Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Fa Yi Xue Za Zhi ; 40(2): 149-153, 2024 Apr 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-38847029

RESUMEN

OBJECTIVES: To investigate the age-related changes of the mandibular third molar root pulp visibility in individuals in East China, and to explore the feasibility of applying this method to determine whether an individual is 18 years or older. METHODS: A total of 1 280 oral panoramic images were collected from the 15-30 years old East China population, and the mandibular third molar root pulp visibility in all oral panoramic images was evaluated using OLZE 0-3 four-stage method, and the age distribution of the samples at each stage was analyzed using descriptive statistics. RESULTS: Stages 0, 1, 2 and 3 first appeared in 16.88, 19.18, 21.91 and 25.44 years for males and in 17.47, 20.91, 22.01 and 26.01 years for females. In all samples, individuals at stages 1 to 3 were over 18 years old. CONCLUSIONS: It is feasible to determine whether an individual in East China is 18 years or older based on the mandibular third molar root pulp visibility on oral panoramic images.


Asunto(s)
Determinación de la Edad por los Dientes , Pulpa Dental , Tercer Molar , Radiografía Panorámica , Raíz del Diente , Humanos , Tercer Molar/diagnóstico por imagen , Masculino , Adolescente , Femenino , Adulto , Adulto Joven , China , Raíz del Diente/diagnóstico por imagen , Determinación de la Edad por los Dientes/métodos , Pulpa Dental/diagnóstico por imagen , Mandíbula/diagnóstico por imagen , Odontología Forense/métodos , Factores de Edad
2.
J Nanobiotechnology ; 21(1): 379, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37848975

RESUMEN

BACKGROUND: Brain-derived neurotrophic factor (BDNF) with neuronic development and function is a promising therapeutic agent for treating depressive disorder, according to the neurotrophin hypothesis. However, the delivery of BDNF into the brain is not easy as these large protein molecules cannot efficiently cross the blood-brain barrier (BBB) and easily suffer oxidative damage in vivo. Therefore, the quercetin-based alginate nanogels (quercetin nanogels) loaded with BDNF have been developed, which could efficiently bypass the BBB via the nose-to-brain pathway and protect BDNF from oxidative damage, providing an effective route for the therapy of depressive disorders by intranasal delivery. RESULTS: Quercetin nanogels exhibited uniform size distribution, excellent biocompatibility, and potent antioxidant and anti-inflammatory activities. Quercetin nanogels in the thermosensitive gel achieved sustained and controlled release of BDNF with non-Fick's diffusion, exhibited rapid brain distribution, and achieved nearly 50-fold enhanced bioavailability compared to oral quercetin. Quercetin nanogels as a therapeutic drug delivery carrier exerted antidepressant effects on reserpine-induced rats, effectively delivered BDNF to reverse despair behavior in stress-induced mice, and exhibited antidepressant effects on chronic mild unpredictable stimulation (CUMS) rats. These antidepressant effects of BDNF-Quercetin nanogels for CUMS rats are associated with the regulation of the glutamatergic system, PI3K-Akt, and BDNF-TrkB signaling pathway. CONCLUSIONS: In this study, we provide a promising strategy for brain delivery of BDNF for treating depressive disorders, effectively achieved through combining quercetin nanogels and intranasal administration.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Quercetina , Ratas , Ratones , Animales , Quercetina/farmacología , Quercetina/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/tratamiento farmacológico , Depresión/metabolismo , Nanogeles , Alginatos , Fosfatidilinositol 3-Quinasas/metabolismo , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/metabolismo , Hipocampo , Modelos Animales de Enfermedad
3.
Biomacromolecules ; 22(8): 3510-3521, 2021 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-34288655

RESUMEN

Hydrophobic acrylic intraocular lenses (IOLs) are widely used in cataract treatment for posterior capsule opacification (PCO) prophylaxis. However, undesired glistening and postoperative endophthalmitis are two major potential risks. Hence, a series of poly(2-phenoxyethyl methacrylate-co-2-phenoxyethyl acrylate-co-2-ethylhexyl methacrylate) (PPPE) acrylic IOL materials were synthesized for "glistening-free" optimization. The selected PPPE with 2% 2-ethylhexyl methacrylate showed excellent optical, foldable, and thermomechanical properties. The anterior surface of PPPE was coated with polydopamine followed by gentamycin conjugation (PDA/GS). It inhibited bacterial adhesion by 74% and decreased the biofilm thickness by 87%. In inflammatory mimicking conditions, bacterial proliferation was restrained, with acidic-dependent GS release behavior. The surface of PPPE toward the posterior capsule remained hydrophobic. It was conducive to human lens epithelial cell adhesion, collagen IV and fibronectin adsorption, and the following "sealed sandwich structure" formation. In summary, the PPPE with a dual-side heterogeneous surface displayed good application prospects in postoperative endophthalmitis and PCO prevention.


Asunto(s)
Opacificación Capsular , Endoftalmitis , Cápsula del Cristalino , Lentes Intraoculares , Materiales Biocompatibles , Endoftalmitis/prevención & control , Humanos , Complicaciones Posoperatorias/prevención & control , Diseño de Prótesis
4.
Molecules ; 26(5)2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33668746

RESUMEN

Cancer immunotherapies have generated some miracles in the clinic by orchestrating our immune system to combat cancer cells. However, the safety and efficacy concerns of the systemic delivery of these immunostimulatory agents has limited their application. Nanomedicine-based delivery strategies (e.g., liposomes, polymeric nanoparticles, silico, etc.) play an essential role in improving cancer immunotherapies, either by enhancing the anti-tumor immune response, or reducing their systemic adverse effects. The versatility of working with biocompatible polymers helps these polymeric nanoparticles stand out as a key carrier to improve bioavailability and achieve specific delivery at the site of action. This review provides a summary of the latest advancements in the use of polymeric micelles for cancer immunotherapy, including their application in delivering immunological checkpoint inhibitors, immunostimulatory molecules, engineered T cells, and cancer vaccines.


Asunto(s)
Inmunoterapia , Neoplasias/terapia , Polímeros/química , Animales , Sistemas de Liberación de Medicamentos , Humanos , Micelas , Nanomedicina , Nanopartículas/química , Neoplasias/inmunología
5.
Pharm Res ; 35(10): 196, 2018 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-30143878

RESUMEN

PURPOSE: The aim of this study was to design hyaluronic acid (HA) layer-by-layer (LbL) nanoparticles, which carried paclitaxel (PTX) and Indocyanine green (ICG) to both tumor cells and tumor associated cells to achieve synergistic chemo-photothermal therapeutic effect. METHODS: The LbL-engineered nanoparticles (PDIH) were prepared by dopamine self-polymerization on PTX nanocrystal to form thin, surface-adherent polydopamine (PDA) films, which subsequently absorbed ICG and HA. The tumor cell and tumor associated cell targeting and antitumor efficacy of PDIH were investigated both in vitro an in vivo using 4 T1 murine mammary cancer cell lines and mice bearing orthotopic 4 T1 breast tumor. RESULTS: PDIH presented a long-rod shape in TEM and showed enhanced photothermal effect and cytotoxicity upon NIR laser irradiation both in vitro and in vivo. PDIH also displayed high target ability to CD44 overexpressed tumor cells and tumor associated cells mediated by HA. In vivo antitumor study indicated that PDIH therapeutic strategy could achieve remarkable antitumor efficacy. CONCLUSION: PDIH showed excellent tumor-targeting property and chemo-photothermal therapeutic efficacy.


Asunto(s)
Antineoplásicos/química , Portadores de Fármacos/química , Ácido Hialurónico/química , Nanopartículas/química , Fototerapia/métodos , Animales , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Terapia Combinada , Liberación de Fármacos , Femenino , Verde de Indocianina/administración & dosificación , Verde de Indocianina/química , Indoles/química , Neoplasias Mamarias Experimentales/terapia , Ratones , Paclitaxel/administración & dosificación , Paclitaxel/química , Tamaño de la Partícula , Polimerizacion , Polímeros/química
6.
Drug Dev Ind Pharm ; 44(12): 2005-2012, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30058387

RESUMEN

It is necessary to discover a novel antitumor liposome with prolonged circulation time, high efficacy, and low cost. Here, we reported a liposomal honokiol (HNK) prepared with a new type of excipient, Kolliphor HS15, which was termed as HS15-LP-HNK. In addition, we employed PEGylated liposomal honokiol (PEG-LP-HNK) as positive control. The HS15-LP-HNK was prepared by thin-film hydration method. It was near-spherical morphology with an average size of 80.62 ± 0.72 nm (PDI = 0.234 ± 0.007) and a mean zeta potential of -3.91 ± 0.06 mv. In vivo studies exhibited no significant difference between HS15-LP-HNK and PEG-LP-HNK. The pharmacokinetic and biodistribution results showed that HS15-LP-HNK could improve the bioavailability and increase tumor accumulation of honokiol. Furthermore, HS15-LP-HNK could enhance antitumor efficacy of honokiol with low toxicity. In summary, HS15-LP-HNK is promising in tumor targeted drug delivery system.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Compuestos de Bifenilo/farmacología , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Excipientes/química , Lignanos/farmacología , Animales , Antineoplásicos Fitogénicos/química , Disponibilidad Biológica , Compuestos de Bifenilo/química , Compuestos de Bifenilo/uso terapéutico , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Línea Celular Tumoral/trasplante , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Lignanos/química , Lignanos/uso terapéutico , Liposomas , Magnolia/química , Ratones , Ratones Endogámicos C57BL , Polietilenglicoles/química , Ratas , Ratas Wistar , Estearatos/química , Distribución Tisular
7.
Dent Mater ; 40(10): 1669-1676, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39095247

RESUMEN

The clinical failure mode of dental crown ceramics involves radial cracking at the interface, driven by the surface tension generated from the flexure of the ceramic layer on the subsurface. This results in a reduced lifespan for most all-ceramic dental crowns. Therefore, investigating optimal material combinations to reduce stress concentration in dental crown materials has become crucial for future successful clinical applications. The anisotropic complex structures of natural materials, such as nacre, could potentially create suitable strong and damage-resistant materials. Their imitation of natural structural optimisation and mechanical functionality at both the macro- and micro-levels minimises weaknesses in dental crowns. This research aims to optimise cost-effective, freeze-casted bioinspired composites for the manufacture of novel, strong, and tough ceramic-based dental crowns. To this end, multilayer alumina (Al2O3) composites with four different polymer phases were tested to evaluate their bending behaviour and determine their flexural strength. A computational model was developed and validated against the experimental results. This model includes Al2O3 layers that undergo gentle compression and distribute stress, while the polymer layers act as stress relievers, undergoing plastic deformation to reduce stress concentration. Based on the experimental data and numerical modelling, it was concluded that these composites exhibit variability in mechanical properties, primarily due to differences in microstructures and their flexural strength. Furthermore, the findings suggest that bioinspired Al2O3-based composites demonstrate promising deformation and strengthening behaviour, indicating potential for application in the dental field.


Asunto(s)
Óxido de Aluminio , Resinas Compuestas , Resistencia Flexional , Ensayo de Materiales , Óxido de Aluminio/química , Resinas Compuestas/química , Coronas , Materiales Dentales/química , Análisis del Estrés Dental , Poliuretanos/química , Cerámica/química , Metacrilatos/química , Polietilenglicoles/química , Propiedades de Superficie , Ácidos Polimetacrílicos/química , Análisis de Elementos Finitos , Estrés Mecánico
8.
Int J Biol Macromol ; 277(Pt 4): 134409, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39097042

RESUMEN

Alginate is a linear polysaccharide with a modifiable structure and abundant functional groups, offers immense potential for tailoring diverse alginate-based materials to meet the demands of biomedical applications. Given the advancements in modification techniques, it is significant to analyze and summarize the modification of alginate by physical, chemical and biological methods. These approaches provide plentiful information on the preparation, characterization and application of alginate-based materials. Physical modification generally involves blending and physical crosslinking, while chemical modification relies on chemical reactions, mainly including acylation, sulfation, phosphorylation, carbodiimide coupling, nucleophilic substitution, graft copolymerization, terminal modification, and degradation. Chemical modified alginate contains chemically crosslinked alginate, grafted alginate and oligo-alginate. Biological modification associated with various enzymes to realize the hydrolysis or grafting. These diverse modifications hold great promise in fully harnessing the potential of alginate for its burgeoning biomedical applications in the future. In summary, this review provides a comprehensive discussion and summary of different modification methods applied to improve the properties of alginate while expanding its biomedical potentials.


Asunto(s)
Alginatos , Materiales Biocompatibles , Alginatos/química , Materiales Biocompatibles/química , Humanos , Animales , Hidrólisis
9.
Colloids Surf B Biointerfaces ; 216: 112560, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35636322

RESUMEN

A simple and versatile strategy for controlled production of monodisperse ethyl cellulose (EC) microcapsules by a single-stage emulsification method has been developed. Monodisperse oil-in-water emulsions, obtained by a microfluidic device, are used as templates for preparing EC microcapsules. Oil-soluble ethyl acetate (EA) is miscible with water, so the interfacial mass transfer between EA and water occurs sufficiently, which leads to water molecules pass through the phase interface and diffuse into emulsion interior. Water molecules aggregate at the interface, and some merge into a large water drop in the central position of the emulsion. After evaporation of EA solvent, monodisperse EC microcapsules create large numbers of pits on the surface with a hollow structure. Curcumin is used as a model drug and embedded in the hollow structure. EC microcapsules have good, sustained drug release efficacy in a simulated intestinal environment, and the release process of EC microcapsules containing 6.14% drug-loaded capacity is fully consistent with the vitro drug release model. Such simple techniques for making EC microcapsules may open a window to the controlled preparation of other multifunctional microcapsules. Besides, it offers theoretical guidance for the study of EC microcapsules as drug carriers and expanding clinical application of curcumin.


Asunto(s)
Curcumina , Cápsulas/química , Celulosa/análogos & derivados , Preparaciones de Acción Retardada , Emulsiones/química , Tamaño de la Partícula , Agua/química
10.
Int J Pharm ; 628: 122277, 2022 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-36241032

RESUMEN

Co-localization of antigens and immunomodulators in the same antigen-presenting cells (APCs) can powerfully activate APCs and enhance immune responses. In this study, the immunomodulator resveratrol (Res) was encapsulated into quaternized chitosan (QCS) - coated liposomes for developing a new nanoparticle delivery system (QCS-Res-LP), and ovalbumin (OVA) was selected as a model antigen and adsorbed on the surface of QCS-Res-LP. The results showed that the particle size of QCS-Res-LP was 96.3 ± 3.52 nm; the PDI value was 0.280 ± 0.010; the Zeta potential was 9.59 ± 0.36 mV. QCS-Res-LP could encapsulate 76.22 ± 1.02 % resveratrol and adsorb 88.2 ± 16.3 % antigen. QCS-Res-LP effectively promoted the co-uptake of antigen and Res by dendritic cells (DCs) with 50-fold greater than resveratrol liposomes (Res-LP). QCS-Res-LP promoted expression levels of CD80, CD86, IL-2, and IL-12 in DCs. QCS-Res-LP did not cause hemolysis. The levels of ovalbumin-specific IgG antibodies and cytokines were significantly increased in mice vaccinated with ovalbumin-absorbed QCS-Res-LP, which induced a mixed Th1/Th2 immune response. In conclusion, these results demonstrated that QCS-coated liposomes enable the co-delivery of antigens and immunomodulators to induce strong and durable immune responses.


Asunto(s)
Quitosano , Liposomas , Animales , Ratones , Liposomas/metabolismo , Quitosano/metabolismo , Resveratrol , Ovalbúmina , Antígenos , Adyuvantes Inmunológicos , Inmunidad , Células Dendríticas
11.
J Biomed Mater Res B Appl Biomater ; 109(10): 1525-1533, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33590658

RESUMEN

The cell microenvironment such as substrate topology plays an important role in biological processes. In this study, microgrooves were successfully produced on surfaces of both thermoplastic and thermoset polymers using cost-effective techniques for mass production. The micropatterning of thermoplastic polystyrene (PS) petri dish was accomplished efficiently using an in-house developed low-cost hot embossing system. The high replication fidelity of the microgroove with depth and width of 2 µm and spacing of 2 µm was achieved by using silicone rubber as a soft counter mold. This patterned petri dish subsequently served as the cast to replicate the micropattern onto thermoset polydimethylsiloxane (PDMS). It was found that the micropattern increased the hydrophobicity of both PS and PDMS surfaces. The effect of the substrate micropattern on cellular behaviors was preliminarily investigated with untreated and treated PS petri dish as well as PDMS. The results show that the micropattern significantly improved cell adhesion and proliferation for cells cultured on untreated PS petri dish and PDMS substrates. Moreover, the micropattern induced obvious cell alignment along the microgrooves for culturing on all substrates which were studied.


Asunto(s)
Materiales Biocompatibles Revestidos/química , Dimetilpolisiloxanos/química , Poliestirenos/química , Adhesión Celular , Técnicas de Cultivo de Célula , Proliferación Celular , Materiales Biocompatibles Revestidos/metabolismo , Dimetilpolisiloxanos/metabolismo , Interacciones Hidrofóbicas e Hidrofílicas , Células Madre Mesenquimatosas , Propiedades de Superficie
12.
Nanoscale ; 12(5): 3359-3369, 2020 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-31984408

RESUMEN

The tumor microenvironment (TME) acts as an ecosystem that includes not only tumor cells, but also stromal cells such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). In addition, the abnormal extracellular environment (ECM), of which the mechanical forces are regulated by fibronectin (Fn) and collagen I, orchestrates tumorigenesis and progression by directly promoting invasion and cellular transformation of the ecosystem. Herein, we develop a novel peptide-modified liposome incorporated into doxorubicin (FnBPA5-AAN-Dox) as an ecological therapy system, which targets not only the cellular compartment but also non-cellular components of breast cancer. FnBPA5 is a Fn-binding peptide showing high affinity with relaxed Fn and collagen I in the ECM as well as α-SMA-expressing CAFs. However, the fast clearance by Fn-excreting organs such as the liver and spleen limits the accumulation of FnBPA5-Dox in the TME. The AAN peptide, which targets legumain overexpressed in the TAMs, could extend the circulation time and improve the therapeutic response as well as modulate the tumor immune microenvironment (TMIE). Given twice at an equivalent dose of 5 mg kg-1 intravenously, the multi-in-one 'ecological therapy' applied AAN-FnBPA5-Dox showed excellent antitumor efficacy in 4T1 breast cancer mice, and the tumor growth inhibition (TGI) is up to 98.20% compared with saline. Immunofluorescence, flow cytometry and reverse transcription polymerase chain reaction (RT-PCR) results revealed that the dramatic improvement in antitumor efficacy can be attributed to the multifunctional targets of the drug delivery system.


Asunto(s)
Doxorrubicina/análogos & derivados , Sistemas de Liberación de Medicamentos , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Péptidos , Microambiente Tumoral/efectos de los fármacos , Células 3T3 , Animales , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacología , Femenino , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos BALB C , Péptidos/química , Péptidos/farmacocinética , Péptidos/farmacología , Polietilenglicoles/química , Polietilenglicoles/farmacocinética , Polietilenglicoles/farmacología , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley
13.
Pharm Nanotechnol ; 8(5): 391-398, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32787769

RESUMEN

BACKGROUND: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDA-approved PEG-liposomes of DOX for the treatment of over 600,000 cancer patients, and it can overcome doxorubicin-induced cardiomyopathy and other side effects and prolong life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment. OBJECTIVE: We intended to prepare a novel DOX liposome that was prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical application. METHODS: DOX liposomes were prepared using the combination of thin-film dispersion ultrasonic method and ammonium sulfate gradient method and the factors that influenced formulation quality were optimized. After formulation, particle size, entrapment efficiency, drug loading, stability, and pharmacokinetics were determined. RESULTS: DOX liposomes were near-spherical morphology with the average size of 90 nm and polydispersity index (PDI) of less than 0.30. The drug loading was up to 7.5%, and the entrapment efficiency was over 80%. The pharmacokinetic studies showed that free DOX could be easily removed and the blood concentration of free DOX group was significantly lower than that of DOX liposomes, which indicated that the novel DOX liposome had a certain sustainedrelease effect. CONCLUSION: In summary, DOX liposome is economical and easy-prepared with prolonged circulation time. Lay Summary: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDAapproved PEG-liposomes of DOX to treat over 600.000 cancer patients, overcoming doxorubicin- induced cardiomyopathy and other side effects and prolonging life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment. We intend to prepare a novel DOX liposome prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical use. The novel DOX liposome is economical and easy-prepared with prolonged circulation time.


Asunto(s)
Antibióticos Antineoplásicos/farmacocinética , Doxorrubicina/análogos & derivados , Lecitinas/química , Polietilenglicoles/química , Estearatos/química , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/sangre , Antibióticos Antineoplásicos/química , Preparaciones de Acción Retardada , Doxorrubicina/administración & dosificación , Doxorrubicina/sangre , Doxorrubicina/química , Doxorrubicina/farmacocinética , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Inyecciones Intravenosas , Liposomas , Masculino , Tamaño de la Partícula , Polietilenglicoles/administración & dosificación , Polietilenglicoles/farmacocinética , Ratas Sprague-Dawley , Tecnología Farmacéutica
14.
Biomaterials ; 249: 120055, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32315863

RESUMEN

The ubiquitous interactions between tumor cells and the surrounding microenvironment contribute to tumor metastasis, interrupting these communications has, therefore, a great potential for antimetastasis therapy. Here, we describe an in situ self-assembly strategy that limits direct contact between tumor cells and the tumor microenvironment (TME). In this strategy, the Lys-Leu-Val-Phe-Phe (KLVFF) peptide motifs are targeted to the tumor by hyaluronic acid (HA) functionalized liposomes and spontaneously undergo self-assembly to form nanofibers with a net-like structure wrapping around tumor cells. The fibrous nanostructures bury the membrane protrusions and thus hinder the migration and invasion of tumor cells, especially the transmigration through the fenestrated endothelium. The nanofibril coatings on tumor cells significantly block tumor cells induced platelet aggregation in vitro and prevent the adhesion of platelet around circulating tumor cells (CTCs) in vivo, thus limit the pro-metastasis effect of platelets and prevent the early metastasis. Furthermore, the nano-nets stably retain in the primary tumor site for over 72 h and effectively prevent the activation of intratumoral platelet, which suppress tumor progression and the spontaneous lung metastasis in 4T1 breast cancer mice model. Our study paves a promising avenue to combat tumor metastasis by regulating the interactions between tumor cells and the TME.


Asunto(s)
Neoplasias de la Mama , Células Neoplásicas Circulantes , Animales , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Humanos , Liposomas , Ratones , Metástasis de la Neoplasia , Células Neoplásicas Circulantes/patología , Péptidos , Microambiente Tumoral
15.
PDA J Pharm Sci Technol ; 73(6): 572-587, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31101708

RESUMEN

Container closure integrity (CCI) is one of the requirements for a sterile packaging system. For vial-based systems, the capping process is a critical step in creating and ensuring an adequate seal with acceptable CCI. Container closure integrity tests (CCITs) such as the dye ingress and the helium leak rate are two methods among many that, in the appropriate scenario, help to challenge this required attribute. The use of locked-in stopper compression (compression under the crimp seal post capping) enables correlation of these methods to CCI and seal quality. In fact, the overall acceptability of a seal can be evaluated using quantitative and qualitative methods. Usually lost in these assessments is the existence of seal cosmetics as an essential additional seal quality attribute. Unacceptable cosmetic quality can have a major impact on manufacturing (reduced batch output, high yield cost, etc.) and user (perceived low quality, brand image, potential injury, etc.) experiences. Interestingly, the aesthetics of a seal is also impacted by the capping process which is quite complicated because the acceptance criteria for aesthetics of a seal is subjective. Ultimately, this affects commercial manufacturing efficiency and CCI. Here, we present a simple methodology for package selection and evaluated multiple package configurations using locked-in stopper compression (through residual seal force, RSF) measurements and seal aesthetics analyses (using a semi-quantitative aesthetics scale). The integrity of the seals was analyzed using multiple CCIT methods. We determined that component dimensions such as the seal length play a major role in obtaining proper seal aesthetics and integrity. This can ultimately enable the selection of robust packaging components that provide an adequate range of manufacturing conditions without cosmetic defects. A failure to do this could result in high rejects during drug product visual inspection culminating in low batch yield, high costs or could pose harm to patients if suitable CCI is not achieved.LAY ABSTRACT: One common container closure system for parenteral drug products includes a glass vial, rubber stopper, and aluminum crimp seal. The capping process, in which the elastomeric closure is compressed against the vial by means of an aluminum crimp seal, is key to ensuring an optimal seal from both an aesthetic and CCI perspective. Ensuring a robust capping process must include a deep and necessary understanding of the interconnection between the selected components, desired aesthetics of the seal, stopper compression, residual seal force, and CCI; the way in which the capper is configured (sealing parameters) will play a part in addition to the "style" used in manufacturing. Previous published studies have focused on capping process controls to only ensure CCI. Here, we present a useful methodology for selecting appropriate components and capping process parameters using a scaled-down approach to achieve elegant seal quality and CCI simultaneously. Dimensional analysis and capping design of experiments (DOEs) were conducted on lab-scale equipment that was representative of commercial configurations. The seals made from these studies were analyzed using residual seal force, helium leak, and dye ingress methods. The results and their implications were discussed with regard to the operating principle of the rail-type capping machine.


Asunto(s)
Contaminación de Medicamentos/prevención & control , Embalaje de Medicamentos/normas , Esterilización , Tecnología Farmacéutica/métodos , Aluminio/química , Industria Farmacéutica , Vidrio , Ensayo de Materiales , Control de Calidad , Goma/química
16.
ACS Appl Mater Interfaces ; 11(45): 42534-42548, 2019 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-31479235

RESUMEN

Biomimetic design has been extensively investigated. The only FDA-approved biomimetic albumin-bound paclitaxel may not be beneficial to some treated patients due to rapid dissociation upon intravenous infusion and no substantial improvement in the drug's pharmacokinetics or biodistribution. Herein, we developed an alternative and injectable preformed albumin-bound anticancer drug delivery. We combined HSA, Kolliphor HS 15 (HS15), and pirarubicin (THP) via purely physical forces in a thin-film hydration method to obtain an albumin-bound complex of HSA-THP. The lack of any chemical reactions preserves HSA bioactivity, in contrast to the destroyed secondary structure within AN-THP (albumin nanoparticle of THP) for the harsh manipulation during preparation. In vitro, HSA-THP showed a significantly higher cellular uptake efficiency than THP, and the complex was more cytotoxic. In vivo, HSA-THP showed longer half-life than THP. It also exhibited greater tumor accumulation and tumor penetration via gp60- and SPARC-mediated biomimetic transport than THP and AN-THP. As a result, HSA-THP showed strong antitumor and antimetastasis efficacy, with relatively little toxicity. These results suggest the clinical potential of biomimetic tumor-targeted drug delivery.


Asunto(s)
Albúminas/química , Antineoplásicos/administración & dosificación , Doxorrubicina/análogos & derivados , Sistemas de Liberación de Medicamentos/métodos , Neoplasias/tratamiento farmacológico , Polietilenglicoles/química , Estearatos/química , Animales , Antineoplásicos/química , Línea Celular Tumoral , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/instrumentación , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Metástasis de la Neoplasia/prevención & control , Neoplasias/patología , Ratas , Ratas Sprague-Dawley
17.
Drug Deliv ; 25(1): 388-397, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29378465

RESUMEN

Glioma, one of the most common brain tumors, remains a challenge worldwide. Due to the specific biological barriers such as blood-brain barrier (BBB), cancer stem cells (CSCs), tumor associated macrophages (TAMs), and vasculogenic mimicry channels (VMs), a novel versatile targeting delivery for anti-glioma is in urgent need. Here, we designed a hyaluronic acid (HA) ion-pairing nanoparticle. Then, these nanoparticles were encapsulated in liposomes, termed as DOX-HA-LPs, which showed near-spherical morphology with an average size of 155.8 nm and uniform distribution (PDI = 0.155). HA was proven to specifically bind to CD44 receptor, which is over-expressed on the surface of tumor cells, other associated cells (such as CSCs and TAMs) and VMs. We systematically investigated anti-glioma efficacy and mechanisms in vivo and in vitro. The strong anti-glioma efficacy could attribute to the accumulation in glioma site and the regulation of tumor microenvironment with depletion of TAMs, inhibition of VMs, and elimination of CSCs.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Ácido Hialurónico/administración & dosificación , Nanopartículas/administración & dosificación , Microambiente Tumoral/efectos de los fármacos , Animales , Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Ácido Hialurónico/metabolismo , Liposomas , Masculino , Ratones , Ratones Endogámicos BALB C , Nanopartículas/metabolismo , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , Resultado del Tratamiento , Microambiente Tumoral/fisiología
18.
J Control Release ; 271: 21-30, 2018 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-29277681

RESUMEN

The chemotherapy of aggressive breast tumor is usually accompanied by a poor prognosis because of the metastasis of tumor cells. Thus, it is important to simultaneously enhance antitumor and anti-metastasis efficacy. Fibronectin and its complexes are expressed on the walls of tumor vessels and in tumor stroma. Moreover, the expression of fibronectin in metastatic sites is even higher than that in primary tumors. Herein, we designed a fibronectin-targeting CREKA-modified liposomal doxorubicin (CREKA-Lipo-Dox) for the therapy of metastatic breast tumor. CREKA-Lipo was uniformly formed with high entrapment efficiency. It exhibited longer blood circulation time compared with free Dox, and there was no significant change compared with PEG-Lipo-Dox. Immunofluorescence results revealed that the CREKA-Lipo-Dox could specifically bind to fibronectin in the tumor vessels and tumor stroma. The antitumor and anti-metastasis efficacy of CREKA-loaded liposome was more obvious than that of free Dox or unmodified Dox-Lipo. Taken together, binding fibronectin by CREKA could be an attractive therapeutic strategy for metastatic breast cancer in the future.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/análogos & derivados , Fibronectinas/metabolismo , Oligopéptidos/administración & dosificación , Animales , Antibióticos Antineoplásicos/farmacocinética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Femenino , Masculino , Ratones Endogámicos BALB C , Oligopéptidos/farmacocinética , Polietilenglicoles/administración & dosificación , Polietilenglicoles/farmacocinética , Ratas Sprague-Dawley
19.
Artículo en Inglés | MEDLINE | ID: mdl-29483932

RESUMEN

Resveratrol, a polyphenolic plant antitoxin, has a wide range of pharmacological activities. In this study, we systematically evaluated the effects of resveratrol dry suspension (RDS) on immune function in piglets that were treated with different doses of RDS for 2 weeks. The results showed that the RDS has significant effects on the development, maturation, proliferation, and transformation of T lymphocytes. RDS could regulate humoral immune responses by upregulating the release of IFN-γ and downregulating the release of TNF-α. After piglets were vaccinated against classical swine fever virus and foot-and-mouth disease virus, the antibody titers were significantly increased. RDS treatment showed an excellent resistance to enhance T-SOD activity. Values of blood routine and blood biochemistry showed no toxicity. These results suggested that RDS could be considered as an adjuvant to enhance immune responses to vaccines, as well as dietary additives for animals to enhance humoral and cellular immunity.

20.
Hepatobiliary Pancreat Dis Int ; 4(4): 582-4, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16286267

RESUMEN

BACKGROUND: The configuration and course of liver blood vessels (LBVs) are involved in the study of pathogenesis of hepatic diseases including liver cirrhosis, tissue engineering of the liver and surgical treatment of diseases of the liver and gallbladder. In the study of vascularization in tissue engineering of the liver in particular, the work we should do is to get the anatomy data of LBVs for computer-aided reconstruction of digital model of LBVs. In doing so, the casting sample of rat liver blood vessels (RLBVs) is fabricated and the data of each section of the sample is harvested. METHODS: Liquid polymer preparation (8%-10%), which was made of chlorinated poly vinyl chloride (CPVC) as a solute, acetone as solvent and pigment, was injected into the RLBVs of 40 rats. Once acetone evaporated, the preparation solidified. When the cells and connective tissue were dissolved by hydrochloric acid, a casting sample of RLBV was left. The sample was embedded in paraffin and cut into sections. The data of each section of RLBVs was collected by digital camera. RESULTS: In 36 rats, the casting sample of RLBVs was made successfully by this method. The diameter of the hepatic arteries varied from 0.8 to 0.2 mm, the portal veins from 2.0 to 0.1 mm, and the hepatic veins from 2.2 to 0.2 mm. In each rat, about 150 photographs of the sections of RLBVs were taken. CONCLUSION: The method described above is feasible for getting experimental data for computer-aided reconstruction of the digital model of RLBVs.


Asunto(s)
Circulación Hepática , Acetona , Animales , Diseño Asistido por Computadora , Procesamiento de Imagen Asistido por Computador/métodos , Cloruro de Polivinilo , Ratas , Ratas Sprague-Dawley
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA