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1.
J Nanobiotechnology ; 22(1): 547, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39238027

RESUMEN

Rheumatoid arthritis (RA) involves chronic inflammation, oxidative stress, and complex immune cell interactions, leading to joint destruction. Traditional treatments are often limited by off-target effects and systemic toxicity. This study introduces a novel therapeutic approach using hyaluronic acid (HA)-conjugated, redox-responsive polyamino acid nanogels (HA-NG) to deliver tacrolimus (TAC) specifically to inflamed joints. The nanogels' disulfide bonds enable controlled TAC release in response to high intracellular glutathione (GSH) levels in activated macrophages, prevalent in RA-affected tissues. In vitro results demonstrated that HA-NG/TAC significantly reduced TAC toxicity to normal macrophages and showed high biocompatibility. In vivo, HA-NG/TAC accumulated more in inflamed joints compared to non-targeted NG/TAC, enhancing therapeutic efficacy and minimizing side effects. Therapeutic evaluation in collagen-induced arthritis (CIA) mice revealed HA-NG/TAC substantially reduced paw swelling, arthritis scores, synovial inflammation, and bone erosion while suppressing pro-inflammatory cytokine levels. These findings suggest that HA-NG/TAC represents a promising targeted drug delivery system for RA, offering potential for more effective and safer clinical applications.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Ácido Hialurónico , Nanogeles , Péptidos , Tacrolimus , Animales , Ácido Hialurónico/química , Artritis Reumatoide/tratamiento farmacológico , Ratones , Tacrolimus/farmacología , Tacrolimus/uso terapéutico , Tacrolimus/química , Tacrolimus/farmacocinética , Artritis Experimental/tratamiento farmacológico , Péptidos/química , Péptidos/farmacología , Nanogeles/química , Masculino , Células RAW 264.7 , Sistemas de Liberación de Medicamentos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones Endogámicos DBA , Portadores de Fármacos/química , Humanos
2.
Ecotoxicol Environ Saf ; 276: 116284, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38581912

RESUMEN

Fluorosis due to high fluoride levels in drinking water profoundly affects the development of human skeletal and dental structures. Sodium butyrate (NaB) has been found to regulate overall bone mass and prevent pathological bone loss. However, the mechanism of NaB action on fluorosis remains unclear. In this study, a rat model of fluorosis induced by 100 mg/L sodium fluoride was used to investigate the impact of NaB on bone homeostasis and serum metabolomics. It was found that NaB significantly reduced the levels of bone resorption markers CTX-Ⅰ and TRACP-5B in fluorosis rats. Moreover, NaB increased calcium and magnesium levels in bone, while decreasing phosphorus levels. In addition, NaB improved various bone microstructure parameters, including bone mineral density (BMD), trabecular thickness (Tb. Th), trabecular bone separation (Tb. SP), and structural model index (SMI) in the femur. Notably, NaB intervention also enhanced the antioxidant capacity of plasma in fluorosis rats. Furthermore, a comprehensive analysis of serum metabolomics by LC-MS revealed a significant reversal trend of seven biomarkers after the intervention of NaB. Finally, pathway enrichment analysis based on differential metabolites indicated that NaB exerted protective effects on fluorosis by modulating arginine and proline metabolic pathways. These findings suggest that NaB has a beneficial effect on fluorosis and can regulate bone homeostasis by ameliorating metabolic disorders.


Asunto(s)
Ácido Butírico , Fluorosis Dental , Homeostasis , Animales , Ratas , Homeostasis/efectos de los fármacos , Ácido Butírico/farmacología , Huesos/efectos de los fármacos , Masculino , Densidad Ósea/efectos de los fármacos , Biomarcadores/sangre , Ratas Sprague-Dawley , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Resorción Ósea/inducido químicamente , Fluoruro de Sodio/toxicidad
3.
Pestic Biochem Physiol ; 204: 106082, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39277395

RESUMEN

Bemisia tabaci poses a severe threat to plants, and the control of B. tabaci mainly relies on pesticides, which causes more and more rapidly increasing resistance. ß-Caryophyllene is a promising ingredient for agricultural pest control, but its feature of poor water solubility need to be improved in practical applications. Nanotechnology can enhance the effectiveness and dispersion of volatile organic compounds (VOCs). In this study, a nanoliposome carrier was constructed by ethanol injection and ultrasonic dispersion method, and ß-caryophyllene was wrapped inside it, thus solving the defect of poor solubility of ß-caryophyllene. The size of the ß-caryophyllene nanoliposomes (C-BT-NPs) was around 200 nm, with the absolute value of the zeta potential exceeding 30 mV and a PDI below 0.5. The stability was also maintained over a 14-d storage period. C-BT-NPs showed effective insecticidal activity against B. tabaci, with an LC50 of 1.51 g/L, outperforming thiamethoxam and offering efficient agricultural pest control. Furthermore, C-BT-NPs had minimal short-term impact on the growth of tomato plants, indicating that they are safety on plants. Therefore, the VOCs using nanoliposome preparation technology show promise in reducing reliance on conventional pesticides and present new approaches to managing agricultural pests.


Asunto(s)
Hemípteros , Insecticidas , Liposomas , Sesquiterpenos Policíclicos , Animales , Hemípteros/efectos de los fármacos , Sesquiterpenos Policíclicos/farmacología , Sesquiterpenos Policíclicos/química , Insecticidas/farmacología , Insecticidas/química , Nanopartículas/química , Sesquiterpenos/farmacología , Sesquiterpenos/química , Solanum lycopersicum/parasitología , Compuestos Orgánicos Volátiles/química , Compuestos Orgánicos Volátiles/farmacología
4.
Macromol Rapid Commun ; 44(4): e2200720, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36621912

RESUMEN

Response to external stimuli plays a significant role in the environmental adaptation of living matters and intelligent devices. Most stimulus-response systems in nature can respond to appropriate stimuli, and inhibit the response under excessive stimuli, such as excessive heat or water, which can be called overload protection. However, even though various responsive materials have been developed for different stimuli, most of them are not protective against the overload stimuli. In this work, a bilayer actuator based on semicrystalline polyurethane is designed, which can respond differently to proper stimuli and excessive stimuli, i.e., water. This actuator can bend gradually under the proper stimulation of water, but will straighten and even bend reversely with excessive stimulation. The mechanism behind the reversible and adjustable actuator with overload protection is investigated both experimentally and theoretically, and the competition between dynamic factors and thermodynamic stability in the swelling process is considered the main cause.


Asunto(s)
Poliuretanos , Agua , Termodinámica , Calor
5.
Med Sci Monit ; 29: e940134, 2023 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-37461206

RESUMEN

BACKGROUND Percutaneous vertebral augmentation is the mainstream treatment of osteoporotic vertebral compression fracture (OVCF). New vertebral compression fracture (NVCF) after percutaneous vertebral augmentation may be an issue that cannot be ignored. Nevertheless, the risk factors for NVCF are still uncertain. This research aimed to study the risk factors for NVCF after percutaneous vertebral augmentation. MATERIAL AND METHODS All patients who underwent percutaneous vertebral augmentation for OVCF from January 2019 to December 2020 were enrolled in the study. These patients were divided into NVCF and control groups according to whether they had NVCF. The covariates including sex, age, BMI, diabetes, hypertension, smoking, alcohol, fracture level, surgical method, cement leakage, cement volume, preoperative anterior vertebral height ratio, and Hounsfield unit (HU) value were reviewed. Univariate and multivariate analyses were performed to identify risk factors. RESULTS A total of 279 patients were included in this study, of which 47 had NVCF after percutaneous vertebral augmentation. Univariate analysis demonstrated that there were significant differences in age (OR=1.040, 95% CI=1.003-1.078, P=0.033), BMI (OR=0.844, 95% CI=0.758-0.939, P=0.002) and HU value (OR=0.945, 95% CI=0.929-0.962, P<0.001) between the 2 groups. Multivariate regression analysis revealed that HU value (OR=0.942, 95% CI=0.924-0.960, P<0.001) were independent risk factor for NVCF after percutaneous vertebral augmentation. CONCLUSIONS Hounsfield unit value was an independent risk factor for new vertebral compression fracture after percutaneous vertebral augmentation, whereas age and BMI were not.


Asunto(s)
Fracturas por Compresión , Cifoplastia , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Vertebroplastia , Humanos , Fracturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/tratamiento farmacológico , Fracturas por Compresión/cirugía , Fracturas por Compresión/etiología , Estudios Retrospectivos , Cifoplastia/efectos adversos , Cifoplastia/métodos , Resultado del Tratamiento , Vertebroplastia/efectos adversos , Vertebroplastia/métodos , Cementos para Huesos/efectos adversos , Factores de Riesgo , Fracturas Osteoporóticas/cirugía , Fracturas Osteoporóticas/etiología
6.
Biomacromolecules ; 19(3): 980-988, 2018 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-29451778

RESUMEN

To meet the progressive requirements of advanced engineering materials with superior physicochemical performances, self-healing and injectable hydrogels (AD hydrogels) based on agarose with pH-response were prepared through dynamic covalent Schiff-base linkages by simply mixing nontoxic agarose-ethylenediamine conjugate (AG-NH2) and dialdehyde-functionalized polyethylene glycol (DF-PEG) solutions. The self-healing and injectable capabilities of the hydrogels without any external stimulus are ascribed to dynamic covalent Schiff-base linkages between the aldehyde groups of DF-PEG and amine groups on AG-NH2 backbone. It is demonstrated that the AD hydrogels possess interconnected porous morphologies, rapid gelation time, excellent deformability, and good mechanical strength. The incorporated Schiff's base imparts the hydrogels to the remarkable tissue adhesiveness. In vivo hemostatic tests on rabbit liver demonstrate that the hydrogels are able to stanch the severe trauma effectively. Compared with the conventional gauze treatment, the total amount of bleeding sharply declined to be (0.19 ± 0.03) g, and hemostasis time was strikingly shorter than 10 s after treating with AD hydrogels. In summary, the self-healing ability, cytocompatibility, and adhesion characteristic of the pH-responsive hydrogels make them promising candidates for long-lived wound dressings in critical situations.


Asunto(s)
Vendajes , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Hidrogeles , Sefarosa , Adhesivos Tisulares , Heridas y Lesiones/terapia , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Sefarosa/química , Sefarosa/farmacología , Adhesivos Tisulares/química , Adhesivos Tisulares/farmacología , Heridas y Lesiones/metabolismo , Heridas y Lesiones/patología
7.
Sci Rep ; 14(1): 10679, 2024 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724534

RESUMEN

The supercritical antisolvent (SAS) process was a green alternative to improve the low bioavailability of insoluble drugs. However, it is difficult for SAS process to industrialize with limited production capacity. A coaxial annular nozzle was used to prepare the microcapsules of aprepitant (APR) and polyvinylpyrrolidone (PVP) by SAS with N, N-Dimethylformamide (DMF) as solvent. Meanwhile, the effects of polymer/drug ratio, operating pressure, operating temperature and overall concentration on particles morphology, mean particle diameter and size distribution were analyzed. Microcapsules with mean diameters ranging from 2.04 µm and 9.84 µm were successfully produced. The morphology, particle size, thermal behavior, crystallinity, drug content, drug dissolution and residual amount of DMF of samples were analyzed. The results revealed that the APR drug dissolution of the microcapsules by SAS process was faster than the unprocessed APR. Furthermore, the drug powder collected every hour is in the kilogram level, verifying the possibility to scale up the production of pharmaceuticals employing the SAS process from an industrial point of view.


Asunto(s)
Aprepitant , Cápsulas , Tamaño de la Partícula , Povidona , Solventes , Cápsulas/química , Povidona/química , Solventes/química , Aprepitant/química , Solubilidad , Dimetilformamida/química , Liberación de Fármacos , Composición de Medicamentos/métodos , Temperatura
8.
Water Res ; 249: 120890, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38016222

RESUMEN

Emerging electrochemical disinfection techniques provide a promising pathway to the biofouling control of reverse osmosis (RO) process. However, the comparative effectiveness and mechanism of it under flow-through conditions with low voltage remains unclear. This study investigated the effect of a flow-through electrode system (FES) with both direct current (DC) and alternating pulse current (AC) on RO biofouling control compared with chlorine disinfection. At the initial stage of biofouling development, the normalized flux of AC-FES (67% on Day 5) was saliently higher than the control group (56% on Day 5). Subsequently, the normalized fluxes of each group tended similarity in their differences until the 20th day. After mild chemical cleaning, the RO membrane in the AC-FES group reached the highest chemical cleaning efficiency of 58%, implying its foulant was more readily removable and the biofouling was more reversible. The biofouling layer in the DC-FES group was also found to be easily cleanable. Morphological analysis suggested that the thickness and compactness of the fouling layers were the major reasons for the fouling behavior difference. The abundance of 4 fouling-related abundant genera (>1%), which were Pseudomonas, Thiobacillus, Sphingopyxis, and Mycobacterium exhibited a salient correlation with the biofouling degree. The operating cost of FES was also lower than that of chlorine disinfection. In summary, AC-FES is a promising alternative to chlorine disinfection in RO biofouling control, as it caused less and easy-cleaning biofouling layer mainly due to two advantages: a) reducing the regrowth potential after disinfection of the bacteria, leading to alleviated initial fouling, (b) reshaping the microbial community to those with weaker biofilm formation capacity.


Asunto(s)
Incrustaciones Biológicas , Purificación del Agua , Aguas Residuales , Incrustaciones Biológicas/prevención & control , Cloro , Membranas Artificiales , Ósmosis , Purificación del Agua/métodos
9.
ACS Appl Bio Mater ; 5(4): 1670-1682, 2022 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-35294185

RESUMEN

Nearly 20% of HER2-positive breast cancers develop resistance to HER2-targeted therapies requiring the use of advanced therapies. Silencing RNA therapy may be a powerful modality for treating resistant HER2 cancers due to its high specificity and low toxicity. However, the systemic administration of siRNAs requires a safe and efficient delivery platform because of siRNA's low stability in physiological fluids, inefficient cellular uptake, immunoreactivity, and rapid clearance. We have developed theranostic polymeric vesicles to overcome these hurdles for encapsulation and delivery of small functional molecules and PARP1 siRNA for in vivo delivery to breast cancer tumors. The 100 nm polymer vesicles were assembled from biodegradable and non-ionic poly(N-vinylpyrrolidone)14-block-poly(dimethylsiloxane)47-block-poly(N-vinylpyrrolidone)14 triblock copolymer PVPON14-PDMS47-PVPON14 using nanoprecipitation and thin-film hydration. We demonstrated that the vesicles assembled from the copolymer covalently tagged with the Cy5.5 fluorescent dye for in vivo imaging could also encapsulate the model drug with high loading efficiency (40%). The dye-loaded vesicles were accumulated in tumors after 18 h circulation in 4TR breast tumor-bearing mice via passive targeting. We found that PARP1 siRNA encapsulated into the vesicles was released intact (13%) into solution by the therapeutic ultrasound treatment as quantified by gel electrophoresis. The PARP1 siRNA-loaded polymersomes inhibited the proliferation of MDA-MB-361TR cells by 34% after 6 days of treatment by suppressing the NF-kB signaling pathway, unlike their scrambled siRNA-loaded counterparts. Finally, the treatment by PARP1 siRNA-loaded vesicles prolonged the survival of the mice bearing 4T1 breast cancer xenografts, with the 4-fold survival increase, unlike the untreated mice after 3 weeks following the treatment. These biodegradable, non-ionic PVPON14-PDMS47-PVPON14 polymeric nanovesicles capable of the efficient encapsulation and delivery of PARP1 siRNA to successfully knock down PARP1 in vivo can provide an advanced platform for the development of precision-targeted therapeutic carriers, which could help develop highly effective drug delivery nanovehicles for breast cancer gene therapy.


Asunto(s)
Neoplasias de la Mama , Animales , Neoplasias de la Mama/tratamiento farmacológico , Dimetilpolisiloxanos , Femenino , Humanos , Ratones , Poli(ADP-Ribosa) Polimerasa-1/genética , Polímeros , Pirrolidinonas , ARN Interferente Pequeño/genética
10.
Int J Nanomedicine ; 17: 227-244, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35068931

RESUMEN

INTRODUCTION: (-)-Gossypol (AT-101), the (-)-enantiomer of the natural compound gossypol, has shown significant inhibitory effects on various types of cancers such as osteosarcoma, myeloma, glioma, lung cancer, and prostate cancer. However, the clinical application of (-)-gossypol was often hindered by its evident side effects and the low bioavailability via oral administration, which necessitated the development of suitable (-)-gossypol preparations to settle the problems. In this study, injectable cyclic RGD (cRGD)-decorated liposome (cRGD-LP) was prepared for tumor-targeted delivery of (-)-gossypol. METHODS: The cRGD-LP was prepared based on cRGD-modified lipids. For comparison, a non-cRGD-containing liposome (LP) with a similar chemical composition to cRGD-LP was specially designed. The physicochemical properties of (-)-gossypol-loaded cRGD-LP (Gos/cRGD-LP) were investigated in terms of the drug loading efficiency, particle size, morphology, drug release, and so on. The inhibitory effect of Gos/cRGD-LP on the proliferation of tumor cells in vitro was evaluated using different cell lines. The biodistribution of cRGD-LP in vivo was investigated via the near-infrared (NIR) fluorescence imaging technique. The antitumor effect of Gos/cRGD-LP in vivo was evaluated in PC-3 tumor-bearing nude mice. RESULTS: Gos/cRGD-LP had an average particle size of about 62 nm with a narrow size distribution, drug loading efficiency of over 90%, and sustained drug release for over 96 h. The results of NIR fluorescence imaging demonstrated the enhanced tumor targeting of cRGD-LP in vivo. Moreover, Gos/cRGD-LP showed a significantly enhanced inhibitory effect on PC-3 tumors in mice, with a tumor inhibition rate of over 74% and good biocompatibility. CONCLUSION: The incorporation of cRGD could significantly enhance the tumor-targeting effect of the liposomes and improve the antitumor effect of the liposomal (-)-gossypol in vivo, which indicated the potential of Gos/cRGD-LP that warrants further investigation for clinical applications of this single-isomer drug.


Asunto(s)
Gosipol , Liposomas , Animales , Línea Celular Tumoral , Gosipol/análogos & derivados , Masculino , Ratones , Ratones Desnudos , Péptidos Cíclicos , Distribución Tisular
11.
Bioresour Technol ; 337: 125392, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34130232

RESUMEN

To improve the utilization efficiency of corn stover , steam explosion pretreatment and cellulase/lactic acid bacteria-assisted ensilage storage were conducted in sequence, mainly focusing on morphological structure, lignocellulose fraction, cellulose accessibility and degradation profile. The results showed that there was a synergistic effect of steam explosion and ensilage storage, where hemicellulose of corn stover was partly degraded during steam explosion processing (70%) or ensilage storage (20-40%). Meanwhile, its morphological structure was apparently broken, increasing cellulose accessibility (2.44, 2.83, 4.08-4.33 mg/g), where enzyme YDL and inoculant QZB were the two most effective additives. Furthermore, rumen effective degradability of corn stover (39.25%, 48.33%, 52.57-54.07%) were increased along with greater rapid degradation fraction (0, 1.67%, 9.16-11.62%) and degradation rate of slow degradation fraction (0.020, 0.034, 0.039-0.048 h-1) . In conclusions, it is suggested that treating corn stover with steam explosion processing and ensilage storage is a feasible way to improve its utilization efficiency.


Asunto(s)
Celulasa , Lactobacillales , Animales , Celulosa , Hidrólisis , Vapor , Zea mays
12.
Ann Transl Med ; 9(21): 1622, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34926666

RESUMEN

BACKGROUND: The aim of this study was to explore the value of using the YOLOv3 algorithm for detection and diagnosis of dental caries in oral photographs taken with mobile phones. METHODS: Oral photographs taken with the mobile phones of 570 patients were used as 3 datasets: the augmented images (n=3,990), the enhanced images (n=3,990), and the combined augmented and enhanced images (n=7,980). Oral photographs taken by mobile phones from another 70 patients were used as an independent test set. We used the YOLOv3 network for migration learning for modelling. Diagnostic precision, recall, F1-score, and mean average precision (mAP) were calculated to obtain the detection and diagnostic performance of the YOLOv3 algorithm. RESULTS: After 3 independent training, the mAP value of the original group YOLOv3 algorithm was 56.20%, in which the precision for primary caries recognition was 76.92%, recall was 49.59%, and F1-score was 0.60; the precision for secondary caries recognition was 91.67%, recall was 52.38%, and F1-score was 0.67. The mAP value of the enhance group algorithm was 66.69%, in which the precision for primary caries identification was 81.82%, recall was 52.07%, and F1-score was 0.64, and the precision for secondary caries identification was 100%, recall was 33.33%, and F1-score was 0.50. The mAP value of the comprehensive group algorithm was 85.48%, in which the precision for primary caries identification was 93.33%, recall was 69.42%, F1-score was 0.80, and the F1-score for secondary caries identification was 0.50; precision was 100%, recall was 52.38%, and F1-score was 0.69. CONCLUSIONS: The caries detection capability based on the YOLOv3 algorithm highlights the potential utility of deep learning in caries detection and diagnosis. Comparing the 3 experiments, the detection of the model trained after using image augmented and enhancement techniques was significantly improved.

13.
J Hazard Mater ; 414: 125513, 2021 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-34030404

RESUMEN

The controlled release of pesticides based on nanoparticle platforms has emerged as a new technology for increasing the efficiency of pesticides and for reducing environmental pollution because of their size-dependent and target-modifying properties. In the present study, pH/cellulase dual stimuli-responsive controlled-release formulations (PYR-HMS-HPC) were designed by grafting hydroxypropyl cellulose onto pyraclostrobin-loaded hollow mesoporous silica nanoparticles via an ester linkage. The PYR-HMS-HPC formulations were characterized by Fourier transform infrared spectroscopy, thermogravimetric analyzer, transmission electron microscope and scanning electron microscope. The results demonstrated that PYR-HMS-HPC with a loading capacity of 12.1 wt% showed excellent pyraclostrobin release behaviors in response to acidic environments and the introduction of cellulase, could effectively prevented pyraclostrobin from photolysis. Compared with commercial pyraclostrobin formulations, the PYR-HMS-HPC formulations showed much stronger and statistically significant fungicidal activity against Magnaporthe oryzae from 7 to 21 days. Furthermore, the Allium cepa chromosome aberration assay demonstrated that the PYR-HMS-HPC formulations reduced the genotoxicity of pyraclostrobin. These pH/cellulase dual stimuli-responsive controlled-release formulations are of great interest for sustainable on-demand crop disease protection.


Asunto(s)
Fungicidas Industriales , Nanopartículas , Ascomicetos , Celulosa/análogos & derivados , Portadores de Fármacos , Porosidad , Dióxido de Silicio
14.
PLoS One ; 12(3): e0173172, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28334044

RESUMEN

Bletilla striata polysaccharides (BSPs) have been used in pharmaceutical and biomedical industry, the aim of the present study was to explore a BSPs amphiphilic derivative to overcome its application limit as poorly water-soluble drug carriers due to water-soluble polymers. Stearic acid (SA) was selected as a hydrophobic block to modify B. striata polysaccharides (SA-BSPs). Docetaxel (DTX)-loaded SA-BSPs (DTX-SA-BSPs) copolymer micelles were prepared and characterized. The DTX release percentage in vitro and DTX concentration in vivo was carried out by using high performance liquid chromatography. HepG2 and HeLa cells were subjected to MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazonium bromide) assay to evaluate the cell viability. In vitro evaluation of copolymer micelles showed higher drug encapsulation and loading capacity. The release percentage of DTX from DTX-SA-BSPs copolymer micelles and docetaxel injection was 66.93 ± 1.79% and 97.06 ± 1.56% in 2 days, respectively. The DTX-SA-BSPs copolymer micelles exhibited a sustained release of DTX. A 50% increase in growth inhibition was observed for HepG2 cells treated with DTX-SA-BSPs copolymer micelles as compared to those treated with docetaxel injection for 72 h. DTX-SA-BSPs copolymer micelles presented a similar growth inhibition effect on Hela cells. Furthermore, absolute bioavailability of DTX-SA-BSPs copolymer micelles was shown to be 1.39-fold higher than that of docetaxel injection. Therefore, SA-BSPs copolymer micelles may be used as potential biocompatible polymers for cancer chemotherapy.


Asunto(s)
Polímeros/química , Polisacáridos/química , Ácidos Esteáricos/química , Taxoides/química , Taxoides/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Docetaxel , Portadores de Fármacos/química , Células HeLa , Células Hep G2 , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Micelas , Solubilidad
15.
Drug Deliv ; 23(5): 1830-7, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26652055

RESUMEN

CONTEXT: Doxorubicin (DOX)-loaded folate-targeted poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) [P(HB-HO)] nanoparticles [DOX/FA-PEG-P(HB-HO) NPs] have potential application in clinical treatments for cervical cancer due to specific affinity of folate and folate receptor in HeLa cells. OBJECTIVE: The aim of this study was to develop an optimized formulation for DOX/FA-PEG-P(HB-HO) NPs, and investigate the targeting and efficacies of the nanoparticles. MATERIALS AND METHODS: DOX/FA-PEG-P(HB-HO) NPs were prepared by W1/O/W2 solvent extraction/evaporation method, and an orthogonal experimental design [L9 (3(4))] was applied to establish the optimum conditions. The physico-chemical characteristics, microscopic observation and in vivo antitumor study of the nanoparticles were evaluated. RESULTS: The optimum formulation was obtained with DOX 10% (w/v), FA-PEG-P(HB-HO) 6.5% (w/v), PVA 3%(w/v) and oil phase/internal water phase volume ratio of 3/1. The size distribution, drug loading and encapsulation efficiency of the optimized nanoparticles were 150-350 nm, 29.6 ± 2.9% and 83.5 ± 5.7%, respectively. In vitro release study demonstrated that 80% of the drug could release from the nanoparticles within 11 days. Furthermore, in vitro microscopic observation and in vivo antitumor study showed that DOX/FA-PEG-P(HB-HO) NPs could inhibit HeLa cells effectively, and the tumor inhibition rate (TIR) in vivo was 76.91%. DISCUSSION AND CONCLUSIONS: DOX/FA-PEG-P(HB-HO) NPs have been successfully developed and optimized. In vitro drug release study suggested a sustained release profile. Moreover, DOX/FA-PEG-P(HB-HO) NPs could effectively inhibit HeLa cells with satisfying targeting, and reduce side effects and toxicity to normal tissues. DOX/FA-PEG-P(HB-HO) NPs were superior in terms of inhibiting HeLa tumor over non-targeted formulations therapy.


Asunto(s)
Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Doxorrubicina/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos/efectos de los fármacos , Nanopartículas/química , Poliésteres/química , Antineoplásicos/química , Química Farmacéutica , Doxorrubicina/química , Ácido Fólico/administración & dosificación , Ácido Fólico/química , Células HeLa , Humanos
16.
Sci Rep ; 5: 12549, 2015 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-26224622

RESUMEN

Pain caused by acute pulpitis (AP) is a common symptom in clinical settings. However, its underlying mechanisms have largely remained unknown. Using AP model, we demonstrated that dental injury caused severe pulp inflammation with up-regulated serum IL-1ß. Assessment from head-withdrawal reflex thresholds (HWTs) and open-field test demonstrated nociceptive response at 1 day post injury. A consistent up-regulation of Toll-like receptor 4 (TLR4) in the trigeminal ganglion (TG) ipsilateral to the injured pulp was found; and downstream signaling components of TLR4, including MyD88, TRIF and NF-κB, and cytokines such as TNF-α and IL-1ß, were also increased. Retrograde labeling indicated that most TLR4 positve neuron in the TG innnervated the pulp and TLR4 immunoreactivity was mainly in the medium and small neurons. Double labeling showed that the TLR4 expressing neurons in the ipsilateral TG were TRPV1 and CGRP positive, but IB4 negative. Furthermore, blocking TLR4 by eritoran (TLR4 antagonist) in TGs of the AP model significantly down-regulated MyD88, TRIF, NF-κB, TNF-α and IL-1ß production and behavior of nociceptive response. Our findings suggest that TLR4 signaling in TG cells, particularly the peptidergic TRPV1 neurons, plays a key role in AP-induced nociception, and indicate that TLR4 signaling could be a potential therapeutic target for orofacial pain.


Asunto(s)
Neuronas/metabolismo , Nocicepción , Pulpitis/patología , Receptor Toll-Like 4/metabolismo , Ganglio del Trigémino/citología , Animales , Pulpa Dental/metabolismo , Pulpa Dental/patología , Disacáridos/farmacología , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Inmunohistoquímica , Interleucina-1beta/sangre , Interleucina-1beta/metabolismo , Masculino , Microscopía Fluorescente , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/metabolismo , Neuronas/citología , Nocicepción/efectos de los fármacos , Pulpitis/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Fosfatos de Azúcar/farmacología , Receptor Toll-Like 4/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 22(6): 1060-4, 2002 Dec.
Artículo en Zh | MEDLINE | ID: mdl-12914200

RESUMEN

Liposome is one of the major areas of interest in recent years because of its many potential applications. In this paper, three phase states of liposome (micelle, lamellar and reversed hexagonal) were prepared by thin-film hydration method and their structures were observed with electron microscope. We studied the interaction between these phase states and various dyes by UV-visible spectra. As a result, the phase states of liposome can be detected by the color change or the spectroscopic change. Through careful selection, 4 kinds of useful dyes were found to detect different liposome structures, that is 2,6-dichloroindophenol sodium, congred, pinacyanol chloride and calcein. The possible mechanism of the interaction between the phases of liposome and dyes was discussed. The liposome undertakes hydrolysis and forms mixed micelle. The hydrolysis rate of lamellar is faster than that of reversed hexagonal, which makes pH of the solution to decrease and causes a color change of the dyes in a short time. This method can be applied to the separation of natural phosphatides and monitor in the production of liposome.


Asunto(s)
2,6-Dicloroindofenol/química , Colorantes/química , Liposomas/química , Absorción , Carbocianinas/química , Interacciones Farmacológicas , Fluoresceínas/química , Transición de Fase , Espectrofotometría Ultravioleta/métodos
18.
J Colloid Interface Sci ; 432: 135-43, 2014 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-25086387

RESUMEN

Circulating tumor cells (CTC) capture is one of the most effective approaches in diagnosis and treatment of cancers in the field of personalized cancer medicine. In our study, zwitterionic carboxybetaine methacrylate (CBMA) oligomers were grafted onto nylon via atomic transfer random polymerization (ATRP) which would serve as a novel material for the development of convenient CTC capture interventional medical devices. The chemical, physical and biological properties of pristine and modified nylon surfaces were assessed by Fourier transform infrared spectra, atomic force microscope, water contact angle measurements, X-ray photoelectron spectroscopy, protein adsorption, platelet adhesion, and plasma recalcification time (PRT) determinations, etc. The results, including the significant decrease of proteins adsorption and platelets adhesion, as well as prolonged PRTs demonstrated the extraordinary biocompatibility and blood compatibility of the modified surface. Furthermore, we showed that upon immobilization of anti-epithelial cell adhesion molecular (anti-EpCAM) antibody onto the CBMA moiety, the modified nylon surface can selectively capture EpCAM positive tumor cells from blood with high efficiency, indicating the potential of the modified nylon in the manufacture of convenient interventional CTC capture medical devices.


Asunto(s)
Anticuerpos Antineoplásicos/química , Antígenos de Neoplasias/química , Moléculas de Adhesión Celular/química , Metacrilatos/química , Proteínas de Neoplasias/química , Células Neoplásicas Circulantes , Nylons/química , Neoplasias Gástricas , Antígenos de Neoplasias/metabolismo , Moléculas de Adhesión Celular/metabolismo , Línea Celular Tumoral , Molécula de Adhesión Celular Epitelial , Humanos , Proteínas de Neoplasias/metabolismo , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia
19.
Int J Environ Res Public Health ; 11(1): 1020-33, 2014 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-24419046

RESUMEN

Anthocyanins are polyphenols and well known for their biological antioxidative benefits. Maize purple plant pigment (MPPP) extracted and separated from maize purple plant is rich in anthocyanins. In the present study, MPPP was used to alleviate the adverse effects generated by fluoride on liver and kidney in rats. The results showed that the ultrastructure of the liver and kidney in fluoride treated rats displayed shrinkage of nuclear and cell volume, swollen mitochondria and endoplasmic reticulum and vacuols formation in the liver and kidney cells. MPPP significantly attenuated these fluoride-induced pathological changes. The MDA levels in serum and liver tissue of fluoride alone treated group were significantly higher than those of the control group (p < 0.05). The presence of 5 g/kg MPPP in the diet reduced the elevation of MDA levels in blood and liver, and increased the SOD and GSH-Px activities in kidney and GSH level in liver and kidney compared with the fluoride alone treated group (p < 0.05). In addition, MPPP alleviated the decrease of Bcl-2 protein expression and the increase of Bax protein expression induced by fluoride. This study demonstrated the protective role of MPPP against fluoride-induced oxidative stress in liver and kidney of rats.


Asunto(s)
Antocianinas/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Intoxicación por Flúor/prevención & control , Animales , Antocianinas/aislamiento & purificación , Antocianinas/farmacología , Antioxidantes/metabolismo , Evaluación Preclínica de Medicamentos , Femenino , Fluoruros/metabolismo , Fluorosis Dental/prevención & control , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/ultraestructura , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/ultraestructura , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Zea mays/química , Proteína X Asociada a bcl-2/metabolismo
20.
Colloids Surf B Biointerfaces ; 121: 238-47, 2014 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-25016426

RESUMEN

In-stent restenosis (ISR) and re-endothelialization delay are two major issues of intravascular stent in terms of clinical safety and effects. Construction of mimetic cell membrane surface on stents using phosphorylcholine have been regarded as one of the most powerful strategies to resolve these two issues and improve the performance of stents. In this study, atomic layer deposition (ALD) technology, which is widely used in semiconductor industry, was utilized to fabricate ultra-thin layer (10nm) of alumina (Al2O3) on 316L stainless steel (SS), then the alumina covered surface was modified with 3-aminopropyltriethoxysilane (APS) and 2-methacryloyloxyethyl phosphorylcholine (MPC) sequentially in order to produce phosphorylcholine mimetic cell membrane surface. The pristine and modified surfaces were characterized using X-ray photoelectron spectroscopy, atomic force microscope and water contact angle measurement. Furthermore, the abilities of protein adsorption, platelet adhesion and cell proliferation on the surfaces were investigated. It was found that alumina layer can significantly enhance the surface grafting of APS and MPC on SS; and in turn efficiently inhibit protein adsorption and platelet adhesion, and promote the attachment and proliferation of human umbilical vein endothelial cells (HUVEC) on the surfaces. In association with the fact that the deposition of alumina layer is also beneficial to the improvement of adhesion and integrity of drug-carrying polymer coating on drug eluting stents, we expect that ALD technology can largely assist in the modifications on inert metallic surfaces and benefit implantable medical devices, especially intravascular stents.


Asunto(s)
Ensayo de Materiales/métodos , Metacrilatos/química , Fosforilcolina/análogos & derivados , Acero Inoxidable/farmacología , Stents , Adsorción , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Materiales Biocompatibles Revestidos/farmacología , Fibrinógeno/metabolismo , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Imagenología Tridimensional , Ácido Láctico/química , Microscopía de Fuerza Atómica , Microscopía Electrónica de Rastreo , Fosforilcolina/química , Espectroscopía de Fotoelectrones , Adhesividad Plaquetaria/efectos de los fármacos , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico
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