Psychotropic drugs and liver disease:A critical review of pharmacokinetics and liver toxicity

The liver is the organ by which the majority of sub-stances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolization of psychotropic drugs. This fact is particularly true in drugs with extensive first--pass metabolism, highly protein bound drugs and drugs depending on phase I hepatic metabolic reactions. Psychopharmacological agents are also associated with a risk of hepatotoxicity. The evidence is insufficient for definite conclusions regarding the prevalence and severity of psychiatric drug-induced liver injury. High-risk psychotropics are not advised when there is pre-existing liver disease, and after starting a psychotropic agent in a patient with hepatic impairment, frequent liver function/lesion monitoring is advised. The authors carefully review the pharmacokinetic disturbances induced by end-stage liver disease and the potential of psychopharmacological agents for liver toxicity.

3D bioprinting of in vitro porous hepatoma models:establishment,evaluation,and anticancer drug testing

Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study describes the use of threedimensional(3D)bioprinting technology to construct a 3D model with human hepatocarcinoma SMMC-7721 cells(3DP-7721)by combining gelatin methacrylate(GelMA)and poly(ethylene oxide)(PEO)as two immiscible aqueous phases to form a bioink and innovatively applying fluorescent carbon quantum dots for long-term tracking of cells.The GelMA(10%,mass fraction)and PEO(1.6%,mass fraction)hydrogel with 3:1 volume ratio offered distinct pore-forming characteristics,satisfactorymechanical properties,and biocompatibility for the creation of the 3DP-7721 model.Immunofluorescence analysis and quantitative real-time fluorescence polymerase chain reaction(PCR)were used to evaluate the biological properties of the model.Compared with the two-dimensional culture cell model(2D-7721)and the 3D mixed culture cell model(3DM-7721),3DP-7721 significantly improved the proliferation of cells and expression of tumor-related proteins and genes.Moreover,we evaluated the differences between the three culture models and the effectiveness of antitumor drugs in the three models and discovered that the efficacy of antitumor drugs varied because of significant differences in resistance proteins and genes between the three models.In addition,the comparison of tumor formation in the three models found that the cells cultured by the 3DP-7721 model had strong tumorigenicity in nude mice.Immunohistochemical evaluation of the levels of biochemical indicators related to the formation of solid tumors showed that the 3DP-7721 model group exhibited pathological characteristics of malignant tumors,the generated solid tumors were similar to actual tumors,and the deterioration was higher.This research therefore acts as a foundation for the application of 3DP-7721 models in drug development research.

Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review

The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

Body Composition as A Determinant of Pharmacokinetics and Toxicity of Anticancer Drugs

Chemotherapy-induced toxicity,resulting from inter-individual variability in pharmacokinetics is emerging as a highly active area of investigation.Body composition analysis,primarily concerning the amount of fat mass(FM)and lean body mass(LBM),has provided a proof-concept that the inter-individual variability in pharmacokinetics and toxicity profiles may be partially explained by the discrepancies of FM and LBM in patients.Recent research suggests a close relationship among body composition,pharmacokinetics and toxicity of anticancer drugs.Because LBM and FM,significantly influence the exposure to drugs,they are considered as the promising predictors of chemotherapy-induced toxicity and a potential basis for optimizing the dosing of oncology drugs and the outcomes.Our review summarizes the recent studies rendering the aforementioned correlations to highlight that a critical evaluation of body composition has initiated a new era for dose standardization.

Antitumor Effects and Acute Oral Toxicity Studies of a Plant Extract Mixture Containing <i>Rhus verniciflua</i>and Some Other Herbs

A novel antitumor agent was developed from six kinds of herbs containing Rhus verniciflua (Rv-PEM01). The components were traditionally established for each formula for traditional medicine. The formula was designed to affect antitumor effect as well as maintain host immune functions. First, we investigated the antiproliferative activities of Rv-PEM01 on human and canine tumor cell lines in vitro, and on antitumor effects using BALB/cAJcl-nu/nu mice in vivo. Acute oral toxicity of Rv-PEM01 was also investigated in vivo in ddY mice. Rv-PEM01 exhibited antiproliferative activities against PC-3 (IC50: 0.328 ± 0.081 mg/ml), A549 (IC50: 0.520 ± 0.070 mg/ml), D-17 (IC50: 0.124 ± 0.037 mg/ml) and MRC-5 (IC50: 0.505 ± 0.058 mg/ml) cells. Luteolin 7-β-D-glucopyranoside and apigenin 7-β-D-glucopyranoside were identified as the main active compounds in Rv-PEM01 by HPLC analysis. The single dose toxicity study of Rv-PEM01 did not result in any deaths or abnor-malities in daily behavior, body weight gain, or anatomical observations at necropsy. Thus, so we could not calculate the 50% lethal dose (LD50) in mice, but it would be higher than 5.0 g/kg. Treat- ment with Rv-PEM01 at a dose of 2.5 g/kg tended to show antitumor activities on mice bearing Colon26 tumors compared with the control group. It was concluded that the formula was a safe antitumor agent with no side effects on mouse physiological function as judged by survival and organ weight.

Amphotericin B release rate is the link between drug status in the liposomal bilayer and toxicity

Amphotericin B(AmB)is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections.Recent studies on the liposomal drug product have shed light on the AmB aggregation status in the bilayer,which heat treatment(curing)modifies.Although toxicity was found related to aggregation status-loose aggregates significantly more toxic than tight aggregates-the precise mechanism linking aggregation and toxicitywas notwell understood.This study directlymeasured drug release rate fromvarious AmB liposomal preparations made with modified curing protocols to evaluate correlations among drug aggregation state,drug release,and in vitro toxicity.UV–Vis spectroscopy of these products detected unique curing-induced changes in the UV spectral features:a∼25nm blue-shift of the main absorption peak(λ_(max))in aqueous buffer and a decrease in the OD_(346)/OD_(322) ratio upon thermal curing,reflecting tighter aggregation.In vitro release testing(IVRT)data showed,by applying and fitting first-order release kinetic models for one or two pools,that curing impacts two significant changes:a 3–5-fold drop in the overall drug release rate and a ten-fold decrease in the ratio between the loosely aggregated and the tightly aggregated,more thermodynamically stable drug pool.The kinetic data thus corroborated the trend independently deduced from the UV–Vis spectral data.The in vitro toxicity assay indicated a decreased toxicity with curing,as shown by the significantly increased concentration,causing half-maximal potassium release(TC50).The data suggest that the release of AmB requires dissociation of the tight complexes within the bilayer and that the reduced toxicity relates to this slower rate of dissociation.This study demonstrates the relationship between AmB aggregation status within the lipid bilayer and drug release(directly measured rate constants),providing a mechanistic link between aggregation status and in vitro toxicity in the liposomal formulations.

Thiopurine S-methyltransferase polymorphisms and thiopurine toxicity in treatment of inflammatory bowel disease

AIM: To evaluate the relationship between thiopu- rine S-methyltransferase (TPMT) polymorphisms and thiopurine-induced adverse drug reactions (ADRs) in inflammatory bowel disease (IBD). METHODS: Eligible articles that compared the frequency of TPMT polymorphisms among thiopurine-tolerant and-intolerant adult IBD patients were included. Statistical analysis was performed with Review Manager 5.0. Sub-analysis/sensitivity analysis was also performed. RESULTS: Nine studies that investigated a total of 1309 participants met our inclusion criteria. The inci- dence of TPMT gene mutation was increased 2.93-fold (95% CI: 1.68-5.09, P = 0.0001) and 5.93-fold (95% CI: 2.96-11.88, P < 0.00001), respectively, in IBD patients with thiopurine-induced overall ADRs and bone marrow toxicity (BMT), compared with controls. The OR for TPMT gene mutation in IBD patients withthiopurine-induced hepatotoxicity and pancreatitis was 1.51 (95% CI: 0.54-4.19, P = 0.43) and 1.02 (95% CI: 0.26-3.99, P = 0.98) vs controls, respectively. CONCLUSION: This meta-analysis suggests that the TPMT polymorphisms are associated with thiopurine-induced overall ADRs and BMT, but not with hepatotoxicity and pancreatitis.

Skin toxicity predicts efficacy to sorafenib in patients with advanced hepatocellular carcinoma

AIM:To study the relationship between adverse events(AEs),efficacy,and nursing intervention for sorafenibtherapy in patients with hepatocellular carcinoma(HCC).METHODS:We enrolled 37 consecutive patients withadvanced HCC who received sorafenib therapy.Relationships among baseline characteristics as well as AEoccurrence and tumor response,overall survival(OS),and treatment duration were analyzed.The nursingintervention program consisted of education regardingself-monitoring and AEs management,and telephoneRESULTS:A total of 37 patients were enrolled in the study,comprising 30 males(81%) with a median age of 71 years.The disease control rate at 3 mo was 41%,and the median OS and treatment duration were 259 and 108 d,respectively.Nursing intervention was given to 24 patients(65%).Every patient exhibited some kinds of AEs,but no patients experienced G4 AEs.Frequently observed AEs > G2 included anorexia(57%),skin toxicity(57%),and fatigue(54%).Factors significantly associated with longer OS in multivariate analysis demonstrated that age ≤ 70 years,presence of > G2 skin toxicity,and absence of > G2 hypoalbuminemia.The disease control rate in patients with > G2 skin toxicity was 13/20(65%),which was significantly higher compared with that in patients with no or G1 skin toxicity.Multivariate analysis revealed that nursing intervention and > G2 skin toxicity were independent significant predictors for longer treatment duration.CONCLUSION:Skin toxicity was associated with favorable outcomes with sorafenib therapy for advanced HCC.Nursing intervention contributed to better adher-ence,which may improve the efficacy of sorafenib.

Neurotoxicity of intrathecal injections of dexmedetomidine into the rat spinal dorsal horn

To investigate the neurotoxicity of intrathecal injections of dexmedetomidine,Sprague-Dawley rats were intrathecally injected with dexmedetomidine at doses of 0.75,1.50 and 3.00μg/kg into the spinal dorsal horn.We found that c-Fos expression in the rat spinal dorsal horn peaked at 7 hours following the 3.00μg/kg dexmedetomidine injection,while the levels of c-Fos expression following 0.75 and 1.50μg/kg dexmedetomidine were similar to those in the spinal dorsal horn of normal rats. At 48 hours following administration,the level of c-Fos expression was similar to normal levels.In addition,the intrathecal injections of dexmedetomidine increased paw withdrawal mechanical thresholds and prolonged thermal tail flick latencies.These results indicate that dexmedetomidine has pronounced antinociceptive effects.However,dexmedetomidine appears to have neurotoxic effects in the spinal cord because it increased c-Fos expression in the spinal dorsal horn within 7 hours following administration.

High-density lipoprotein as a potential carrier for delivery of a lipophilic antitumoral drug into hepatoma cells

AIM: To investigate the possibility of recombinant highdensity lipoprotein (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells. METHODS: Recombinant complex of HDL and aclacinomycin (rHDL-ACM) was prepared by cosonication of apoproteins from HDL (Apo HDL) and ACM as well as phosphatidylcholine. Characteristics of the rHDL-ACM were elucidated by electrophoretic mobility, including the size of particles, morphology and entrapment efficiency. Binding activity of rHDL-ACM to human hepatoma cells was determined by competition assay in the presence of excess native HDL. The cytotoxicity of rHDL-ACM was assessed by MTT method. RESULTS: The density range of rHDL-ACM was 1.063-1.210 g/mL, and the same as that of native HDL. The purity of all rHDL-ACM preparations was more than 92%. Encapsulated efficiencies of rHDL-ACM were more than 90%. rHDL-ACM particles were typical sphere model of lipoproteins and heterogeneous in particle size. The average diameter was 31.26±5.62 nm by measure of 110 rHDL-ACM particles in the range of diameter of lipoproteins. rHDL-ACM could bind on SMMC-7721 cells, and such binding could be competed against in the presence of excess native HDL. rHDL-ACM had same binding capacity as native HDL. The cellular uptake of rHDL-ACM by SMMC-7721 hepatoma cells was significantly higher than that of free ACM at the concentration range of 0.5-10 μg/mL (P<0.01). Cytotoxicity of rHDL-ACM to SMMC-7721 cells was significantly higher than that of free ACM at concentration range of less than 5 ug/mL (P<0.01) and IC50 of rHDL-ACM was lower than IC50 of free ACM (1.68 nmol/L vs3 nmol/L). Compared to L02 hepatocytes, a normal liver cell line, the cellular uptake of rHDL-ACM by SMMC-7721 cells was significantly higher (P<0.01) and in a dose-dependent manner at the concentration range of 0.5-10 μg/mL.Cytotoxicity of the rHDL-ACM to SMMC- 7721 cells was significantly higher than that to L02 cells at concentration range of 1-7.5μg/mL (P<0.01). IC50 for SMMC-7721 cells (1.68 nmol/L) was lower than that for L02 cells (5.68 nmol/L), showing a preferential cytotoxicity of rHDL-ACM for SMMC-7721 cells. CONCLUSION: rHDL-ACM complex keeps the basic physical and biological binding properties of native HDL and shows a preferential cytotoxicity for SMMC-7721 hepatoma to normal L02 hepatocytes, HDL is a potential carrier for delivering lipophilic antitumoral drug to hepatoma cells.

Thiopurine-methyltransferase variants in inflammatory bowel disease:Prevalence and toxicity in Brazilian patients

AIM: To analyze the prevalence of thiopurine-methyltransferase (TPMT) genotypes and their association with drug toxicity in inflammatory bowel disease (IBD) patients from southeastern Brazil.

Evaluation of antihepatotoxic potential of Solanum xanthocarpum fruit extract against antitubercular drugs induced hepatopathy in experimental rodents

Objective:To assess the hepatoprotective effect of Solanum xanthocarpum(S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.Methods:Ethanolic(50%) fruit extract ofS. xanthocarpum(100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid(I) 7.5 mg/kg, rifampicin(R) 10 mg/kg and pyrazinamide(P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatise(ALP), total bilirubin(TBL), albumin(ALB), total protein(TP), lactate dehydroginase(LDH), and serum cholesterol(CHL). Meanwhile,in vivoantioxidant activities as lipid peroxidation(LPO), reduced glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination.Results:The results demonstrated that treatment withS.xanthocarpumsignificantly(P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore,S. xanthocarpumsignificantly(up toP<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpumattenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration.Conclusions:The results of this study strongly indicate the protective effect of S. xanthocarpumagainst liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.

A review: Systematic research approach on toxicity model of liver and kidney in laboratory animals

Therapeutic experiments are commonly performed on laboratory animals to inves-tigate the possible mechanism(s)of action of toxic agents as well as drugs or sub-stances under consideration.The use of toxins in laboratory animal models,including rats,is intended to cause toxicity.This study aimed to investigate different models of hepatotoxicity and nephrotoxicity in laboratory animals to help researchers advance their research goals.The current narrative review used databases such as Medline,Web of Science,Scopus,and Embase and appropriate keywords until June 2021.Nephrotoxicity and hepatotoxicity models derived from some toxic agents such as cisplatin,acetaminophen,doxorubicin,some anticancer drugs,and other materials through various signaling pathways are investigated.To understand the models of renal or hepatotoxicity in laboratory animals,we have provided a list of toxic agents and their toxicity procedures in this review.

Comparative study on pharmacokinetics and toxicity of intravitreal and sub-Tenon injection of triamcinolone acetonide in ocular tissues

AIM:To compare the differences in kinetics,distribution,and toxicity of triamcinolone acetonide(TA)between the injection methods,sub-Tenon and intravitreal injections in rabbit ocular tissues.METHODS:TA was injected into the vitreous or the sub-Tenon in rabbits.For pharmacokinetic study,rabbits were sacrificed periodically and then TA in blood and ocular tissues(retina/choroids,vitreous,and aqueous humor)were measured over 91 d.For toxicological study,clinical signs,slit-lamp microscopic examination,ophthalmological test were performed.The eyeballs and surrounding tissues were collected and fixed with glutaraldehyde-formalin solution,and then paraffin embedded for histological investigation.RESULTS:Higher levels of TA were distributed in the intraocular tissues when injected into the vitreous compared to the sub-Tenon.Conversely,TA level was remarkably lower in the rabbits which received intravitreal TA injections than those treated with sub-Tenon injection throughout the study period in plasma.Optical discharge probably caused by systemic circulation of TA was observed by receiving sub-Tenon TA injection.Meanwhile,technicassociated toxicological ocular symptoms and findings were more frequently observed in intravitreal injection than in sub-Tenon injection.CONCLUSION:There are significant differences in kinetics and distribution of TA in vitreous body,aqueous humor and plasma,between the two injection methods.Although further study is needed to explain the species difference between human and rabbit,it is assumed that the difference in the frequency of intraocular pressure elevation and cataract formation by TA between the two injection methods are directly related to the TA concentrations in aqueous humor and vitreous body in each injection methods.Systemic toxicity and technic-associated toxicity are also closely related to kinetics of TA in plasma and each injection method itself,respectively.

Prediction of nephrotoxicity induced by cisplatin combination chemotherapy in gastric cancer patients

AIM:To evaluate the treatment options for nephrotoxicity due to cisplatin combination chemotherapy.METHODS:We retrospectively reviewed patients who had received cisplatin combination chemotherapy for gastric cancer between January 2002 and December 2008.We investigated patients who had shown acute renal failure(ARF),and examined their clinical characteristics,laboratory data,use of preventive measures,treatment cycles,the amount of cisplatin administered,recovery period,subsequent treatments,and renal status between the recovered and unrecovered groups.RESULTS:Forty-one of the 552 patients had serum creatinine(SCR)levels greater than 1.5 mg/dL.We found that pre-ARF SCR,ARF SCR,and ARF glomerular filtration rates were significantly associated with renal status postARF between the two groups(P=0.008,0.026,0.026,respectively).On the receiver operating characteristic curve of these values,a 1.75 mg/dL ARF SCR value had 87.5%sensitivity and 84.8%specificity(P=0.011).CONCLUSION:Cessation or reduction of chemotherapy should be considered for patients who have an elevation of SCR levels during cisplatin combination chemotherapy.

Carbon nanotubes:A review on risks assessment,mechanism of toxicity and future directives to prevent health implication

Carbon nanotubes(CNTs)have tremendous applications in almost every walk of life;however,their harmful impacts on humans and the environment are not well addressed.CNTs have been used in various applications ranging from medical science to different engineering branches,to ease human life.Generally,the toxicological profile of CNTs under laboratory conditions cannot be assessed primarily in medical science due to the inconsistent availability of cytotoxic study data.CNT toxicity has been affected by many physicochemical properties(e.g.,size,type of functionalization),concentration,the extent of exposure,mode of exposure,and even the solvents/medium used to dissolve/disperse CNTs for their application.These inconsistencies arise due to the variation in synthesis methods as well as the mode of their human exposure.Besides their unlimited use in various fields,most of CNT toxicity aspects and mechanisms remain uncertain.Additionally,in-depth knowledge of CNTs toxicity is scarce,and the available literature shows dissimilarities in experimental data and exposure studies.To understand the toxicological issues,it is the need of the hour to provide insight into the published data,post-exposure studies,and various factors that may damage the cells due to CNTs toxicity.This review article analyses the hazardous potential through toxicological implications and summarizes the detailed mechanism(s)of CNTs studied on the different model organisms,including human cell lines.In this review article,we hypothesized that thorough knowledge of various aspects,as mentioned above,helps us design and develop possible strategies to reduce the toxicity of nanomaterial to make them safer and secure for humanity’s betterment.

Evaluation of Biotinylated PAMAM Dendrimer Toxicity in Models of the Blood Brain Barrier: A Biophysical and Cellular Approach

The interaction of biotinylated G4 poly(amidoamine) (PAMAM) dendrimer conjugates and G4 PAMAM dendrimers with in vitro models of the blood brain barrier (BBB) was evaluated using Langmuir Blodgett monolayer techniques, atomic force microscopy (AFM) and lactate dehydrogenase measures of cell membrane toxicity. Results indicate that both G4 and G4 biotinylated PAMAM dendrimers disrupt the composition of the liquid condensed (LC) and liquid expanded (LE) phases of the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid monolayer. The disruption is concentration dependent and more marked for G4 biotinylated PAMAMs. Lactate dehydrogenase (LDH) assays using endothelial cell culture models of the BBB indicate that biotinylation results in higher levels of toxicity than non-biotinylation. This approach provides valuable information to assess nanoparticle toxicity for drug delivery to the brain.

Recent advances in the development of in vitro liver models for hepatotoxicity testing

Liver injury is a common cause of drug approval withdrawal during drug development,pre-clinical research,and clinical treatment.If not properly treated,patients with severe liver injury can suffer from acute liver failure or even death.Thus,utilization of the convenient in vitro hepatotoxicity assessment model for early detection of drug-induced hepatotoxicity is vital for drug development and safe personalized medication.Biomaterials(e.g.,hydrogels,nanofibers,decellularized liver matrix)and bioengineering technologies(e.g.,microarrays,micropatterns,3D printing,and microfluidics)have been applied for in vitro hepatotoxicity assessment models.This review summarizes the structure and functions of the liver as well as the components of in vitro hepatotoxicity assessment models.In addition,it highlights the latest advances in developing hepatotoxicity models with the ultimate goal of further clinical translation.

Recent advances regarding the role of ABC subfamily C member 10(ABCC10) in the efflux of antitumor drugs

ABCC10,also known as multidrug-resistant protein 7(MRP7),is the tenth member of the C subfamily of the ATP-binding cassette(ABC) superfamily.ABCC10 mediates multidrug resistance(MDR) in cancer cells by preventing the intracellular accumulation of certain antitumor drugs.The ABCC10 transporter is a 171-kDa protein that is localized on the basolateral cell membrane.ABCC10 is a broad-specificity transporter of xenobiotics,including antitumor drugs,such as taxanes,epothilone B,vinca alkaloids,and cytarabine,as well as modulators of the estrogen pathway,such as tamoxifen.In recent years,ABCC10 inhibitors,including cepharanthine,lapatinib,erlotinib,nilotinib,imatinib,sildenafil,and vardenafil,have been reported to overcome ABCC10-mediated MDR.This review discusses some recent and clinically relevant aspects of the ABCC10 drug efflux transporter from the perspective of current chemotherapy,particularly its inhibition by tyrosine kinase inhibitors and phosphodiesterase type 5 inhibitors.

Development of NAMI-A-loaded PLGA-mPEG Nanoparticles:Physicochemical Characterization, in vitro Drug Release and in vivo Antitumor Efficacy

NAMI-A[imidazolium trans-tetrachloro(dimethylsulfoxide)imidazoleruthenium(Ⅲ)] shows extraordinary activities against metastatic tumors. However, the hydrolysis of NAMI-A to produce dimethyl sulfoxide(DMSO) could reduce anti-metastatic activity. To enhance the circulation time and the anti-metastatic effect of NAMI-A, NAMI-A-loaded nanoparticles were prepared by the double emulsion method and characterized by scanning electron microscopy for surface morphology, laser light scattering for size and zeta potential for surface charges. Controlled release of NAMI-A was observed in a sustained manner. Compared with free NAMI-A, NAMI-A-loaded nanoparticles exhibited superior antitumor effect by delaying tumor growth in T739 mice. PLGA-mPEG nanoparticles are promising for further studies as drug delivery carriers.