• Title/Summary/Keyword: platinum complex

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Teratogenicity Study of SKI 2053R, a New Platinum Anticancer Agent, in Rabbits (새로운 백금착물 항암제 SKI 2053R의 토끼 최기형성시험)

  • 김종춘;김갑호;박종일;김형진;정문구
    • Biomolecules & Therapeutics
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    • v.7 no.3
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    • pp.292-299
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    • 1999
  • SKI 2053 R, cis-Malonato [(4R, 5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum(II), is a newly developed antitumor platinum complex derived from cisplatin. Preclinical studies suggest that it may have greater antitumor activity and lower toxicity than cisplatin. Effects of test agent on general toxicity of does and embryonic development of Fl fetuses were investigated in rabbits. Sixty eight New Zealand white rabbits were distributed among three treated groups and a control group. SKI 2053R was administered intravenously to pregnant rabbits from days 6 to 18 of gestation at dose levels of 0, 0.67, 2.0, or 6.0 mg/kg/day. The pregnant does were subjected to the caesarean section on day 28 of gestation. No treatment-related changes in clinical signs, body weight, food consumption, and necropsy findings were observed in all groups. Fl fetuses showed no changes related to the treatment of SKI 2053R, except that an increase in the incidence of skeletal variations were observed at 6.0 mg/kg. There were no signs of material toxicity or embryotoxicity at 0.67 and 2.0 mg/kg. The results show that the administration of 6.0 mg/kg SKI 2053R induces skeletal variations in fetuses and that the no observed adverse effect levels(NOAELS) of SKI 2053R are considered to be over 6.0 mg/kg for does and 2.0 mg/kg for Fl fetuses in rabbits.

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Acute toxicity of cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R) in rats and Mice (랫드와 마우스에서 cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R)의 급성독성에 관한 연구)

  • Kang, Kyung-Sun;Shin, Dong-Jin;Cho, Jae-Jin;Kim, Hyoung-Ook;Kim, Bae-Hwan;Lee, Yong-Soon
    • Toxicological Research
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    • v.8 no.2
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    • pp.205-216
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    • 1992
  • cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R), an antitumor platinum complex, was selected for clinical evaluation on the basis of its experimental antitumor and toxicologic profiles in preclinical studies. These studies were performed to obtain information on its toxic signs, orgnas which are mainly affected, and to estimate its lethality in mice and rats given SKI 2053R through two routes of administration. In male and female rats given a single intragastrical dose of SKI 2053R, we estimated that $LD_{50}$ values were over 3.00g/kg, respectively. In male and female mice given a signle intragastrical dose of SKI 2053R, we estimated that $LD_{50}$ values were 2.44g/kg and 1.59g/kg, respectively, In a single intraperitoneal dose of SKI 2053R, we determined that $LD_{50}$ values of male and female rats were 227mg/kg and 182mg/kg, and those of male and female mice were 198mg/kg and 207mg/kg, respectively. In gross and histopathological examinations on dead animals, we found that kidney and liver were mainly affected.

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Preparation and Characterization of Cisplatin-Incorporated Chitosan Hydrogels, Microparticles, and Nanoparticles

  • Cha, Ju-Eun;Lee, Won-Bum;Park, Chong-Rae;Cho, Yong-Woo;Ahn, Cheol-Hee;Kwon, Ick-Chan
    • Macromolecular Research
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    • v.14 no.5
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    • pp.573-578
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    • 2006
  • Three different, polymer-platinum conjugates (hydrogels, microparticles, and nanoparticles) were synthesized by complexation of cis-dichlorodiammineplatinum(II) (cisplatin) with partially succinylated glycol chitbsan (PSGC). Succinic anhydride was used as a linker to introduce cisplatin to glycol chitosan (GC). Succinylation of GC was investigated systematically as a function of the molar ratio of succinic anhydride to glucosamine, the methanol content in the reaction media, and the reaction temperature. By controlling the reaction conditions, water-soluble, partially water-soluble, and hydrogel-forming PSGCs were synthesized, and then conjugated with cisplatin. The complexation of cisplatin with water-soluble PSGC via a ligand exchange reaction of platinum from chloride to the carboxylates induced the formation of nano-sized aggregates in aqueous media. The hydrodynamic diameters of PSGC/cisplatin complex nano-aggregates, as determined by light scattering, were 180-300 nm and the critical aggregation concentrations (CACs), as determined by a fluorescence technique using pyrene as a probe, were $20-30{\mu}g/mL$. The conjugation of cisplatin with partially water-soluble PSGC, i.e., borderline between water-soluble and water-insoluble PSGC, produced micro-sized particles $<500{\mu}m$. Cisplatin-complexed PSGC hydrogels were prepared from water-insoluble PSGCs. All of the cisplatin-incorporated, polymer matrices released platinum in a sustained manner without any significant initial burst, suggesting that they may all be useful as slow release systems for cisplatin. The release rate of platinum increased with the morphology changes from hydrogel through microparticle to nanoparticle systems.

Preparation of Nano-sized Pt Powders by Solution-phase Reduction (액상환원법(液相還元法)에 의한 백금(白金) 나노분말(粉末) 제조(製造))

  • Kim, Chul-Joo;Yoon, Ho-Sung;Cho, Sung-Wook;Sohn, Jung-Soo
    • Resources Recycling
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    • v.16 no.5
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    • pp.36-40
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    • 2007
  • Platinum plays an important role in many applications because of its extraordinary physical and chemical properties. All these applications require the use of platinum in the finely divided state. Therefore the preparation of platinum nanoparticles by reducing platinum-surfactant salt with reducing agent in the solution was investigated in this study. The net interaction between C14TABr and $H_2[PtCl_6]$ in aqueous solution results in the formation of $[C14TA]_2[PtCl_6]$. The concentration of C14TABr and the concentration of $H_2[PtCl_6]$ has to be above cmc and 0.32 mM, respectively in order to obtain complex-micelle aggregation for mono dispersed Pt particles. Pt particle size increases with increasing $H_2[PtCl_6]$ and C14TABr concentration. And the shape of Pt particles was well controlled with increasing surfactant concentration.

Platinum-Catalyzed and Ion-Selective Polystyrene Fibrous Membrane by Electrospinning and In-Situ Metallization Techniques

  • Hong, Seung-Hee;Lee, Sun-Ae;Nam, Jae-Do;Lee, Young-Kwan;Kim, Tae-Sung;Won, Sung-Ho
    • Macromolecular Research
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    • v.16 no.3
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    • pp.204-211
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    • 2008
  • A platinum-catalyzed polyelectrolyte porous membrane was prepared by solid-state compression of electrospun polystyrene (PS) fibers and in-situ metallization of counter-balanced ionic metal sources on the polymer surface. Using this ion-exchange metal-polymer composite system, fiber entangled pores were formed in the interstitial space of the fibers, which were surrounded by sulfonic acid sites ($SO_3^-$) to give a cation-selective polyelectrolyte porous bed with an ion exchange capacity ($I_{EC}$) of 3.0 meq/g and an ionic conductivity of 0.09 S/cm. The Pt loading was estimated to be 16.32 wt% from the $SO_3^-$ ions on the surface of the sulfonated PS fibers, which interact with the cationic platinum complex, $Pt(NH_3)_4^{2+}$, at a ratio of 3:1 based on steric hindrance and the arrangement of interacting ions. This is in good agreement with the Pt loading of 15.82 wt% measured by inductively coupled plasma-optical emission spectroscopy (ICP-OES). The Pt-loaded sulfonated PS media showed an ionic conductivity of 0.32 S/cm. The in-situ metallized platinum provided a nano-sized and strongly-bound catalyst in robust porous media, which highlights its potential use in various electrochemical and catalytic systems.

Synthesis of Platinum Nanoparticles Using Electrostatic Stabilization and Cluster Duplication of Perfluorinated Ionomer

  • Lee, Pyoung-Chan;Kim, Dong-Ouk;Han, Tai-Hoon;Kang, Soo-Jung;Pu, Lyong-Sun;Nam, Jae-Do;Kim, Byung-Woo;Lee, Jun-Ho
    • Macromolecular Research
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    • v.17 no.3
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    • pp.187-191
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    • 2009
  • Platinum (Pt) nanoparticles were prepared by the liquid-phase reduction of tetraammineplatinum (II) chloride $([Pt(NH_3)_4]Cl_2)$ using Nafion as a stabilizer under various conditions of the Nation phase. This method is novel in its use of electrostatic interactions between the Pt complex ions and sulfonic groups in the hydrated Nation molecules. The synthesized Pt nanoparticles of the recast film system had a cubic shape. In the case of the Nation solution system, the Pt nanoparticles mainly had a spherical shape. The shapes and sizes of the Pt nanoparticles were strongly influenced by the Nation phase.