Cuiyun Li

China Pharmaceutical University, Nan-ching-hsü, Jiangxi Sheng, China

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Publications (13)26.13 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives The clinical application of doxorubicin (DOX) is limited by severe systemic side effects. The aim of this study was to develop a strategy that combined the liposomal DOX (LipDOX) and intratumoral injection to reduce the toxicity and enhance the antitumor efficiency.Methods The pharmacokinetics, tissue distribution and pharmacodynamics of LipDOX compared with free DOX were investigated by intratumoral injection in murine H22 hepatoma-bearing mice at a dose of 20 mg/kg body weight. A sensitive HPLC-tandem mass spectrometry method was used to determine the DOX levels in plasma and tissues. The tumour volume and body weight of mice were measured every 3 days.Key findingsLipDOX administration resulted in 1.3-fold longer mean residence time (MRT) and 2.4-fold higher area under concentration (AUC)-time curve compared with free DOX administration in tumour. Free DOX caused higher peak plasma concentration (Cmax) than LipDOX in plasma and major organs, which may result in significant mortality for acute cardiac toxicity. After successive 21 days treatment, the final volume of tumour treated by normal saline, free DOX and LipDOX was 5.0-, 1.3-fold higher and 1.6-fold lower than the initial tumour volume, respectively.Conclusions Our results indicated that the intratumoral injection of LipDOX is a promising approach with higher therapeutic efficacy and lower systemic toxicity than free DOX.
    Journal of Pharmacy and Pharmacology. 05/2014;
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    ABSTRACT: The compound series of traditional anticholinergics [atropine (Atr), anisodamine (Ani), anisodine (AT3), and scopolamine (Sco)], naturally occurring belladonna alkaloid, have been approved for numerous therapeutic uses since 1970s. Tiotropium, a novel M receptor antagonist for the treatment of chronic obstructive pulmonary disease, was structurally modified based on atropine-like drugs. Clinical phenomena suggested that the changes of substituent group were related to the pharmacokinetic and pharmacodynamic characteristics of the agents. In an attempt to compare the pharmacokinetics of the series of anticholinergics and investigate the subsets motivating selective anticholinergic potencies, a sensitive LC-MS/MS method was established to analyze the differences of pharmacokinetic parameters. In this paper, we determined the pharmacokinetics of atropine, anisodamine, anisodine, scopolamine, and tiotropium after i.v. and i.g. single dose administration. After i.v. administration, the maximum drug plasma concentrations (C max) of Atr, Ani, AT3, and Sco were 274.25 ± 53.66, 267.50 ± 33.16, 340.50 ± 44.52, and 483.75 ± 78.13 ng/mL. Tiotropium had a slightly higher area under the curve with a significant increase of C max value. Because of their partial solubility, Atr, Ani, AT3, and Sco had different bioavailability in rats of 21.62, 10.78, 80.45 and 2.52 %, respectively. Following i.g. administration of tiotropium, the C max value below 20 ng/mL revealed the very low oral absorption. The urinary excretion rates of Atr, Ani, AT3, Sco and tiotropium were 11.33, 54.86, 32.67, 8.69 and 73.91 %. This work provided relatively comprehensive preclinical data on the series of anticholinergics, which may be used to explain the clinical adverse effects and applications.
    European Journal of Drug Metabolism and Pharmacokinetics 04/2014; · 1.31 Impact Factor
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    ABSTRACT: Docetaxel (DTX) is a widely used anticancer drug for various solid tumors. However, its poor solubility in water and lack of specification are two limitations for clinical use. The aim of the study was to develop a thermosensitive chitosan/β-glycerophosphate (C/GP) hydrogel loaded with DTX for intratumoral delivery. The in vitro release profiles, in vivo antitumor efficacy, pharmacokinetics, and biodistribution of DTX-loaded C/GP hydrogel (DTX-C/GP) were evaluated. The results of in vitro release study demonstrated that DTX-C/GP had the property of controlled delivery for a reasonable time span of 3 weeks and the release period was substantially affected by initial DTX strength. The antitumor efficacy of DTX-C/GP was observed at 20 mg/kg in H22 tumor-bearing mice. It was found that the tumor volume was definitely minimized by intratumoral injection of DTX-C/GP. Compared with saline group, the tumor inhibition rate of blank gel, intravenous DTX solution, intratumoral DTX solution, and DTX-C/GP was 2.3%, 29.8%, 41.9%, and 58.1%, respectively. Further, the in vivo pharmacokinetic characteristics of DTX-C/GP correlated well with the in vitro release. DTX-C/GP significantly prolonged the DTX retention and maintained a high DTX concentration in tumor. The amount of DTX distributed to the normal tissues was minimized so that the toxicity was effectively reduced. In conclusion, DTX-C/GP demonstrated controlled release and significant efficacy and exhibited potential for further clinical development.
    AAPS PharmSciTech 01/2014; · 1.58 Impact Factor
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    ABSTRACT: Abstract 1. Triacontanol was confirmed to have a potential anti-cancer effect, the aim was to assess whether the co-administration of triacontanol alters the exposure of docetaxel via inducing hepatic CYP3A1/2 activity. The concentration of docetaxel in rats pretreated with triacontanol for seven successive days was determined, and the expression levels of CYP3A protein and mRNA were analyzed by the western blot and real time polymerase chain reaction (RT-PCR) technique, respectively. 2. The concentrations of docetaxel in rats pretreated with triacontanol were decreased, with 61.5%, 61.9% decrease in AUC0-24h and 65.7%, 54.9% reduction in Cmax (120 and 180 mg kg(-1), respectively) compared with the control. Hepatic clearance of docetaxel was enhanced in vitro and in vivo at dosage of 120 and 180 mg kg(-1), and CYP3A activity was up-regulated by measuring the formation rate of 1-hydroxymidazolam. Triacontanol preferentially induced protein expression level of CYP3A2 in a dose-dependent manner and of CYP 3A1 at dosage of 120 and 180 mg kg(-1). The mRNA expression of CYP3A1 was moderately different with the western blot results, but the trends appeared similar. CYP3A2 mRNA level was not markedly affected by triacontanol. 3. The significant triacontanol-docetaxel interaction was largely due to the induction of CYP3A1/2, which brought useful information in the clinical therapy when the combination is administered in human.
    Xenobiotica 12/2013; · 1.98 Impact Factor
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    ABSTRACT: Abstract 1. MXN-004 is a water-soluble PEGylated 7-ethyl-10-hydroxy-camptothecin (SN38). The aim of this study was to evaluate the in vitro cytotoxicity of MXN-004 and investigate pharmacokinetics and tissue distribution of MXN-004 and its active metabolite SN38 in rats. 2. In vitro cytotoxicity of MXN-004 was tested in A549, HepG2 and Caco-2 cancer cell lines by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and compared with irinotecan. The pharmacokinetics and tissue distribution of MXN-004, irinotecan and their identical active metabolite SN38 were investigated after intravenous administration of MXN-004 and irinotecan at a same dose level of 16 μmol/kg in rats. 3. In vitro cytotoxicity study showed that MXN-004 was more potent in comparison with irinotecan. In rats, MXN-004 exhibited a longer half-life (sixfold) and much greater Vss as compared with irinotecan. The AUC0-∞, T1/2 and Cmax of SN38 after intravenous administration of MXN-004 were higher than those of irinotecan (3.5-, 1.92- and 10.6-fold, respectively). In addition, the concentrations of SN38 released from MXN-004 were significantly higher in all tissues than those from irinotecan, especially in the lung. 4. These results suggested that MXN-004 might be a more potential water-soluble antitumor agent with prolonged half-life of SN38 compared to irinotecan.
    Xenobiotica 12/2013; · 1.98 Impact Factor
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    ABSTRACT: Nanoparticles are being increasingly recognized for their potential utility in biological applications including nanomedicine. The aim of this study is to investigate a new strategy to combine the ZnO nanoparticles with graphene for targeting photodynamic therapy (PDT) under visible light irradiation. Folic acid (FA), a targeting agent toward tumor cells, was conjugated onto graphene oxide (GO) via imide linkage. Using a simple and effective chemical precipitation method, a GO–FA–ZnO nanohybrid was then prepared. The combination of ZnO with GO–FA induced a remarkable improvement in tumor targeting, which has been demonstrated by the cellular uptake assay. Due to the high electrical conductivity of graphene, the interaction between graphene and ZnO, and the inhibition of aggregation, the hybrid of GO–FA and ZnO significantly enhances the photodynamic activity. It was noted that the photodynamic activity of the non-cytotoxic GO–FA–ZnO is mediated by reactive oxygen species (ROS) generation under visible light irradiation. Following the ROS generation, GO–FA–ZnO caused a significant decrease in cell viability, mitochondrial membrane potential, superoxide dismutase activity, catalase and glutathione peroxidase, as well as an increase in malonodialdehyde production. Moreover, GO–FA–ZnO induced apoptotic death by elevating the caspase-3 activity. The study presents a novel tumor targeting photosensitizer and a promising strategy in PDT for cancer treatment.
    J. Mater. Chem. B. 09/2013; 1(38).
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    ABSTRACT: Iron is a challenging element due to its high background in various matrixes including blood, tissues even in the air and it is urgent to develop a method for the accurate determination of iron in bio-samples. After optimization of mass spectrometric conditions using collision cell technology and compensating for interference using a mathematical correction equation, an inductively coupled plasma mass spectrometry (ICP-MS) method for the quantitative determination of (58)Fe originating from hemin extrinsically labeled avoiding endogenous interference was developed. After a single step of dilution, analysis of each sample was completed within 1.5min. The assay was linear in the concentration range from 0.005 to 1.0μg/ml. The precisions and accuracies determined within three consecutive days were in acceptable limits and there was no significant matrix effect. The optimized method was successfully applied to a pharmacokinetic study of (58)Fe originating from hemin extrinsically labeled and iron absorption measured in rats was 1.07%. Those indicated that extrinsically label techniques in combination with ICP-MS will become a new tool for the analysis of iron preparations and other endogenous substances.
    Journal of pharmaceutical and biomedical analysis 09/2013; 88C:331-336. · 2.45 Impact Factor
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    ABSTRACT: Poly(p-phenylene benzobisoxazole) (PBO) fibers are some of the strongest organic polymer fibers, however, even stronger fibers can be made using carbon nanotubes (CNTs). In the present study, the copolymerization of functionalized CNTs with PBO was successfully carried out by one-pot in situ polycondensation in polyphosphoric acid. Pristine CNTs were first oxidized to CNT–COOH and then modified by 4,6-diaminoresorcinol (DAR) or PBO trimer (DAR–TA–DAR) to improve the reactivity, solubility, dispersivity, and interfacial adhesion of CNTs in polymer matrix. Functionalized CNTs were further covalently incorporated with PBO through in situ polymerization. The chemical structure and morphology of functionalized CNTs and CNT–PBO copolymers were well characterized for confirming the formation of covalent bond between CNTs and PBO. Moreover, continuous CNT–PBO copolymer fibers have been fabricated using a dry-jet wet-spinning technique. The structure and morphology of CNT–PBO copolymer fibers have been characterized and their mechanical and thermal properties have been investigated. The tensile modulus, tensile strength, and thermal stability of CNT–PBO copolymer fibers have been improved. The improvement in PBO molecular chain packing order, the good dispersion and high alignment of CNTs in the PBO matrix, and the covalent bonding at the CNT–PBO interface have been suggested as the main reasons for the performance improvement of PBO.
    Journal of Materials Chemistry 08/2012; 22(37):19863-19871. · 5.97 Impact Factor
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    ABSTRACT: The influence of the glutathione C₆₀ derivative on the cytotoxicity of a highly reactive free radical NO (nitric oxide) has been investigated. Consistent with its cytoprotective abilities, the derivative scavenges ROS (reactive oxygen species) and RNS (reactive nitrogen species) both in vitro and under cell-free conditions. Moreover, the glutathione C₆₀ derivative protected PC12 cells from the cytotoxic effect of the NO-releasing compound, SNP (sodium nitroprusside). Addition of glutathione C₆₀ derivative alone did not induce apoptosis and necrosis. The results suggest that the glutathione C₆₀ derivative has the potential to prevent NO-mediated cell death without evident toxicity.
    Cell Biology International 03/2012; 36(7):677-81. · 1.64 Impact Factor
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    ABSTRACT: Graphene oxide/TiO2 hybrid (GOT) was prepared by using Ti(OC4H9)4 and graphene oxide (GO) as reactants. Superior adsorption and photocatalysis performance under visible radiation were achieved in the presence of the GOT rather than in unmodified TiO2. GO that no toxicity in vitro acted as electron sink in GOT efficiently enhance the photodynamic activities. Consistent with photocatalytic performance of TiO2, GOT generated reactive oxygen species after visible light irradiation both in cell free condition and in vitro. No dark cytotoxicity was observed using 0–100μg/mL GOT during long incubation time. In parallel, following exposure of cells to GOT and irradiation, a marked decrease in mitochondrial membrane potential, cell viability, activities of superoxide dismutase, catalase and glutathione peroxidase, as well as increased malondialdehyde production were observed. Moreover, GOT caused significant elevation in caspase-3 activity, and induced apoptotic death. The results indicated that GOT had excellent photodynamic anticancer activity without dark cytotoxicity.
    Carbon. 03/2012;
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    ABSTRACT: Dicycloplatin, as a new antitumor supramolecule, was considered to have higher solubility and higher stability compared with carboplatin. The aim of the present study was to evaluate the pharmacokinetic characteristics of platinum originating from dicycloplatin. A rapid, sensitive, and specific method with inductively coupled plasma mass spectrometry (ICP-MS) has been developed for the determination of platinum in bio-samples. The study was performed in male rats and dogs at a single dose of 10 and 5 mg kg(-1) separately by intravenous injection. Pharmacokinetic parameters were calculated by non-compartmental method, and the dose of platinum was used in the calculation of these parameters. Results showed that plasma concentrations of platinum began to decrease rapidly initially but decline slowly with a long terminal phase. The mean half-life was 27.39 and 100.98 and clearance was 0.77 and 0.08 L/h/kg for rats and dogs separately. Tissue distribution showed that platinum originating from dicycloplatin had a certain distribution in testis and prostate. Plasma protein binding proportion of platinum was increased with time. In conclusion, this research investigated the pharmacokinetic characteristics including plasma kinetics, tissue distribution, and plasma protein binding of platinum originating from dicycloplatin in rats and dogs in detail for the first time by ICP-MS.
    Biological trace element research 02/2012; 148(2):203-8. · 1.92 Impact Factor
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    ABSTRACT: (Z)-2-amino-1,5-dihydro-1-methyl-5-[4-(mesyl)benzylidene]-4H-imidazol-4-one mesilate (ZLJ-601) is an imidazolone COX/5-LOX inhibitor, which has excellent anti-inflammatory activity with an improved gastrointestinal safety profile. The purpose of this study was to evaluate the in vivo absorption, distribution, metabolism, and excretion of ZLJ-601 in Sprague-Dawley rats. After intravenous or intragastric administration to rats, the concentration of ZLJ-601 in plasma, bile, urine, feces and various types of tissues was detected by LC-MS. We also conducted the identification of metabolites using tandem mass spectrometry. After the intravenous administration, the t1/2 ranged from 38.71 to 42.62 min and the AUC increased in a dose-proportional manner. After oral dosing, the plasma level of ZLJ-601 peaked at 28.33 min, having a Cmax value of 0.26 mg/l, and the bioavailability was only 4.92%. The highest tissue concentration of ZLJ-601 was observed in lung and kidney, but it was not found in brain. The majority of unchanged ZLJ-601 was excreted in urine (∼35.87%) within 36 h. Two main metabolites are the hydroxylation product and the glucuronide conjugate of the hydroxylation product.Copyright © 2012 S. Karger AG, Basel
    Pharmacology 01/2012; 89:192-200. · 1.60 Impact Factor
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    ABSTRACT: Carbon nanotube (CNT)-organic polymer hybrids have important potential applications in the immobilization of therapeutic biomolecules. Recently developed CNT-organic polymer composites require the use of organic solvents for their preparation and have limited polymer functionalization. To address these limitations, multi-walled CNT (MWCNT)-chitosan nanoparticle (CS NP) hybrids have been synthesized in situ by an ionotropic gelation process, which is extremely mild and involves the mixture of two aqueous solutions at room temperature. The MWCNT-CS NP hybrids were characterized by atomic force microscopy and thermogravimetric analysis. Under optimal conditions the CS NP can be tethered to the MWCNT surface in high density and with relatively uniform coverage. The MWCNT-CS NP hybrids show good dispersibility and stability in aqueous solutions. In order to evaluate the potential utilization of the hybrids as protein carries the cytotoxicity to HeLa cells and protein immobilization (of bovine serum albumin (BSA), used here as a model) capacity of the hybrids were investigated in detail. The results demonstrate that the MWCNT-CS NP hybrids are biocompatible at concentrations up to 100 μg mL(-1) for 24 h incubation. The MWCNT-CS NP hybrids improve the BSA immobilization efficiency 0.8 times and simultaneously decrease the cellular toxicity by about 50% compared with carboxylated MWCNT.
    Acta biomaterialia 05/2011; 7(8):3070-7. · 5.68 Impact Factor

Publication Stats

13 Citations
26.13 Total Impact Points

Institutions

  • 2012–2013
    • China Pharmaceutical University
      • Center of Drug Metabolism and Pharmacokinetics
      Nan-ching-hsü, Jiangxi Sheng, China
    • Harbin Institute of Technology
      • School of Chemical Engineering and Technology
      Charbin, Heilongjiang Sheng, China
  • 2011
    • Hunan University
      • College of Chemistry and Chemical Engineering
      Changsha, Hunan, China