RESUMEN

In the present work, for the first time, fully green maltodextrin nanosponges (MDNSs) as extraction phases for the preparation of magnetic sorbents were introduced. All of the raw materials and synthetic methodologies used to prepare MDNSs follow the principles of green chemistry. Fluoroquinolones (FQs) (ofloxacin, ciprofloxacin, enrofloxacin, and moxifloxacin) were used as model analytes to assess the extraction performance of MDNSs in magnetic solid-phase extraction (MSPE) procedure. Under the optimized conditions, the developed MSPE was coupled with HPLC-UV to sensitively quantify trace levels of four FQs in tap water, wastewater, and river water samples. The proposed MSPE-HPLC-UV method provided wide linearity in the range of 0.25-500.0 ng mL-1 with determination coefficients ≥0.9997. Low limits of detection (LODs ≤0.06 ng mL-1) and quantification (LOQs ≤0.20 ng mL-1) were achieved. Furthermore, the developed green extraction phases compared with all other maltodextrin-based extraction phases were promising.

Asunto(s)

Fluoroquinolonas , Aguas Residuales , Cromatografía Líquida de Alta Presión/métodos , Ciprofloxacina , Enrofloxacina , Fenómenos Magnéticos , Moxifloxacino , Ofloxacino , Polisacáridos , Extracción en Fase Sólida/métodos , Agua

RESUMEN

Development of versatile medical dressing with good immediate and long-lasting antibacterial, hygroscopic and moisturizing abilities is of great significance for management of chronic wounds. Cotton gauze (CG) can protect wounds and promote scabbing, but can cause wound dehydration and loss of biologically active substances, thereby greatly delays wound healing. Herein, a bi-functional CG dressing (CPCG) was developed by chemically grafting polyhexamethylene guanidine (PHMG) and physically adsorbing chitosan (CS) onto the CG surface. Due to the powerful microbicidal activity of PHMG, CPCG exhibited excellent immediate and long-lasting antibacterial activity against gram-positive and gram-negative bacteria. Moreover, the abundant hydroxyl and amino groups in CS endowed CPCG with good biocompatibility, moisture absorption, moisturizing and cell scratch healing performances. Importantly, CPCG can be easily fabricated into a bandage to conveniently manage infected full-skin wounds. Together, this study suggests that CPCG is a versatile wound dressing, having enormous application potential for management chronic wounds.

Asunto(s)

Antibacterianos , Vendajes , Quitosano , Fibra de Algodón , Guanidinas , Animales , Movimiento Celular , Células Cultivadas , Eritrocitos , Escherichia coli/crecimiento & desarrollo , Femenino , Hemólisis , Humanos , Ratones Endogámicos BALB C , Staphylococcus aureus/crecimiento & desarrollo , Cicatrización de Heridas , Infección de Heridas/prevención & control

RESUMEN

Hydrogels, being highly biocompatible and adaptable with biological tissues, have shown great usability in biomedical applications. In this research, a novel hydrogel film developed from carboxymethyl chitosan (CMCS) loaded with waterborne polyurethane-gelatin hydrolysate was synthesized via aqueous emulsion copolymerization. The synthesized hydrogel film was characterized using mechanical strength tests, FTIR, XPS, SEM, AFM, and various other analysis technologies. The results demonstrated that the hydrogel film exhibited good thermal stability, swelling behavior, as well as controllable biodegradability. Specifically, when the CMCS content was loaded at 6 %, the maximum tensile strength and elongation at the break of the hydrogel film were reached 31.69 MPa and 447.187, respectively. The disk diffusion tests indicated that the hydrogel film presented significant antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). These results indicate that hydrogel films with high mechanical strength and high antibacterial activity could be used for wound dressing applications.

Asunto(s)

Vendajes , Materiales Biocompatibles/química , Quitosano/análogos & derivados , Escherichia coli/efectos de los fármacos , Metilgalactósidos/química , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Biomasa , Líquidos Corporales/efectos de los fármacos , Quitosano/química , Emulsiones , Gelatina/química , Humanos , Hidrogeles/química , Poliuretanos/química , Espectroscopía Infrarroja por Transformada de Fourier , Estrés Mecánico , Resistencia a la Tracción , Termogravimetría , Agua/química

RESUMEN

The novel molecularly imprinted microspheres for four phenylarsonic compounds have been firstly prepared with the reversible addition-fragmentation chain transfer polymerization in a suspension system. The resulting polymeric microspheres were characterized by infrared spectrum, scanning electron microscope and differential scanning calorimetry. With serial adsorption experiments, the polymeric microspheres showed highly specific molecular recognition, fast mass transfer rate and robust adsorption of the substrates. Then, the imprinted polymer was used as the solid-phase extraction adsorbent to extract the phenylarsonic compounds from the feeds, edible chicken and pork. The cartridge was washed with 2 mL ethyl acetate and eluted with 3 mL of methanol- acetic acid (90:10, v/v). The recoveries of the molecularly imprinted solid-phase extraction (MISPE) column ranged from 83.4% to 95.1%. This work provided a versatile approach for the specific extraction of the organoarsenic compounds from complicated matrices and exhibited a bright future for the application of MISPE column.

Asunto(s)

Alimentación Animal/análisis , Arsenicales/análisis , Carne/análisis , Impresión Molecular , Polímeros/química , Extracción en Fase Sólida/métodos , Adsorción , Animales , Ácido Arsanílico/análogos & derivados , Ácido Arsanílico/análisis , Ácido Arsanílico/aislamiento & purificación , Arsenicales/aislamiento & purificación , Pollos , Cromatografía Líquida de Alta Presión , Músculos/química , Roxarsona/análisis , Roxarsona/aislamiento & purificación , Porcinos

RESUMEN

Three kinds of novel environmentally benign and high-efficiency crude oil demulsifiers were prepared using methoxy polyethylene glycol (MPEG) to modify alkylated carboxymethyl chitosan (ACMC). Structures of the demulsifiers were confirmed using FT-IR and 1H NMR, and the relationship between surface tension and concentration was tested. Demulsification performance was investigated using the bottle test method with oil-in-water (O/W) emulsions that were prepared in lab conditions. The demulsification efficiency was as high as 79.1 %-84.9 %, and the possible mechanism of the demulsification process is discussed. Results show that MPEG-grafted ACMC (MPEG-ACMC) has a promising application as a demulsifier for dealing with emulsified O/W crude oil.

Asunto(s)

Quitosano/análogos & derivados , Emulsiones/química , Petróleo , Quitosano/química , Polietilenglicoles/química

RESUMEN

It is still a challenge to solve the matrix interferences in veterinary drug residue analysis. In this study, we reported a thin layer chromatography (TLC)-high-performance liquid chromatography (HPLC) method for determining total florfenicol (FF) residues, expressed as florfenicol amine (FFA), in porcine edible tissues. The tissue homogenate were acid-hydrolyzed to liberate the bound residues and convert them into FFA. The hydrolysates were washed with ethyl acetate and subsequently extracted with ethyl acetate under alkaline conditions. The supernatants were concentrated through evaporation, defatted with hexane, purified by TLC and analyzed by HPLC at 225 nm. The optimal developing solvent for TLC purification was ethyl acetate-acetone-ammonium hydroxide mixtures (2:8:0.5, v/v/v). The method was fully validated according to decision 2002/657/EC, and could be used for the routine monitoring of FF residues in pig. TLC showed excellent purification efficiency, and was expected to solve the matrix interferences in veterinary drug residue analysis.

Asunto(s)

Cromatografía Líquida de Alta Presión/métodos , Cromatografía en Capa Delgada/métodos , Residuos de Medicamentos/análisis , Tianfenicol/análogos & derivados , Drogas Veterinarias/análisis , Estructuras Animales/química , Animales , Cromatografía Liquida/métodos , Carne/análisis , Porcinos , Tianfenicol/análisis

RESUMEN

Sodium alginate (SA) is a marine-derived biocompatible polysaccharide with huge reserves and polyisobutylene (PIB) is a saturated elastomer with gas barrier property, bio-inertness, and biocompatibility. Herein, we developed the biomass-based ASA-g-(THF5-b-PIB) graft copolymer/Ag (3-11 nm, 0.7-3.8%) nanocomposites formed in-situ via combination of transition of terminal groups in PIB chains with grafting-onto method. The above graft copolymers exhibit microphase separation by self-assembly for the difference in chemical structure from backbone and branches and annealing process as well. The crystallization morphology from backbone depends on the Mn,PIB and GN, changing from thin strip to rod-like crystal. The pH sensitivity happens in drug release behavior of ASA-g-(THF5-b-PIB) micelles, which reach 100% of drug-release within 40 h at pH = 7.4. The ASA-g-(THF5-b-PIB)/Ag composites behave good antibacterial properties to both E. coli and S. aureus and anti-protein adsorption performance. This novel graft copolymer with comprehensive properties and would have a prospect in biomedical field.

RESUMEN

Overexpression of erythroblastosis virus E26 oncogene homolog 1 (ETS1) gene is correlated with both tumor progression and poor response to chemotherapy in cancer treatment, and the exploitation of RNA interference (RNAi) technology to downregulate ETS1 seems to be a promising approach to reverse multidrug-resistant cancer cells to chemotherapy. Hence, the RNAi-based nanomedicine which is able to simultaneously downregulate ETS1 expression and to deliver chemotherapeutic agents may improve multidrug-resistant cancer therapy synergistically. In this study, we developed a supramolecular nanoassembly that could deliver siRNA targeting ETS1 (siETS1) and doxorubicin (DOX) as an effective nanomedicine to achieve successful chemotherapy towards multidrug-resistant breast cancer. The nanotherapeutic system was prepared by loading adamantane-conjugated doxorubicin (AD) into polyethyleneimine-modified (2-hydroxypropyl)-γ-cyclodextrin (HP) through the supramolecular assembly to form AD-loaded HP (HPAD), followed by electrostatically-driven self-assembly between siETS1 and HPAD. When the HPAD/siETS1 nanoassemblies were delivered into drug-resistant MCF-7/ADR cells, the drug efflux was significantly reduced as a result of simultaneous silencing of ETS1 and MDR1 genes. Importantly, the HPAD/siETS1 nanoassembly could enhance drug residence time at tumor site, and effectively inhibit drug-resistant tumor growth due to the inhibition of angiogenesis and necrosis in tumor tissues. Western blot analysis indicated that the gene expression of both ETS1 and MDR1 in vivo was considerably downregulated after the drug-resistant tumor-bearing mouse was treated with HPAD/siETS1 nanoassemblies. This study offers a new therapeutic delivery strategy targeting ETS1 for the effective multidrug-resistant chemotherapy.

Asunto(s)

Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Proteína Proto-Oncogénica c-ets-1/genética , ARN Interferente Pequeño/administración & dosificación , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Animales , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Doxorrubicina/uso terapéutico , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Proteínas Fluorescentes Verdes/genética , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Polietileneimina/química , Proteína Proto-Oncogénica c-ets-1/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/química , ARN Interferente Pequeño/uso terapéutico , Carga Tumoral , gamma-Ciclodextrinas/química

RESUMEN

The overexpression of CD44 in cancer cells reroutes number of oncogenic pathways including the central Pi3K/Akt/NF-kB pathway leading to cancer progression and malignancy. Herein, we developed hyaluronic acid-modified poly(dl-lactic-co-glycolic acid)-poly (ethylene glycol) nanoparticles (PLGA-PEG-HA NPs) for targeted delivery of TTQ (thio-tetrazolyl analog of a clinical candidate, IC87114) to CD44 overexpressing cancer cells. The PLGA-PEG co-polymer was synthesized and characterized by NMR and FTIR. The co-polymer based nanoparticles were prepared by solvent evaporation method and hyaluronic acid (HA) was conjugated on to the nanoparticle surface via EDC/NHS chemistry. The PLGA-PEG-HA NPs had a desirable particle size (<200nm) with reduced polydispersibility and exhibited spherical shape under atomic force microscope (AFM). In vitro cytotoxicity and cellular uptake studies demonstrated higher cytotoxicity and enhanced intracellular accumulation of PLGA-PEG-HA NPs compared to PLGA-PEG NPs in high CD44 expressing MiaPaca-2 cells compared to MDA-MB-231 and MCF7 cells. At the molecular level, the PLGA-PEG-HA NPs were found to be inducing premature senescence with increase in senescence associated ß-galactosidase activity and senescence specific marker p21 expression through modulation of Pi3K/Akt/NF-kB signaling pathway in MiaPaca-2 cells. These findings collectively indicated that HA-modified nanoparticles might serve as a promising nanocarrier for site-specific drug delivery, and can be explored further to increase the therapeutic efficacy of anticancer drugs via targeting to CD44 over-expressing cancer cells.

Asunto(s)

Antineoplásicos/química , Citotoxinas/química , Receptores de Hialuranos/biosíntesis , Ácido Hialurónico/química , Nanopartículas/química , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Citotoxinas/administración & dosificación , Relación Dosis-Respuesta a Droga , Composición de Medicamentos , Humanos , Ácido Hialurónico/administración & dosificación , Ácido Láctico/administración & dosificación , Ácido Láctico/química , Células MCF-7 , Nanopartículas/administración & dosificación , Ácido Poliglicólico/administración & dosificación , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis bungeana Turcz. (C. bungeana) is one of traditionally used medicines in China and possesses various biological effects, such as anti-inflammatory, antibacterial activity and inhibition of the immune function of the host. AIM OF THE STUDY: we studied the anti-inflammatory effect and molecular mechanism involved of C. bungeana both in vitro and in vivo model system in which the inflammatory response was induced by LPS treatment. MATERIALS AND METHODS: Anti-inflammatory activity of C. bungeana was investigated by LPS-induced RAW 264.7 macrophages and BALB/c mice. The production and expression of pro-inflammatory cytokines were evaluated by Griess reagent, ELISA kits and RT-qPCR, respectively. Phosphorylation status of IκBα and p65 was illustrated by western blot assay. RESULTS: C. bungeana reduced the secretion of NO, TNF-α, IL-6 and IL-1ß through inhibiting the protein expression of iNOS, TNF-α, IL-6 and IL-1ß in vitro and in vivo. Western blot analysis suggested that C. bungeana supressed NF-κB activation via regulating the phosphorylation of IκBα and p65. Immunohistochemical assay also demostrated the histological inflammatory change in liver tissue. CONCLUSIONS: The results indicate that C. bungeana supresses the activation of NF-κB signaling pathway through inhibiting phosphorylation of IκBα and p65, which results in good anti-inflammatory effect. In addition, C. bungeana attenuates inflammatory reaction by supressing the expression of various inflammatory cytokines both in vivo and in vitro.

Asunto(s)

Corydalis/química , Inflamación/prevención & control , Lipopolisacáridos/toxicidad , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Línea Celular , Citocinas/biosíntesis , Citocinas/genética , Inflamación/inducido químicamente , Mediadores de Inflamación/metabolismo , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosforilación

RESUMEN

Chitosan, as a biocompatible polymer, is very attractive for biomedical applications. Continues studies are performing for improving its physicochemical features in order to make it more suitable for such approaches. In this study, methylated 4-N,N dimethyl aminobenzyl N,O carboxymethyl chitosan (MABCC) was synthesized,as a new chitosan derivative, in three steps. The investigations were carried out using FTIR, NMR, TGA and zeta potential measurement. Antibacterial and cell viability assessments were performed on four bacterial strains and two cell lines respectively. FTIR and NMR results showed that all substitution reactions were successfully carried out. Zeta potential of MABCC at various pH especially alkaline pH was greater than chitosan and it revealed increasing the solubility of the derivative. Antibacterial activity of MABCC was extremely greater than chitosan especially in Gram positive bacteria.Furthermore,it had no significant cytotoxicity against MCF-7 and Skov-3 cell lines in comparison to chitosan. These findings confirm that this new derivative can be introduced as a suitable compound for biomedical purposes.

Asunto(s)

Antibacterianos/síntesis química , Antibacterianos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Quitosano/química , Antibacterianos/química , Antineoplásicos/química , Técnicas de Química Sintética , Quitosano/análogos & derivados , Humanos , Células MCF-7 , Metilación

RESUMEN

For the first time, the synthesis of polymeric hydrogels containing cyclodextrins (CDs) obtained by frontal polymerization (FP) is reported. In particular, the effects of CDs on poly(2-hydroxyethylacrylate) hydrogel properties are investigated. In a first series of materials, ß-cyclodextrin is dispersed into the polymer matrix, while in the second one acryloyl-ß-cyclodextrin is grafted to poly(2-hydroxyethylacrylate) chains. FP parameters (front velocity and maximum temperature), swelling properties, glass transition temperatures and mechanical properties of the hydrogels are studied. Results show that both types of cyclodextrin influence the above properties, and the major effects are found for concentration higher than 1mol% of acryloyl-ß-cyclodextrin. Namely, a significant increase of glass transition temperature and of compression moduli are found. Finally, this study demonstrates that FP is a convenient technique to obtain CD-containing hydrogels, in which the type and amount of cyclodextrin can be suitably modulated to tune polymer properties, in function of the desired hydrogel applications.

Asunto(s)

Hidrogeles/química , Polihidroxietil Metacrilato/análogos & derivados , Polimerizacion , beta-Ciclodextrinas/química , Técnicas de Química Sintética , Fenómenos Mecánicos , Transición de Fase , Polihidroxietil Metacrilato/síntesis química , Polihidroxietil Metacrilato/química , Solubilidad

RESUMEN

A micellar liquid chromatographic method was developed for the analysis of oxolinic acid, flumequine, marbofloxacin and enrofloxacin in honey. These quinolines are unethically used in beekeeping, and a zero-tolerance policy to antibiotic residues in honey has been stated by the European Union. The sample pretreatment was a 1:1 dilution with a 0.05M SDS at pH 3 solution, filtration and direct injection, thus avoiding extraction steps. The quinolones were eluted without interferences using mobile phase of 0.05M SDS/12.5% 1-propanol/0.5% triethylamine at pH 3, running at 1mL/min under isocratic room through a C18 column. The analytes were detected by fluorescence. The method was successfully validated according to the requirements of the European Union Decision 2002/657/EC in terms of: specificity, linearity (r(2)>0.995), limit of detection and decision limit (0.008-0.070mg/kg), lower limit of quantification (0.02-0.2mg/kg), detection capability (0.010-0.10mg/kg), recovery (82.1-110.0%), precision (<9.4%), matrix effects, robustness (<10.4%), and stability. The procedure was applied to several commercial honey supplied by a local supermarket, and the studied antibiotics were not detected. Therefore, the method was rapid, simple, safe, eco friendly, reliable and useful for the routine analysis of honey samples.

Asunto(s)

Cromatografía Liquida/métodos , Fluoroquinolonas/análisis , Miel/análisis , Ácido Oxolínico/análisis , Enrofloxacina , Unión Europea , Micelas , Sensibilidad y Especificidad

RESUMEN

A prodrug-based nanosystem obtained by formulating prodrug and nanotechnology into a system is one of the most promising strategies to enhance drug delivery for disease treatment. Herein, we report a new nanosystem based on HA-PTX conjugates (HA-PTX Ns), which penetrated across cell membranes into cytosol, thus enhancing paclitaxel (PTX) delivery. HA-PTX Ns were successfully obtained based on HA-PTX, and their average particle size was approximately 200 nm. Importantly, unlike other prodrug-based nanosystems, HA-PTX Ns obtained cellular entry without entrapment within the lysosomal-endosomal system by using pathways including clathrin-mediated endocytosis, microtubule-associated internalization, macropinocytosis and cholesterol-dependence. Due to significant accumulation in tumors, HA-PTX Ns had more than a 4-fold decrease in tumor volume on day 14 in contrast with PTX alone. In conclusion, HA-PTX Ns could enter cells, bypass the lysosomal-endosomal system and improve PTX delivery.

Asunto(s)

Antineoplásicos Fitogénicos/administración & dosificación , Citosol/metabolismo , Ácido Hialurónico/química , Nanopartículas/química , Paclitaxel/administración & dosificación , Profármacos/administración & dosificación , Animales , Apoptosis , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos , Humanos , Células MCF-7 , Masculino , Ratones , Micelas , Polietilenglicoles , Ratas

RESUMEN

Gemcitabine, a nucleoside analogue, is used in the treatment of various solid tumors, however, its efficacy is limited by rapid metabolism by cytidine deaminase and fast kidney excretion. In this study, a polymeric conjugate of gemcitabine was prepared by covalent coupling with poly(lactic-co-glycolic) acid (PLGA), in order to improve anticancer efficacy of the drug. The prepared conjugate was characterized by various analytical techniques including FTIR, NMR and mass spectroscopic analysis. The stability study indicated that the polymeric conjugate was more stable in plasma as compared to native gemcitabine. Further, in vitro cytotoxicity determined in a panel of cell lines including pancreatic cancer (MIAPaCa-2), breast cancer (MCF-7) and colon cancer (HCT-116), indicated that the cytotoxic activity of gemcitabine was retained following conjugation with polymeric carrier. In the nucleoside transportation inhibition assay, it was found that the prepared conjugate was not dependent on nucleoside transporter for entering into the cells and this, in turn, reflecting potential implication of this conjugate in the therapy of transporter- deficient resistance cancer. Further, the cell cycle analysis showed that the sub-G1 (G0) apoptotic population was 46.6% and 60.6% for gemcitabine and PLGA gemcitabine conjugate, respectively. The conjugate produced remarkable decrease in mitochondrial membrane potential, a marker of apoptosis. In addition, there was a marked increase in PARP cleavage and P-H2AX expression with PLGA gemcitabine conjugate as compared to native gemcitabine indicating improved apoptotic activity. The findings demonstrated the potential of PLGA gemcitabine conjugate to improve clinical outcome of gemcitabine based chemotherapy of cancer.

Asunto(s)

Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/química , Desoxicitidina/análogos & derivados , Ácido Láctico/administración & dosificación , Ácido Láctico/química , Ácido Poliglicólico/administración & dosificación , Ácido Poliglicólico/química , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Desoxicitidina/administración & dosificación , Desoxicitidina/química , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteínas de Transporte de Nucleósidos/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Gemcitabina

RESUMEN

Liposomes radiolabelling with diagnostic radionuclides is an excellent tool for studying pharmacokinetics with the view of developing liposome-based drug delivery agents. The aim of the present study is to evaluate the in vitro and in vivo behavior of a (99m)Tc-labeled liposome by applying either a direct labeling strategy via a carboxyl group, LP-COOH, or a surface chelating method via pyridyl ethyl cysteine compound (with the intermediate [99mTc(I)(CO)3(H2O)(3)](+)), LP-PEC. 99mTc-LP-COOH was obtained in high radiolabelling yield and radiochemical purity, while 99mTc(I)(CO)3-LP-PEC was initially purified before being in vitro and in vivo evaluated. 99mTc-LP-COOH was less stable in the presence of competitive for 99mTc ligands than 99mTc(I)(CO)3-LP-PEC. According to DLS measurements, the presence of serum as well as the applied radiolabelling conditions did not affect the liposomes' size. The different radiolabelling methods seemed to exert an influence on the biodistribution pattern of the liposomes with the 99mTc(I)(CO)3-LP-PEC showing slow blood clearance, which was also confirmed by in vivo scintigraphic imaging. Nevertheless, passive tumor targeting was attained at a similar extent no matter which radiolabelling technique was followed.

Asunto(s)

Lípidos/química , Neoplasias/diagnóstico por imagen , Radiofármacos , Compuestos de Tecnecio , Animales , Línea Celular Tumoral , Femenino , Humanos , Inyecciones Intravenosas , Liposomas , Ratones , Neoplasias/metabolismo , Tamaño de la Partícula , Cintigrafía , Radiofármacos/administración & dosificación , Radiofármacos/síntesis química , Radiofármacos/farmacocinética , Compuestos de Tecnecio/administración & dosificación , Compuestos de Tecnecio/síntesis química , Compuestos de Tecnecio/farmacocinética , Distribución Tisular

RESUMEN

The aim of the study was to investigate the protective effect of isoniazid-curcumin conjugate (INH-CRM) in INH-induced hepatic injury by biochemical analysis and histology examination of liver in Wistar rats. The biochemical analysis included determination of the levels of plasma cholesterol, triglycerides (TG), albumin content, and lipid peroxidation (MDA). INH-CRM administration resulted in a significant decrease in plasma cholesterol, TG, and MDA levels in the liver tissue homogenate with an elevation in albumin level indicating its hepatoprotective activity. Histology of the liver further confirmed the reduction in hepatic injury. The hepatoprotective with INH-CRM can be attributed to the antioxidant activity of curcumin. The conjugate probably stabilizes the curcumin molecule, preventing its presystemic metabolism thereby enhancing its bioavailability and therefore, its hepatoprotective activity. Thus, the novel INH-CRM has the potential to alleviate INH-induced liver toxicity in antitubercular treatment.