Computational consideration of cisplatin hydrolysis and acid dissociation in aqueous media: effect of total drug concentrations

Yotsuyanagi, Toshihisa; Usami, Masayuki; Noda, Yoichi; Nagata, Mariko

doi:10.1016/s0378-5173(02)00382-4

Cited by 32 publications

(34 citation statements)

References 23 publications

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“…At a chloride concentration of 110 mM, corresponding to a physiological extracellular chloride concentration, it has been calculated that 85% of the drug is present in the dichlorido form, with 11% in the chloridohydroxido form and 4% in the chloridoaqua form. [22][23][24] Thus, 96% of the drug would be expected to have an overall neutral charge at a chloride concentration of 110 mM. The neutral charge would facilitate diffusion of the drug through the nonpolar interior of the lipid bilayer.…”

Section: Kinetics Of Cisplatin Diffusion Across the Lipid Vesicle Memmentioning

confidence: 99%

Mechanisms of cell uptake and toxicity of the anticancer drug cisplatin

et al. 2014

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a Two major issues which hamper the use of the anticancer drug cisplatin are the development of cancer cell resistance and its nephrotoxicity. One possible mechanism by which resistance is reported to develop is a reduction in drug uptake across the cell membrane. While the passive uptake of cisplatin has long been cited as an important contribution, far greater attention has been given to active modes of uptake, particularly in recent research. Using unilamellar lipid vesicles together with the stopped-flow kinetic method we show here that the permeability coefficient of cisplatin increases significantly with the chloride concentration of the medium. This supports the hypothesis that cisplatin can enter cells via passive permeation through the lipid phase of the membrane, but becomes trapped within the cytoplasm because dissociation of chloride ligands yields a membrane-impermeant positively-charged aqua derivative. This is important evidence for a major role of passive membrane diffusion in the uptake of cisplatin, and suggests that reduced cell uptake is unlikely to be a significant mechanism leading to the development of drug resistance. Studies of rubidium ion uptake into the cytoplasm of Xenopus oocytes via the Na

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Section: Kinetics Of Cisplatin Diffusion Across the Lipid Vesicle Memmentioning

confidence: 99%

Mechanisms of cell uptake and toxicity of the anticancer drug cisplatin

et al. 2014

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“…According to previous studies (Yokoyama et al 1996;Yotsuyanagi et al 2002), the two chloride ligands are gradually substituted with H 2 O molecules in the presence of water. Both Pt(NH 3 ) 2 Cl(OH 2 ) + and Pt(NH 3 ) 2 Cl(OH 2 ) 2+ 2 can be formed by the aqueous complex based on the cisplatin dose used in this study.…”

Section: The Delivery Of Platinum Drugs From Thermosensitive Hydrogelmentioning

confidence: 99%

The Delivery of Platinum Drugs from Thermosensitive Hydrogels Containing Different Ratios of Chitosan

et al. 2008

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New thermosensitive hydrogels of poly(N-isopropylacrylamide) (PNIPAAm) with chitosan (CPN) were prepared and evaluated for use in the delivery of the platinum drugs, cisplatin and carboplatin. The effects of polymers containing different ratios of chitosan on the physicochemical and drug release characteristics were examined. The sol-gel transition temperature of the hydrogels was determined by differential scanning calorimetry (DSC) and viscometry. Discrepancies in the transition temperature among the various polymer systems were more pronounced when determined by viscosity compared by DSC, with the CPN showing a higher transition temperature than PNIPAAm. The cross-sectional structure and surface topography of the hydrogels were examined by scanning electronic microscopy (SEM) and atomic force microscopy (AFM), respectively. The incorporation of chitosan further increased the entanglement of the hydrogel network. An increase in the chitosan ratio in the polymers (CPN-H) also increased the cross-linking structure. A smoother surface of hydrogel matrices was observed for CPN compared with PNIPAAm. All hydrogels tested significantly reduced drug release compared with an aqueous solution. The release rate of platinum drugs from PNIPAAm was retarded at the late stage. CPN matrices could continuously deliver platinum drugs during the experiment. The rate of release from CPN-H was generally slower than that from hydrogels and had a lower chitosan ratio (CPN-L), presumably due to the more-tortuous pathways in the hydrogels. Thermosensitive hydrogels like those prepared in

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“…Burroug ei ul I Journol of Ortliopuctlic ReseLircli 22 (2004) [703][704][705][706][707][708] reactive toward the apatite surface. The formation of Ptphosphate complexes and a number of other cisplatin derivatives depending on chloride and drug concentrations has also been reported [15,25]. Due to the complexity of cisplatin solution chemistry it is possible that several Pt complexes may have formed during binding to CaP or form during drug release.…”

mentioning

confidence: 99%

Interactions of cisplatin with calcium phosphate nanoparticles: In vitro controlled adsorption and release

Barroug

Kuhn

Gerstenfeld

et al. 2004

Journal Orthopaedic Research

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A new system for the local delivery of chemotherapy to malignant solid tumors has been developed based on calcium phosphate (Cap) nanoparticles. The adsorption of the anti-neoplastic drug cis-diamminedichloroplatinum (cisplatin) was characterized on three types of apatitic CaP (poorly and well crystallized hydroxyapatite, and carbonated apatite). Adsorption isotherms obtained in chloride-free phosphate solutions at pH = 7.4 (24 and 37 "C) indicate that cisplatin adsorption increases with temperature and increases with decreasing crystallinity. Release studies in phosphate buffer saline (containing the chloride ion essential for release)showed that while the cumulative amount of released drug was the same for all apatites at 20 days (-70'%1 of the total bound), the least crystalline material released the drug more slowly. The drug release rate increased slightly with temperature. Cytotoxicity testing was conducted in a K8 clonal murine osteosarcoma cell line to verify that drug activity was retained after adsorption onto the apatite crystals. K8 cells were plated onto dried films of the apatitekisplatin conjugates and after 24 h, viability was measured with tritiated uridine. The apatitekisplatin formulations exhibited cytotoxic effects with a dose dependent diminishment of cell viability.

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Computational consideration of cisplatin hydrolysis and acid dissociation in aqueous media: effect of total drug concentrations

Cited by 32 publications

References 23 publications

Mechanisms of cell uptake and toxicity of the anticancer drug cisplatin

Mechanisms of cell uptake and toxicity of the anticancer drug cisplatin

The Delivery of Platinum Drugs from Thermosensitive Hydrogels Containing Different Ratios of Chitosan

Interactions of cisplatin with calcium phosphate nanoparticles: In vitro controlled adsorption and release

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