Free Platinum Research Articles

Quantifying platinum binding on protein-functionalized magnetic microparticles using single particle-ICP-TOF-MS.

This work describes an analytical procedure, single particle-inductively coupled plasma-time-of-flight-mass spectrometry (SP-ICP-TOF-MS), that was developed to determine the platinum binding efficiency of protein-coated magnetic microparticles. SP-ICP-TOF-MS is advantageous due to its ability to quasi-simultaneously detect all nuclides (7Li-242Pu), allowing for both platinum and iron (composition of magnetic microparticles) to be measured concurrently. This method subsequently allows for the differentiation between bound and unbound platinum. The 1 μm magnetic microparticles were fully characterized for their iron concentration, particle concentration, and trace element composition by bulk digestion-ICP-MS and SP-ICP-TOF-MS. The results of both approaches agreed with the certificate values. Using the single particle methodology the platinum loading was quantified to be to 0.18 ± 0.02 fg per particle and 0.32 ± 0.02 fg per particle, for the streptavidin-coated and azurin-coated microparticles, respectively. Both streptavidin-coated and the azurin-coated microparticles had a particle-platinum association of >65%. Platinum bound samples were also analyzed via bulk digestion-based ICP-MS. The bulk ICP-MS results overestimated platinum loading due to free platinum in the samples. This highlights the importance of single particle analysis for a closer inspection of platinum binding performance. The SP-ICP-TOF-MS approach offers advantages over typical bulk digestion methods by eliminating laborious sample preparation, enabling differentiation between bound/unbound platinum in a solution, and quantification of platinum on a particle-by-particle basis. The procedure presented here enables quantification of metal content per particle, which could be broadly implemented for other single particle applications.

Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines.

The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin include drug resistance and significant side effects. Due to their better stability, as well as the possibility to introduce biologically active ligands in their axial positions constructing multifunctional prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations. Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV) conjugates demonstrated higher or comparable activity with respect to cisplatin against different human breast cancer cell lines, while upon immobilization, superior antiproliferative activity with markedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin was observed. Mechanistic investigations with the most potent conjugate, cisplatin-diacetyl caffeate (1), and the corresponding MSNs (SBA-15|1) in a 4T1 mouse breast cancer cell line showed that these compounds induce apoptotic cell death causing strong caspase activation. In vivo, in BALB/c mice, 1 and SBA-15|1 inhibited the tumor growth while decreasing the necrotic area and lowering the mitotic rate.

Nickel sulphide-reduced graphene oxide composites as counter electrode for dye-sensitized solar cells: Influence of nickel chloride concentration

Nickel sulphide-reduced graphene oxide (NiS-rGO) composite films have been prepared via modified Hummers’s method assisted with spin coating technique. The NiS-rGO samples were then employed as counter electrode in a dye-sensitized solar cell (DSSC). The main aim of this work is to investigate the relationship between the concentrations of NiCl2 with the properties of NiS-rGO and performance parameters of the device. The dominant rGO and minor NiS phase exist in the composite. The morphology of the composite is white strips rGO and NiS agglomerate particle. The element of C, O, Ni and S present in the composite. The highest η of 1.04% and Jsc of 7.39 mA cm−2 were obtained from the device with 0.06 M NiCl2 resulted from the longest carrier lifetime. The photovoltaic parameters results reveal that NiS-rGO composite has potential to become as a free platinum counter electrode of DSSC.

Dose-escalation of oxaliplatin in hemodialysis patient treated with FOLFOX therapy

Rationale:Oxaliplatin is a key part of the standard treatment for colorectal cancer which is formally contraindicated in patients with severe renal dysfunction. Here, we investigated a safe and efficient dosing schedule of oxaliplatin in folinic acid, fluorouracil, and oxaliplatin (FOLFOX) regimen by monitoring total and free platinum concentrations in plasma.Patient concerns:A 47-year-old female with chronic hemodialysis was diagnosed with left-sided colon cancer and underwent colectomy. One year later, she was presented with omentum metastasis and needed further treatment.Diagnoses:The computed tomography (CT) scanning revealed multiple omental nodules. Positron emission tomography-CT (PET-CT) showed increased uptake of the nodules.Interventions:The patient was treated with FOLFOX therapy every 3 weeks. The oxaliplatin began with 50 mg/m2 and gradually increased 85 mg/m2 as in the standard regimen. A 4-hour dialysis was started 1 hour after the end of oxaliplatin infusion.Outcomes:The free platinum concentration time curve showed a biomodel pattern. The Cmax of the 1st peak we observed in our patients at the standard dose is comparable to patients with normal renal function. This patient was treated with FOLFOX for 12 courses. No apparent adverse effect was observed during the treatment.Lessons:The FOLFOX can be safely administered in hemodialysis patients on a long-term basis. Dose reduction of oxaliplatin is not necessarily needed if hemodialysis is performed soon after the infusion. Further studies are needed to distinguish between active and inactive oxaliplatin products during the 2nd peak of the free platinum concentration curve in this population.

Atomic Structure and Dynamics of Epitaxial Platinum Bilayers on Graphene.

Platinum atomic layers grown on graphene were investigated by atomic resolution transmission electron microscopy (TEM). These TEM images reveal the epitaxial relationship between the atomically thin platinum layers and graphene, with two optimal epitaxies observed. The energetics of these epitaxies influences the grain structure of the platinum film, facilitating grain growth via in-plane rotation and assimilation of neighbor grains, rather than grain coarsening from the movement of grain boundaries. This growth process was enabled due to the availability of several possible low-energy intermediate states for the rotating grains, the Pt-Gr epitaxies, which are minima in surface energy, and coincident site lattice grain boundaries, which are minima in grain boundary energy. Density functional theory calculations reveal a complex interplay of considerations for minimizing the platinum grain energy, with free platinum edges also having an effect on the relative energetics. We thus find that the platinum atomic layer grains undergo significant reorientation to minimize interface energy (via epitaxy), grain boundary energy (via low-energy orientations), and free edge energy. These results will be important for the design of two-dimensional graphene-supported platinum catalysts and obtaining large-area uniform platinum atomic layer films and also provide fundamental experimental insight into the growth of heteroepitaxial thin films.

A retrospective review on extended carboplatin infusion and incidence of hypersensitivity reaction in gynecologic malignancies in a single institution.

e17102 Background: Carboplatin has been the standard treatment for advanced gynecologic malignancies in the first line setting as well as treatment of relapsed disease. Carboplatin induced hypersensitivity reaction (HSR) is observed more frequently in a second line setting and symptoms can range from rash to life threatening symptoms such as anaphylaxis, which could preclude further treatment. A retrospective study by O’Cearbhaill showed HSR rate with extended infusion protocol to be 3.4%. However, two subsequent prospective studies by Lax and O’Cearbhaill did not find that extended infusion reduced the risk or severity of HSR. We reviewed the incidence of HSR with three hour extended-infusion carboplatin at our institution. Methods: Our practice at the Monter Cancer Center changed from standard 1 hour carboplatin retreatment infusion to extended-infusion in 2011. We reviewed charts of 162 patients from 2011 to present who received a three hour extended infusion of carboplatin. All patients received prophylactic H1 and H2 blockers along with steroids. HSR was determined in two ways: 1) Identifying patients who reported clinical symptoms of HSR. 2) Identifying which patients had received diphenhydramine, hydrocortisone and/or epinephrine as indicated for an infusion reaction. Results: 162 patients were identified: 83 with ovarian cancer, 44 with uterine cancer, and 16 with fallopian tube cancer, 10 with primary peritoneal cancer, and 9 with cervical/vulvar cancer. Most had relapsed disease and were previously treated for stage IV (35%), or stage III (47%) with platinum doublet chemotherapy at least six months prior. Only 1 out of 162 (0.6%) had a grade 1 reaction with hives and was treated with dexamethasone and diphenhydramine. She was previously treated with carboplatin 17 months prior. Her current HSR occurred during her fifth cycle of retreatment. She was not re challenged with the drug and elected not to undergo desensitization. Conclusions: Hypersensitivity reactions develop in about 12-33% of women retreated with carboplatin peaking at eight cycles (Lax et al.). The mechanism behind HSR is unclear but considered to be from repeated exposure to free platinum metal concentration. Incidence of HSR at our institution was lowest ever-reported at 0.6%, suggesting that our extended infusion protocol with the appropriate premedication is appropriate for carboplatin-retreat patients. Further prospective studies to evaluate this regimen is warranted.

Chlorate Electrochemical Removal from Aqueous Media Based on a Possible Autocatalytic Mechanism

The electrochemical chlorate reduction at the Pt electrode in 0.5 M H2SO4 deaerated solutions has been studied using potentiostatic steady-state voltammetry. The kinetics parameters (Tafel slope, charge transfer coefficient, current density, and reaction order) were evaluated in function of chlorate concentration (1x10-4 � 0.2 M KClO3). The process of chlorate reduction is a complex one that implies two charge transfer controlled steps with formation of free radicals and an extent potential region controlled by the concentration polarization. The current density dependence of chlorate concentration tends to an exponential growth at concentration � 0.1 M KClO3 and becomes exponential in the conditions of the catalyst system presence. In the second charge transfer, a surface reaction between free radical �Cl-2 and platinum electrode with formation of complex anions PtCL42- and PtCL62- is responsible for the rapid increase of the reaction rate.

High Efficiency CeO₂/CNTs Modified Pt/CNTs Catalysts for Electrochemical Oxidation of Methanol.

The composite catalysts of CeO2/multi-walled carbon nanotubes (CNTs)-Pt/CNTs were prepared. Morphologies of the resulting catalysts were characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD) techniques. The results indicated that most of particles have a narrow particle size distribution, and the size distribution followed the Gaussian distribution. The electro-catalytic activity of the CeO2 or CeO2/CNTs modified Pt/CNTs catalysts towards the methanol oxidation reaction was examined by using the cyclic voltammetry (CV) experiments in H2SO4 containing methanol electrolyte. It is found that both catalysts of CeO2-Pt/CNTs and CeO2/CNTs-Pt/CNTs exhibited significantly improved electrochemically active surface area (EAS) and high catalytic activity toward methanol electro-oxidation, as compared with Pt/CNTs. Furthermore, the corresponding CO-stripping test showed that the onset potential and peak maxima in ceria incorporated platinum catalyst were shifted to lower potentials compared to that of the ceria free platinum system. The effects of the loading of CeO2 on CNTs on the electrocatalytic activity of the composite catalysts for methanol oxidation were investigated. We found that the optimal value of ceria loading on CNTs occurred at 40%.

Abstract A095: Phase Ib study of anetumab ravtansine in combination with pemetrexed and cisplatin in patients with mesothelin-expressing epithelial mesothelioma or nonsquamous non-small cell lung cancer

Abstract Background: Phase I study with the antibody-drug conjugate anetumab ravtansine demonstrated promising safety and efficacy as monotherapy in mesothelin-expressing tumors, and in particular for patients with advanced metastatic malignant pleural mesothelioma. Pemetrexed in combination with cisplatin is standard for first-line treatment of patients with metastatic mesothelioma and NSCLC. We therefore conducted a phase Ib study to determine the safety, tolerability, and maximum tolerated dose (MTD) of anetumab ravtansine in combination with pemetrexed/cisplatin (Pem/Cis) in subjects with mesothelin-expressing predominantly epithelial mesothelioma or nonsquamous NSCLC. Methods: Patients with histologically confirmed, unresectable, locally advanced or metastatic, mesothelin-expressing predominantly epithelial pleural or peritoneal mesothelioma or nonsquamous NSCLC, who previously failed ≤3 prior lines of chemotherapy, were eligible. Patients were prescreened based on obligatory tumor staining for mesothelin as determined by the Ventana MSLN (SP74) immunohistochemistry assay. Anetumab ravtansine was administered by 1-hour IV infusion on day 1 of every 21-day treatment cycle (Q3W). Pem (500 mg/m2) and Cis (75 mg/m2) were administered as IV infusions Q3W. Serial plasma samples were collected and analyzed for anetumab ravtansine and its components, pemetrexed, total and free platinum. Response to therapy was assessed by RECIST 1.1 and modified RECIST criteria for mesothelioma. Results: As of June 12, 2017, 17 patients had been treated and had received ≥2 cycles of treatment, including 7 patients with pleural mesothelioma, 9 with peritoneal mesothelioma, and 1 with NSCLC. Three patients were treated with anetumab ravtansine 5.5 mg/kg in combination with Pem/Cis with no dose-limiting toxicity (DLT). Six patients were then treated with anetumab ravtansine 6.5 mg/kg in combination with Pem/Cis, again without DLTs. This dose in combination was deemed as the MTD. An additional 8 patients were enrolled in an MTD expansion cohort. Anetumab ravtansine-related adverse events were mainly grade (G)1 and G2. G1/G2 eye toxicities were possibly more frequent with the combination than in historical data. There was one G3 corneal microcystic event and one G3 hypertension. There was a 50% overall response rate (all partial responses) from 16 evaluable patients. Of 13 patients treated at the 6.5 mg/kg MTD dose of anetumab ravtansine in combination with Pem/Cis, the overall response rate was 46%. Based on comparisons to historical data and within-subject comparisons in small number of subjects, clinically relevant PK interaction was not observed. Conclusions: Anetumab ravtansine at 6.5 mg/kg dosed Q3W in combination with standard dosing of Pem/Cis had a manageable toxicity profile without evidence of PK interaction and with early signs of clinical efficacy. Anetumab ravtansine at 6.5 mg/kg in combination with Pem 500 mg/m2 and Cis 75 mg/m2, all administered in a Q3W regimen, is thus feasible and the recommended dose for future study. Citation Format: Raffit Hassan, Ding Wang, John Wrangle, Anish Thomas, Angus Byars, Lianne Asschert, Rolando Atienza, Prabhu Rajagopalan, Annette Walter, Jun Zhang, Nenad Sarapa, Hedy Kindler. Phase Ib study of anetumab ravtansine in combination with pemetrexed and cisplatin in patients with mesothelin-expressing epithelial mesothelioma or nonsquamous non-small cell lung cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A095.

Binder free platinum nanoparticles decorated graphene-polyaniline composite film for high performance supercapacitor application

Conventional supercapacitors use insulating binders with active materials for fabricating working electrodes. Use of such binder reduces electrical conductivity of the electrode, thus causing energy wastage of supercapacitor. To overcome this, herein, we report binder free Platinum (Pt) nanoparticles (NPs) decorated Graphene–Polyaniline (Gr-PANi) composite modified electrode for supercapacitor application. Pt decorated Gr-PANi composite was prepared by template-free electrochemical polymerization method followed by electro-deposition of Pt NPs. Detailed structural and chemical characterization of the composite were done by SEM, EDX spectroscopy and Raman scattering. FESEM image of Pt decorated Gr-PANi composite revealed nano-fibrous structure of PANi (average diameter of 50–100nm) with Pt NPs uniformly deposited on its surface. Interconnected network of PANi nanofibers made matrix highly porous, thereby, providing an improved electrode/electrolyte interface area and shorter diffusion lengths for electrolytic ions. The electrochemical behavior of Pt NPs decorated Gr-PANi composite film was studied by cyclic voltammetry while galvanostatic charge–discharge measurements were carried out to investigate its capacitive performances. Pt decorated Gr-PANi composite based supercapacitor exhibited higher specific capacitance of 922.5F/g which was∼1.75 folds greater than that of only Gr-PANi based electrode at same current density (1A/g) and much higher than previously reported Gr-PANi composite based supercapacitors. The developed Pt decorated Gr-PANi composite modified electrode exhibited charge capacity of 0.57 mAh/cm2 and discharge capacity of 0.29 mAh/cm2 which were 2.4 folds and 1.81 folds higher than only Gr-PANi electrode respectively. The significant improvement in specific capacitance with excellent sustainability to higher current, superior rate capability, charge storage capacity and cycling stability can be attributed to the synergistic effect of electrical double-layer capacitance and pseudocapacitance resulting from Gr and PANi respectively and excellent catalytic ability of Pt NPs. The as-synthesized Pt decorated Gr-PANi composite offers simple, promising and binder free electrode material for energy storage devices.

Pharmacokinetic evaluation of intrapleural perfusion with hyperthermic chemotherapy using cisplatin in patients with malignant pleural effusion

ObjectivesMalignant pleural effusion (MPE) has a poor prognosis. Most patients are treated with tube thoracostomy and sclerotherapy, although its success rate is around 64%. We have investigated intrapleural perfusion with hyperthermic chemotherapy (IPHC) using cisplatin in a study with a pharmacokinetic evaluation. MethodsPatients with MPE, performance status of 0–1, possibility of good lung expansion and Cr<1.2mg/dL were treated with IPHC. The circuit was filled with 2000mL of normal saline containing cisplatin at a dose of 80mg/m2. Under video-assisted thoracoscopic surgery, the thoracic cavity was filled and perfused at a speed of approximately 1L/min at a temperature of 43°C for 1h. Perfusion solution and plasma samples were periodically collected, and concentrations of protein-unbound (free) platinum, which was the active derivative of cisplatin, and total platinum were determined by flameless atomic absorption spectrometry. ResultsTwenty patients with MPE (8 lung cancers, 7 mesotheliomas, and 5 others) were enrolled in this study. Rate of free platinum concentration relative to total platinum concentration in perfusion solution after 1hr IPHC at 43°C was 61.1±12.9%. Area under curve (AUC) of free platinum in the pleural space was calculated to be 26.3μg/mLxh, resulting in complete control of pleural effusion for 3 months after IHPC in all cases (95% confidence interval: 83–100%). While, absorption rate of total platinum from the pleural space was 33.8±17.0% (27.4±13.6mg/m2), and the maximum concentration of total platinum in serum was low, 0.66±0.31μg/mL, resulting in controllable side effects; grade 1 renal toxicity: 6 patients, grade 1 emesis: 7 patients. ConclusionsIPHC with cisplatin showed favorable pharmacokinetic profiles for an optional treatment to control malignant pleural effusion.

Surfactant free platinum nanocluster as fluorescent probe for the selective detection of Fe (III) ions in aqueous medium

We report the utilisation of platinum nanocluster (Pt NC) as a fluorescent sensor. The sensor displays an excellent selectivity and sensitivity towards Fe (III) ions in aqueous solution. The possible mechanism for the sensing was analyzed by photophysical studies and the results showed that the quenching of the NC by Fe3+ follow predominantly a static mechanism. The change in luminescent property occurs due to the specific interaction of the NCs and Fe3+ ions. We have also shown that this Pt NC can be utilized for the detection of Fe3+ in the human blood sample.

Low‐Generation Polyamidoamine Dendrimers as Drug Carriers for Platinum(IV) Complexes

An unsymmetrically carboxylated platinum(IV) analogue of oxaliplatin was coupled to low‐generation polyamidoamine dendrimers (PAMAM) with amino‐terminated surfaces [generations two (G‐2) and four (G‐4)]. 1D and 2D diffusion NMR spectroscopy and high‐resolution HPLC–MS/MS were used to characterise the platinum complexes and drug–dendrimer conjugates. The average loads of platinum(IV) complex per dendrimer were determined by inductively coupled plasma MS (ICP‐MS), and maximum loads of 38 % (six platinum units per dendrimer molecule) for the smaller G‐2 and 34 % (22 platinum units per dendrimer molecule) for G‐4 were obtained. As a result of this loading, the average diameters increased from 26 to 34 Å (30 %, G‐2) and from 46 to 63 Å (38 %, G‐4). The in vitro cytotoxicities of the free platinum(IV) complex, the complex‐loaded dendrimers and the free PAMAM analogues G‐2 and G‐4 were evaluated in the cisplatin‐sensitive ovarian cell line CH1/PA1 as well as in rather cisplatin‐insensitive colon (SW480) and lung (A549) carcinoma cells by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays. Although the free platinum(IV) compound displayed a rather moderate activity, the drug–dendrimer complexes showed load‐ and size‐dependent behaviour with IC50 values down to the low‐nanomolar range. In the cisplatin‐insensitive cell lines, the benefit of this platinum load primarily consists of added cytostatic rather than cytocidal effects, on the basis of the results from annexin V/PI (PI = propidium iodide) assays for apoptosis/necrosis induction.

Pharmacokinetic analyses of carboplatin in a patient with cancer of the fallopian tubes undergoing hemodialysis: A case report.

Opportunities for patients undergoing hemodialysis to receive chemotherapy are increasing. A combination of paclitaxel and carboplatin (TC) is first-line chemotherapy in patients with Müllerian cancer. However, the optimal dose and time interval between the end of carboplatin administration and initiation of hemodialysis remains to be elucidated. TC was administered to a patient with fallopian tube cancer undergoing hemodialysis. The paclitaxel regimen was determined to be 135 mg/m2 (total of 210 mg) over 3 h. After paclitaxel administration, 125 mg of carboplatin was administered over 1 h to achieve a target area under the concentration-time curve (AUC) of 5.0 mg•min/ml using the Calvert formula. The time interval between the end of carboplatin administration and hemodialysis initiation was 1 h at the first cycle, 16 h at the second cycle and 20 h at the third cycle, and the AUC obtained was 2.86, 4.16 and 6.0 mg•min/ml, respectively. The desired AUC of free platinum was demonstrated and only mild side effects were observed at the third cycle. Therefore, hemodialysis was initiated 20 h after completion of carboplatin infusion at cycles 4-6. The total chemotherapy planned was completed without severe adverse events. Measurement of the concentration of free platinum subsequent to administration is useful for determination of the optimal dose of carboplatin and time interval following administration to obtain an adequate AUC. The present study suggests that carboplatin can be administered to a patient undergoing hemodialysis, and that an adequate interval between the end of carboplatin administration and hemodialysis initiation may be ~20 h.

Oxaliplatin Pharmacokinetics and Pharmacodynamics in Three Metastatic Colorectal Cancer Patients with Hemodialysis

Aim: We investigated the safety and feasibility of L-OHP with chronic renal failure (CRF) on hemodialysis (HD) patients by examining the influence of pharmacokinetics and pharmacodynamics of oxaliplatin (L-OHP). Furthermore, we investigated. Methods: We present the results of three patients who were treated with modified FOLFOX6 (mFOLFOX6) chemotherapy for a mCRC with chronic renal failure on HD. We measured their plasma concentration of total platinum and free platinum. We evaluated whether L-OHP dose could be safely used for these patients. Different starting dose of L-OHP and 5-fluorouracil (50% and 75%) were used in these patients. Pharmacokinetics monitoring of platinum in plasma, plasma ultrafiltrates were measured these time schedule follow as: pre-chemotherapy infusion and 4 hours (pre-HD), 6 hours (half of HD), 8 hours (post HD), 48 hours after. Results: The 50% of peak concentrations (Cmax) was 0.27 μg・hr/mL ± 0.02 μg/mL and 75% Cmax was 0.41 μg・hr/mL ± 0.02 μg/mL. 50% of the area under the concentration versus time curve (AUC) was 14.8 μg・hr/mL ± 1.22 μg・hr/mL and 75% AUC was 22.43 μg・hr/mL ± 0.85 μg・hr/mL. Conclusion: We recognized these free plasma concentration which 50% dose of L-OHP was similar AUC between healthy and CRF patients. L-OHP pharmacokinetics and pharmacodynamics are altered in patients with CRF, but corresponding increase in L-OHP related hematological and non-hematological toxicities is not observed. It is important for cancer patients with CRF that the feasibility and efficacy of L-OHP combined chemotherapy should be determined.

Hepatotoxicity and pharmacokinetics of cisplatin in combination therapy with a traditional Chinese medicine compound of Zengmian Yiliu granules in ICR mice and SKOV-3-bearing nude mice.

BackgroundCisplatin (CDDP) is a highly effective chemotherapeutic agent used for therapy of many tumors and has been limited by its toxicity. Zengmian Yiliu granule (ZMYL), a compound preparation of traditional Chinese medicines, has been used in clinic as a complementary and alternative medicine for attenuating CDDP-induced toxicities and enhancing the tumor therapeutic effect of CDDP. The aim of the present study is to investigate hepaprotective effect of ZMYL against CDDP-induced hepatotoxicity. Further, the pharmacokinetic characteristics of CDDP in SKOV-3-bearing nude mice were observed.MethodsThe ICR mice were dosed orally with ZMYL for 7 days and then CDDP was injected intraperitoneally at a dose of 45 mg/kg body weight. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to evaluate the liver function. The total glutathione (T-GSH), reduced glutathione (GSH) and glutathione S-transferase (GST) levels were determined to evaluate the oxidant damage in liver homogenates. Tissue pathological change in liver was conducted by light microscopy analysis. The pharmacokinetic and tissue distribution of free and total platinum (Pt) after dosing of CDDP alone and combination with ZMYL were determined in SKOV-3-bearing nude mice by ICP-MS.ResultsOral administration of ZMYL prior to the CDDP treatment could prevent the CDDP-induced in lifting of ALT and AST, reduction of T-GSH, R-GSH and GST, and some histopathological alterations in ICR mice. Some differences in pharmacokinetic parameters between the two groups have been observed in higher CL and decreased MRT of free platinum (Pt) in plasma and total Pt in spleen in CDDP co-administration with ZMYL group. It indicated CDDP was cleared more quickly from blood and spleen, and could reduce the accumulation and toxic possibility of CDDP in combination with ZMYL.ConclusionsZMYL could be used as a beneficial supplement, which could attenuate CDDP-induced hepatotoxicity during CDDP chemotherapy and did not disturb the pharmacokinetics fate of CDDP significantly.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-015-0799-9) contains supplementary material, which is available to authorized users.

Cerium Tetrafluoride: Sublimation, Thermolysis, and Atomic Fluorine Migration.

Saturated vapor pressure p° and enthalpy of sublimation (ΔsH°) of cerium tetrafluoride CeF4 were determined by means of Knudsen effusion mass spectrometry in the range of 750-920 K. It was discovered that sublimation of cerium tetrafluoride from a platinum effusion cell competes with thermal decomposition to CeF3 in the solid phase, but no accompanying release of fluorine to the gas phase occurs. Thus, fluorine atoms migrate within the surface layer of CeF4(s) to the regions of their irreversible drain. We used scanning electron microscopy to study the distribution of the residual CeF3(s) across the inner surface of the effusion cell after complete evaporation of CeF4(s). It was observed that CeF3 accumulates near the edge of the effusion orifice and near the junction of the lid and the body of the cell, that is, in those regions where the fluorine atoms can migrate to a free platinum surface and thus be depleted from the system. Distribution of CeF3(s) solid particles indicates the ways of fluorine atoms migration providing CeF3(s) formation inside the CeF4(s) surface layer.

In vivo pharmacokinetic and tissue distribution investigation of sustained-release cisplatin implants in the normal esophageal submucosa of 12 beagle dogs.

The aim of this study was to clarify the pharmacokinetic, tissue distribution, hematologic, and histopathologic characteristics of sustained-release cisplatin from implants [CDDP-nanoparticle (NP) implants]. Eighteen dogs (six hybrids and twelve beagles) were divided into three groups. In Group A, the six hybrid dogs were intravenously administered 20 mg CDDP via a hind limb vein. In Groups B and C, CDDP-NP implants containing CDDP doses of 40 and 60 mg, respectively, were embedded into the esophageal submucosa of beagles via painless gastroscopy with an endoscopic booster. Graphite frameless atomic absorption spectrophotometry was used to measure total platinum in plasma and tissues at various timepoints. In addition, free platinum levels in Group B were determined using inductively coupled plasma mass spectrometry. Toxicologic evaluation was also conducted. Pharmacokinetic results indicated that the CDDP-NP implant could achieve a smooth pharmacokinetic curve, with the plasma invalid concentration reached after almost 480 h, which is approximately ten times longer than that of standard CDDP (48 h). The peak time, peak concentration, clearance, elimination half-life, area under the curve, volume of distribution at steady state, and mean residence time of Groups B and C were 494 and 211, 0.39 and 0.42, 0.044 and 0.059, 80.11 and 87.70, 44 and 49, 38.8 and 57.9, and 12.29 and 12.39 times those of Group A, respectively (all P < 0.05). The ratio of free/total platinum concentration was 2.0-3.1% in plasma, 14.2% in liver tissue, and 14.3% in kidney tissue. Tissue distribution studies showed that the highest platinum concentrations were found in the esophagus, followed by the kidney and liver. Compared with pre-implantation (day 0), there were no significant differences in most hematological indicators in Groups B and C (P > 0.05). Furthermore, histopathologic examination of the kidneys of dogs from Group C revealed no significant kidney damage. Unlike the intravenous CDDP group (Group A), no animals in the implantation groups showed any clinical signs of toxicity. CDDP-NP implants can be used to achieve a smooth pharmacokinetic curve and higher drug concentration, as well as a longer mean residence time at the implantation site, with reduced side effects compared with intravenous CDDP.

Carbon Nanomaterials Doped with Sulfur for ORR in Alkaline Media

Fuell cells are recognized as an attractive alternative for clean energy generation. However, their commercialization has been limited by the high cost of their components. Platinum supported on carbon (Pt/C) has been considered a conventional electrocatalyst due to their high electroactivity. However, recent researches works have shown that the free platinum electrocatalyst such as nanostructured carbons doped with heteroatoms (e. g. B, P, N and S) have similar electrocatalytic activities that Pt/C for oxygen reduction reaction (ORR) in alkaline media. This work present the behavior for ORR in alkaline media of nanomaterials based on carbon doped with sulfur. The materials were prepared using a modified chemical vapor deposition method. Toluene and thiophene was used as carbon and sulfur source, respectively, while ferrocene was used as growing agent. Nanocarbons morphology and textural properties are investigated by high resolution transmission and scanning microscopy, X Ray diffraction and Raman spectroscopy. Electrochemical analysis was evaluated using cyclic voltammetry (CV) and rotating disk electrode (RDE) in 0.1 M KOH media.

Superselective Intra-arterial Infusion Chemotherapy with Nedaplatin for Oral Cancer: A Pharmacological Study of the Dose Clearance.

Nedaplatin (cis-diammine-glycolate platinum) is a new anticancer agent developed in Japan. It is especially designed to reduce adverse side effects of CDDP such as renal toxicity and neurotoxicity. We used nedaplatin as a superselective intra-arterial infusion chemotherapy for oral cancers and carried out a pharmacological study of the dose clearance of nedaplatin based on renal function as well as evaluating its efficacy, including hematological side effects. Typical regimens of this chemotherapy consisted of 5-days straight of 24-h continuous intravenous infusion of 5-Fu with a single shot of nedaplatin via transfemoral artery on day 4. The dose of nedaplatin was calculated based on the 24-h creatine clearance. A total of 37 patients who had oral cancer and had received 68 courses (total) of chemotherapy were found to be eligible for this study. Total and free platinum concentrations in the plasma were measured at each of the time points, and the area under the curve (AUC, measured in units of µgh/ml) was calculated based on the platinum concentration with the following formula: CL (clearance of free platinum: l/h)=0.042×CCr (ml/min)+5.84. The response rate was 70.1% (in CR 51%, in PR 19%). Histological CR was seen in 28.6% of surgical specimens. Moderate hematological side effects were seen. However, severe adverse events were not observed, including those associated with cannulation of the femoral artery. The dose-clearance formula that was established by our study can most likely be utilized to accurately predict the optimal administered dose of nedaplatin for arterial infusion chemotherapy.