SMANCS (aqueous SMANCS) i.v. or i.p. Oral administrations of oily SMANCS or i.v. administrations of aqueous SMANCS to mice bearing three types of tumors in the ascites form resulted in a weak inhibition of tumor growth as compared to the complete inhibition of these tumors by aqueous SMANCS administered i.p. In mice bearing solid tumors, tumor growth was inhibited by 63-82% when a 10 mg/kg dose of oily SMANCS was administered orally to these mice. The antitumor potential of oily SMANCS administered orally was comparable to that obtained from solid tumor-bearing mice receiving i.v. doses of aqueous SMANCS. These results suggest that the oral administration of oily SMANCS to mice bearing various solid tumors inhibits the tumor growth as effectively as aqueous SMANCS administered i.v.
Schmitt
D A
DA
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-0882.
Kisanuki
K
K
Kimura
S
S
Oka
K
K
Pollard
R B
RB
Maeda
H
H
Suzuki
F
F
D000284:Administration, Oral; D000818:Animals; D005354:Fibrosarcoma / Q000139:chemically induced / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008297:Male; D008299:Maleic Anhydrides / Q000008:administration & dosage / Q000627:therapeutic use*; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D011137:Polystyrenes / Q000008:administration & dosage / Q000627:therapeutic use*; D012510:Sarcoma 180 / Q000188:drug therapy*; D013997:Time Factors; D009353:Zinostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D008299:Maleic Anhydrides; D011137:Polystyrenes; C035755:poly(maleic acid-styrene)neocarzinostatin; D008748:Methylcholanthrene; D009353:Zinostatin