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1.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732136

RESUMEN

In the context of sustainable agriculture and biomaterial development, understanding and enhancing plant secondary cell wall formation are crucial for improving crop fiber quality and biomass conversion efficiency. This is especially critical for economically important crops like upland cotton (Gossypium hirsutum L.), for which fiber quality and its processing properties are essential. Through comprehensive genome-wide screening and analysis of expression patterns, we identified a particularly high expression of an R2R3 MYB transcription factor, GhMYB52 Like, in the development of the secondary cell wall in cotton fiber cells. Utilizing gene-editing technology to generate a loss-of-function mutant to clarify the role of GhMYB52 Like, we revealed that GhMYB52 Like does not directly contribute to cellulose synthesis in cotton fibers but instead represses a subset of lignin biosynthesis genes, establishing it as a lignin biosynthesis inhibitor. Concurrently, a substantial decrease in the lint index, a critical measure of cotton yield, was noted in parallel with an elevation in lignin levels. This study not only deepens our understanding of the molecular mechanisms underlying cotton fiber development but also offers new perspectives for the molecular improvement of other economically important crops and the enhancement of biomass energy utilization.


Asunto(s)
Fibra de Algodón , Regulación de la Expresión Génica de las Plantas , Gossypium , Lignina , Proteínas de Plantas , Lignina/biosíntesis , Gossypium/genética , Gossypium/metabolismo , Gossypium/crecimiento & desarrollo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Pared Celular/metabolismo , Pared Celular/genética , Celulosa/biosíntesis , Celulosa/metabolismo , Vías Biosintéticas
2.
BMC Anesthesiol ; 20(1): 127, 2020 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-32460699

RESUMEN

BACKGROUND: Postoperative pulmonary complications (PPCs) are common and significant problems for oral and maxillofacial surgery patients. Dexmedetomidine (DEX), an α2-adrenoreceptor agonist, has been proven having lung protection effects. However, since now, there has not been final conclusion about whether DEX can reduce the incidence of PPCs. We hypothesize that, in oral and maxillofacial surgery with fibular free flap reconstruction patients, DEX may decrease the incidence of PPCs. METHODS: This was a prospective, double-blind, randomized, placebo-controlled, single-centered trial with two parallel arms. A total of 160 patients at intermediate-to-high risk of PPCs undergoing oral and maxillofacial surgery with fibular free flap reconstruction and tracheotomy were enrolled and randomized to receive continuous infusion of either DEX or placebo (normal saline). 0.4 µg/kg of DEX was given over 10mins as an initial dose followed by a maintaining dose of 0.4 µg/kg/h till the second day morning after surgery. At the same time, the normal saline was administered a similar quantity. The primary outcome was the incidence of PPCs according to Clavien-Dindo score within 7 days after surgery. RESULTS: The two groups had similar characteristics at baseline. 18(22.5%) of 80 patients administered DEX, and 32(40.0%) of 80 patient administered placebo experienced PPCs within the first 7 days after surgery (relative risk [RR] 0.563,95% confidence interval [CI] 0.346-0.916; P = 0.017). In the first 7 days after surgery, the DEX group had a lower incidence of PPCs and a better postoperative survival probability (Log-rank test, P = 0.019), and was less prone to occur PPCs (Cox regression, P = 0.025, HR = 0.516). When the total dose of DEX was more than 328 µg, the patients were unlikely to have PPCs (ROC curve, AUC = 0.614, P = 0.009). CONCLUSIONS: For patients undergoing oral and maxillofacial surgery with fibular free flap reconstruction and tracheotomy who were at intermediate or high risk of developing PPCs, continuous infusion of DEX could decrease the occurrence of PPCs during the first 7 days after surgery and shorten the length of hospital stay after surgery, but did not increase the prevalence of bradycardia or hypotension. TRIAL REGISTRATION: Chinese Clinical Trial Registry, www.chictr.org.cn, number: ChiCTR1800016153; Registered on May 15, 2018.


Asunto(s)
Dexmedetomidina/uso terapéutico , Colgajos Tisulares Libres , Enfermedades Pulmonares/prevención & control , Procedimientos Quirúrgicos Orales/efectos adversos , Procedimientos de Cirugía Plástica/efectos adversos , Complicaciones Posoperatorias/prevención & control , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
3.
Mol Pharm ; 13(9): 3069-79, 2016 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-27417390

RESUMEN

As the hearts of tumor cells, the nucleus is the ultimate target of many chemotherapeutic agents and genes. However, nuclear drug delivery is always hampered by multiple intracellular obstacles, such as low efficiency of lysosome escape and insufficient nuclear trafficking. Herein, an N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-based drug delivery system was designed, which could achieve direct cytoplasmic delivery by a nonendocytic pathway and transport into the nucleus in a microtubules dependent fashion. A special targeting peptide (MT), derived from an endogenic parathyroid hormone-related protein, was conjugated to the polymer backbone, which could accumulate into the nucleus a by microtubule-mediated pathway. The in vitro studies found that low temperature and NaN3 could not influence the cell internalization of the conjugates. Besides, no obvious overlay of the conjugates with lysosome demonstrated that the polymer conjugates could enter the tumor cell cytoplasm by a nonendocytic pathway, thus avoiding the drug degradation in the lysosome. Furthermore, after suppression of the microtubule dynamics with microtubule stabilizing docetaxel (DTX) and destabilizing nocodazole (Noc), the nuclear accumulation of polymeric conjugates was significantly inhibited. Living cells fluorescence recovery after photobleaching study found that the nuclear import rate of conjugates was 2-fold faster compared with the DTX and Noc treated groups. These results demonstrated that the conjugates transported into the nucleus in a microtubules dependent way. Therefore, in addition to direct cytoplasmic delivery, our peptide conjugated polymeric platform could simultaneously mediate nuclear drug accumulation, which may open a new path for further intracellular genes/peptides delivery.


Asunto(s)
Citoplasma/metabolismo , Metacrilatos/química , Microtúbulos/metabolismo , Polímeros/química , Transporte Activo de Núcleo Celular/fisiología , Apoptosis/fisiología , Recuperación de Fluorescencia tras Fotoblanqueo , Células HeLa , Humanos , Microtúbulos/química
4.
Angew Chem Int Ed Engl ; 55(10): 3309-12, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26846161

RESUMEN

Effective delivery of therapeutic proteins is a formidable challenge. Herein, using a unique polymer family with a wide-ranging set of cationic and hydrophobic features, we developed a novel nanoparticle (NP) platform capable of installing protein ligands on the particle surface and simultaneously carrying therapeutic proteins inside by a self-assembly procedure. The loaded therapeutic proteins (e.g., insulin) within the NPs exhibited sustained and tunable release, while the surface-coated protein ligands (e.g., transferrin) were demonstrated to alter the NP cellular behaviors. In vivo results revealed that the transferrin-coated NPs can effectively be transported across the intestinal epithelium for oral insulin delivery, leading to a notable hypoglycemic response.


Asunto(s)
Nanopartículas/química , Polímeros/química , Proteínas/química , Células CACO-2 , Humanos
5.
Angew Chem Int Ed Engl ; 55(25): 7091-7094, 2016 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-27140428

RESUMEN

RNA interference (RNAi) gene silencing technologies have shown significant potential for treating various diseases, including cancer. However, clinical success in cancer therapy remains elusive, mainly owing to suboptimal in vivo delivery of RNAi therapeutics such as small interference RNA (siRNA) to tumors. Herein, we developed a library of polymers that respond to a narrow pH change (ultra-pH-responsive), and demonstrated the utility of these materials in targeted and deep tumor-penetrating nanoparticle (NP) for in vivo RNAi. The new NP platform is mainly composed of the following key components: i) internalizing RGD (iRGD) to enhance tumor targeting and tissue penetration; ii) polyethylene glycol (PEG) chains to prolong blood circulation; and iii) sharp pH-responsive hydrophobic polymer to improve endosome escape. Through systematic studies of structure-function relationship, the optimized RNAi NPs (<70 nm) showed efficient gene silencing and significant inhibition of tumor growth with negligible toxicities in vivo.


Asunto(s)
Preparaciones de Acción Retardada/química , Técnicas de Transferencia de Gen , Nanopartículas/química , Neoplasias/terapia , ARN Interferente Pequeño/administración & dosificación , Tratamiento con ARN de Interferencia/métodos , Línea Celular Tumoral , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Proteínas Inhibidoras de la Apoptosis/genética , Neoplasias/genética , Oligopéptidos/química , Polietilenglicoles/química , Polímeros/química , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacocinética , ARN Interferente Pequeño/uso terapéutico , Survivin
6.
Nanomedicine ; 10(5): 897-900, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24650883

RESUMEN

The development of controlled-release nanoparticle (NP) technologies has great potential to further improve the therapeutic efficacy of RNA interference (RNAi), by prolonging the release of small interfering RNA (siRNA) for sustained, long-term gene silencing. Herein, we present an NP platform with sustained siRNA-release properties, which can be self-assembled using biodegradable and biocompatible polymers and lipids. The hybrid lipid-polymer NPs showed excellent silencing efficacy, and the temporal release of siRNA from the NPs continued for over one month. When tested on luciferase-expressed HeLa cells and A549 lung carcinoma cells after short-term transfection, the siRNA NPs showed greater sustained silencing activity than lipofectamine 2000-siRNA complexes. More importantly, the NP-mediated sustained silencing of prohibitin 1 (PHB1) generates more effective tumor cell growth inhibition in vitro and in vivo than the lipofectamine complexes. We expect that this sustained-release siRNA NP platform could be of interest in both fundamental biological studies and clinical applications. FROM THE CLINICAL EDITOR: Emerging gene silencing applications could be greatly enhanced by prolonging the release of siRNA for sustained gene silencing. This team of scientists presents a hybrid lipid-polymer nanoparticle platform that successfully accomplishes this goal, paving the way to future research studies and potential clinical applications.


Asunto(s)
Lípidos/química , Nanopartículas/química , Polímeros/química , Línea Celular Tumoral , Silenciador del Gen , Células HeLa , Humanos , Prohibitinas , ARN Interferente Pequeño
7.
J Hazard Mater ; 474: 134573, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38824779

RESUMEN

It has been demonstrated that microplastics (MPs) may be inadvertently ingested by aquatic animals, causing harm to their physiological functions and potentially entering the food chain, thereby posing risks to human food safety. To achieve an environmentally friendly and efficient reduction of MPs in freshwater environments, this experiment investigates the depuration effect of C. demersum on MPs using three common aquatic animals: Macrobrachium nipponense, Corbicula fluminea, and Bellamya aeruginosa as research subjects. The amounts of MPs, digestive enzyme activity, oxidative stress index, and energy metabolism enzyme activity in the digestive and non-digestive systems of three aquatic animals were measured on exposure days 1, 3, and 7 and on depuration days 1 and 3. The results indicated that the depuration effect of C. demersum and the species interaction were significant for the whole individual. Concerning digestive tissue, C. demersum was the most effective in purifying B. aeruginosa. When subjected to short-term exposure to MPs, C. demersum displayed a superior depuration effect. Among non-digestive tissues, C. demersum exhibited the earliest purifying effect on C. fluminea. Additionally, C. demersum alleviated physiological responses caused by MPs. In conclusion, this study underscores C. demersum as a promising new method for removing MPs from aquatic organisms.


Asunto(s)
Corbicula , Microplásticos , Contaminantes Químicos del Agua , Animales , Microplásticos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/metabolismo , Corbicula/metabolismo , Corbicula/efectos de los fármacos , Palaemonidae/metabolismo , Estrés Fisiológico , Estrés Oxidativo/efectos de los fármacos , Chlorophyceae/metabolismo
8.
Int J Biol Macromol ; 260(Pt 1): 129245, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38191109

RESUMEN

Aerogels with low thermal conductivity and high adsorption capacity present a promising solution to curb water pollution caused by organic reagents as well as mitigate heat loss. Although aerogels exhibiting good adsorption capacity and thermal insulation have been reported, materials with mechanical integrity, high flexibility and shear resistance still pose a formidable task. Here, we produced bacterial cellulose-based ultralight multifunctional hybrid aerogels by using freeze-drying followed by chemical vapor deposition silylation method. The hybrid aerogels displayed a low density of 10-15 mg/cm3, high porosity exceeding 99.1 %, low thermal conductivity (27.3-29.2 mW/m.K) and superior hydrophobicity (water contact angle>120o). They also exhibited excellent mechanical properties including superelasticity, high flexibility and shear resistance. The hybrid aerogels demonstrated high heat shielding efficiency when used as an insulating material. As a selective oil absorbent, the hybrid aerogels exhibit a maximum adsorption capacity of up to approximately 156 times its own weight and excellent recoverability. Especially, the aerogel's highly accessible porous microstructure results in an impressive flux rate of up to 162 L/h.g when used as a filter in a continuous oil-water separator to isolate n-hexane-water mixtures. This work presents a novel endeavor to create high-performance, sustainable, reusable, and adaptable multifunctional aerogels.


Asunto(s)
Celulosa , Gases , Adsorción , Liofilización , Calor
9.
Plant Commun ; 5(1): 100681, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-37660253

RESUMEN

Bananas (Musa spp.) are monocotyledonous plants with high genetic diversity in the Musaceae family that are cultivated mainly in tropical and subtropical countries. The fruits are a popular food, and the plants themselves have diverse uses. Four genetic groups (genomes) are thought to have contributed to current banana cultivars: Musa acuminata (A genome), Musa balbisiana (B genome), Musa schizocarpa (S genome), and species of the Australimusa section (T genome). However, the T genome has not been effectively explored. Here, we present the high-quality TT genomes of two representative accessions, Abaca (Musa textilis), with high-quality natural fiber, and Utafun (Musa troglodytarum, Fe'i group), with abundant ß-carotene. Both the Abaca and Utafun assemblies comprise 10 pseudochromosomes, and their total genome sizes are 613 Mb and 619 Mb, respectively. Comparative genome analysis revealed that the larger size of the T genome is likely attributable to rapid expansion and slow removal of transposons. Compared with those of Musa AA or BB accessions or sisal (Agava sisalana), Abaca fibers exhibit superior mechanical properties, mainly because of their thicker cell walls with a higher content of cellulose, lignin, and hemicellulose. Expression of MusaCesA cellulose synthesis genes peaks earlier in Abaca than in AA or BB accessions during plant development, potentially leading to earlier cellulose accumulation during secondary cell wall formation. The Abaca-specific expressed gene MusaMYB26, which is directly regulated by MusaMYB61, may be an important regulator that promotes precocious expression of secondary cell wall MusaCesAs. Furthermore, MusaWRKY2 and MusaNAC68, which appear to be involved in regulating expression of MusaLAC and MusaCAD, may at least partially explain the high accumulation of lignin in Abaca. This work contributes to a better understanding of banana domestication and the diverse genetic resources in the Musaceae family, thus providing resources for Musa genetic improvement.


Asunto(s)
Musa , Musa/genética , Genoma de Planta , Lignina
10.
Polymers (Basel) ; 14(9)2022 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-35566850

RESUMEN

The unpredictable coronavirus pandemic (COVID-19) has led to a sudden and massive demand for face masks, leading to severe plastic pollution. Here, we propose a method for manufacturing biodegradable masks using high-precision 3D printing technology, called "TRespirator", mainly made of banana leaves and dental floss silk fibers. By adding plastic recycling waste appropriately, TRespirator can achieve similar protection and mechanical properties as N95 masks. In addition, microorganisms attracted during the degradation of plant fibers will accelerate the degradation of microplastics. This respirator provides a new idea for solving the global problem of plastic pollution of masks.

11.
Sci Adv ; 8(6): eabj1262, 2022 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-35148178

RESUMEN

Limited circulating tumor cells (CTCs) capturing efficiency and lack of regulation capability on CTC-supportive metastatic niches (MNs) are two main obstacles hampering the clinical translation of conventional liposomes for the treatment of metastatic breast cancers. Traditional delivery strategies, such as ligand modification and immune modulator co-encapsulation for nanocarriers, are inefficient and laborious. Here, a multifunctional Rg3 liposome loading with docetaxel (Rg3-Lp/DTX) was developed, in which Rg3 was proved to intersperse in the phospholipid bilayer and exposed its glycosyl on the liposome surface. Therefore, it exhibited much higher CTC-capturing efficiency via interaction with glucose transporter 1 (Glut1) overexpressed on CTCs. After reaching the lungs with CTCs, Rg3 inhibited the formation of MNs by reversing the immunosuppressive microenvironment. Together, Rg3-Lp/DTX exhibited excellent metastasis inhibition capacity by CTC ("seeds") neutralization and MN ("soil") inhibition. The strategy has great clinical translation prospects for antimetastasis treatment with enhanced therapeutic efficacy and simple preparation process.


Asunto(s)
Ginsenósidos , Células Neoplásicas Circulantes , Línea Celular Tumoral , Ginsenósidos/farmacología , Ginsenósidos/uso terapéutico , Humanos , Liposomas , Microambiente Tumoral
12.
Drug Dev Ind Pharm ; 37(7): 868-74, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21231900

RESUMEN

Particulate systems that could deliver drug specifically to duodenum have not yet been reported. The aim of this study was to develop a novel duodenum-specific drug delivery system based on thiolated chitosan and hydroxypropyl methylcellulose acetate maleate (HPMCAM) for the duodenal ulcer application. Berberine hydrochloride was used as model drug. Thiolated chitosan was synthesized and further used for the preparation of mucoadhesive microspheres. HPMCAM, which is insoluble below pH 3.0 was synthesized and used for the coating of thiolated chitosan microspheres (TCM). The resulting thiolated chitosan immobilized on chitosan was 268.21 ± 18 µmol/g. In vitro mucoadhesion study showed that the mucoadhesion property of TCM was better than that of chitosan microspheres. Morphological observation showed that the HPMCAM coating would maintain its integrity in simulated gastric fluid (SGF) for 2 h and dissolved quickly in simulated pathological duodenal fluid (SPDF; pH 3.3). In vitro drug release studies showed that only 4.75% of the drug was released in SGF for 2 h, while nearly 90% of the drug was released within 6 h after transferring into SPDF.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Duodeno/efectos de los fármacos , Adhesividad , Berberina/administración & dosificación , Quitosano , Úlcera Duodenal/tratamiento farmacológico , Duodeno/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Derivados de la Hipromelosa , Técnicas In Vitro , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Metilcelulosa/análogos & derivados , Microscopía Electrónica de Rastreo , Microesferas , Comprimidos Recubiertos
13.
J Control Release ; 262: 273-283, 2017 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-28774842

RESUMEN

Ligand-functionalization can increase the affinity of nanoparticles (NPs) with targeted cells. However, one major defect of ligands still exists in oral administration: limited receptor recognition. The hindrance of mucus network and deactivation of enzymes severely challenge the targeting efficiency of macromolecular ligands. Inspired by "molecular exchange" between intestinal microbiota and host cells, we anchored microbiota metabolite butyrate on classical "mucus-inert" polyethylene glycol (PEG) NPs. Butyrate has unique advantages of low molecule weight, high hydrophilicity and chemical stability. Interestingly, in vitro mucus-permeability and in vivo mucus distribution of PEG NPs were not impaired by butyrate-functionalization. Enhanced cellular uptake was achieved via specific interaction between butyrate and the monocarboxylate transporter (MCT) on cell membranes, which subsequently ameliorated transepithelial transport and intestinal absorption in the ileum. In vitro safety assessment validated the non-toxicity of butyrate-modification. Finally, insulin-loaded Bu-PEG NPs generated a stronger hypoglycemic response on diabetic rats and 2.87-fold higher oral bioavailability compared with bare PEG NPs. This study demonstrated that butyrate-functionalization could improve the intestinal absorption of macromolecules by overcoming multiple obstacles in the gastrointestinal tract, providing a promising active targeting strategy for oral administration.


Asunto(s)
Butiratos/administración & dosificación , Diabetes Mellitus Experimental/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Nanopartículas/administración & dosificación , Administración Oral , Animales , Butiratos/química , Células CACO-2 , Diabetes Mellitus Experimental/metabolismo , Liberación de Fármacos , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacocinética , Insulina/química , Insulina/farmacocinética , Absorción Intestinal , Masculino , Nanopartículas/química , Polietilenglicoles/administración & dosificación , Polietilenglicoles/química , Ratas Sprague-Dawley
14.
Theranostics ; 7(7): 1990-2002, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28638484

RESUMEN

The present work proposes a unique de-PEGylation strategy for controllable delivery of small interfering RNA (siRNA) using a robust lipid-polymer hybrid nanoparticle (NP) platform. The self-assembled hybrid NPs are composed of a lipid-poly(ethylene glycol) (lipid-PEG) shell and a polymer/cationic lipid solid core, wherein the lipid-PEG molecules can gradually dissociate from NP surface in the presence of serum albumin. The de-PEGylation kinetics of a series of different lipid-PEGs is measured with their respective NPs, and the NP performance is comprehensively investigated in vitro and in vivo. This systematic study reveals that the lipophilic tails of lipid-PEG dictate its dissociation rate from NP surface, determining the uptake by tumor cells and macrophages, pharmacokinetics, biodistribution, and gene silencing efficacy of these hybrid siRNA NPs. Based on our observations, we here propose that lipid-PEGs with long and saturated lipophilic tails might be required for effective siRNA delivery to tumor cells and gene silencing of the lipid-polymer hybrid NPs after systemic administration.


Asunto(s)
Productos Biológicos/farmacocinética , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Polietilenglicoles/metabolismo , ARN Interferente Pequeño/farmacocinética , Adenocarcinoma/tratamiento farmacológico , Animales , Productos Biológicos/administración & dosificación , Productos Biológicos/farmacología , Modelos Animales de Enfermedad , Portadores de Fármacos/administración & dosificación , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células HeLa , Xenoinjertos , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Nanopartículas/administración & dosificación , Polietilenglicoles/administración & dosificación , Células RAW 264.7 , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/farmacología , Resultado del Tratamiento
15.
Drug Deliv ; 23(6): 2015-25, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26203690

RESUMEN

In order to enhance the interaction between nanocarrier and gastrointestinal epithelial cells, we developed nanoparticles (NPs) modified with targeting ligand FQSIYPpIK (FQS), which specifically interact with integrin αvß3 receptor expressing on the intestinal epithelium. The targeting NPs were prepared by coating the insulin-loaded poly(lactide-co-glycolide)-monomethoxy-poly(polyethylene glycol) micelle cores with FQS modified trimethyl chitosan chloride. In in vitro study, the fabricated NPs showed ameliorated drug release profile and improved enzymatic stability compared with micelles alone. In the integrin αvß3 receptor over-expressed Caco-2 cells model, FQS modified NPs exhibited significantly accelerated intracellular uptake due to the active ligand-receptor mediation. Meanwhile, the targeting NPs also showed enhanced transport across the Caco-2 monolayer cells via both transcellular and paracellular pathways. Besides, orally administered FQS modified NPs produced a prominent hypoglycemic response and an increase of the serum insulin concentration in diabetic rats. Both in vitro and in vivo results demonstrated the FQS peptide modified NPs as promising intestinal cell-targeting nanocarriers for efficient oral delivery of insulin.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Insulina/administración & dosificación , Nanopartículas/química , Polietilenglicoles/química , Poliglactina 910/química , Administración Oral , Animales , Células CACO-2 , Quitosano , Humanos , Concentración de Iones de Hidrógeno , Insulina/química , Ligandos , Micelas , Ratas
16.
Theranostics ; 6(4): 470-84, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26941841

RESUMEN

In this study, we reported a simple polydopamine (pD)-based surface modification method to prepare novel nanoparticle-aptamer bioconjugates (Apt-pD-DTX/NPs) for in vivo tumor targeting and enhanced therapeutic effects of breast cancer. With simple preparation procedures, the new functionalized Apt-pD-DTX/NPs could maximumly increase the local effective drug concentration on tumor sites, achieving enhanced treatment effectiveness and minimizing side effects. The dopamine polymerization and aptamer conjugation barely changed the characters of NPs. Both in vitro cell experiments (i.e. endocytosis of fluorescent NPs, in vitro cellular targeting and cytotoxicity assays) and in vivo animal studies (i.e. in vivo imaging, biodistribution and antitumor effects of NPs) demonstrated that the Apt-pD-DTX/NPs could achieve significantly high targeting efficiency and enhanced therapeutic effects compared with clinical Taxotere(®) and NPs without functional modification. Above all, the Apt-pD-DTX/NPs showed great potential as a promising nanoformulation for in vivo breast cancer therapy and the construction of pD-modified NP-aptamer bioconjugates could be of great value in medical use.


Asunto(s)
Antineoplásicos/administración & dosificación , Aptámeros de Nucleótidos/administración & dosificación , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Portadores de Fármacos/administración & dosificación , Indoles/metabolismo , Nanopartículas/administración & dosificación , Polímeros/metabolismo , Animales , Antineoplásicos/farmacología , Aptámeros de Nucleótidos/farmacología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Portadores de Fármacos/química , Humanos , Masculino , Nanopartículas/química , Ratas Sprague-Dawley , Propiedades de Superficie , Resultado del Tratamiento
17.
ACS Nano ; 9(3): 2345-56, 2015 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-25658958

RESUMEN

Nanoparticles (NPs) have demonstrated great potential for the oral delivery of protein drugs that have very limited oral bioavailability. Orally administered NPs could be absorbed by the epithelial tissue only if they successfully permeate through the mucus that covers the epithelium. However, efficient epithelial absorption and mucus permeation require very different surface properties of a nanocarrier. We herein report self-assembled NPs for efficient oral delivery of insulin by facilitating both of these two processes. The NPs possess a nanocomplex core composed of insulin and cell penetrating peptide (CPP), and a dissociable hydrophilic coating of N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA) derivatives. After systematic screening using mucus-secreting epithelial cells, NPs exhibit excellent permeation in mucus due to the "mucus-inert" pHPMA coating, as well as high epithelial absorption mediated by CPP. The investigation of NP behavior shows that the pHPMA molecules gradually dissociate from the NP surface as it permeates through mucus, and the CPP-rich core is revealed in time for subsequent transepithelial transport through the secretory endoplasmic reticulum/Golgi pathway and endocytic recycling pathway. The NPs exhibit 20-fold higher absorption than free insulin on mucus-secreting epithelium cells, and orally administered NPs generate a prominent hypoglycemic response and an increase of the serum insulin concentration in diabetic rats. Our study provides the evidence of using pHPMA as dissociable "mucus-inert" agent to enhance mucus permeation of NPs, and validates a strategy to overcome the multiple absorption barriers using NP platform with dissociable hydrophilic coating and drug-loaded CPP-rich core.


Asunto(s)
Absorción Fisicoquímica , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Insulina/administración & dosificación , Insulina/química , Mucosa Bucal/metabolismo , Nanopartículas/química , Administración Oral , Secuencia de Aminoácidos , Animales , Transporte Biológico , Péptidos de Penetración Celular/química , Difusión , Portadores de Fármacos/síntesis química , Epitelio/metabolismo , Células HT29 , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/farmacología , Insulina/farmacocinética , Insulina/farmacología , Espacio Intracelular/metabolismo , Masculino , Datos de Secuencia Molecular , Permeabilidad , Ácidos Polimetacrílicos/química , Ratas , Ratas Sprague-Dawley
18.
J Biomed Nanotechnol ; 11(5): 865-76, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-26349398

RESUMEN

The purpose of this study was to formulate nanoparticles with an elaborate structure for oral delivery of exendin-4 using a simple preparation process. The nanoparticles possessed a mixed lipid shell and an aqueous core which contained drug-loaded micelles. Formulation was optimized by a central composite design and the structure of the nanoparticles was validated. The efficacy for delivery of exendin-4 was evaluated both in vitro and in vivo. The drug encapsulation efficiency of the nanoparticles reached 97.7%. The nanoparticles greatly enhanced the cellular uptake and transport of encapsulated exendin-4 in vitro. The in situ study showed that exendin-4 could be transported across the epithelium into intestinal capillaries, while the lipid materials largely remained in the epithelium. Pharmacodynamic studies in diabetic KKAy mice demonstrated that the exendin-4-loaded nanoparticles exhibited a marked hypoglycemia effect with a pharmacological availability of 12.7% after intestinal administration.


Asunto(s)
Hipoglucemiantes , Absorción Intestinal , Nanopartículas , Péptidos/administración & dosificación , Péptidos/farmacocinética , Ponzoñas/administración & dosificación , Ponzoñas/farmacocinética , Animales , Células CACO-2 , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Portadores de Fármacos/química , Exenatida , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacocinética , Absorción Intestinal/efectos de los fármacos , Liposomas/química , Masculino , Ratones , Ratones Obesos , Ratones Transgénicos , Micelas , Nanopartículas/metabolismo , Ratas , Ratas Sprague-Dawley , Agua/química
19.
Adv Healthc Mater ; 4(8): 1203-14, 2015 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-25800699

RESUMEN

A novel blended nanoparticle (NP) system for the delivery of anticancer drugs and its surprisingly high efficacy for cancer chemotherapy by blending a targeting polymer folic acid-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (FA-PEG-b-PLGA) and a miscible structurally similar polymer D-α-tocopheryl polyethylene glycol 1000 succinate-poly(lactide-co-glycolide) (TPGS-PLGA) is reported. This blended NP system can be achieved through a simple and effective nanoprecipitation technique, and possesses unique properties: i) improved long-term compatibility brought by PEG-based polymers; ii) reduced multidrug resistance mediated by P-glycoprotein (P-gp) in tumor cells and increased bioavailability of anticancer drugs by incorporation of TPGS; iii) the regulation of controlled release through polymer ratios and active targeting by FA. Both in vitro cell experiments and in vivo antitumor assays demonstrated the reported blended NP system can achieve the best therapeutic efficiency in an extremely safe, simple and highly efficient process for cancer therapy. Moreover, this NP system is highly efficient in forming NPs with multiple functions, without repeated chemical modification of polymers, which is sometimes complex, inefficient and high cost. Therefore, the development of this novel blended NP concept is extremely meaningful for the application of pharmaceutical nanotechnology in recent studies.


Asunto(s)
Nanopartículas/química , Neoplasias/terapia , Polímeros/química , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Materiales Biocompatibles/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Docetaxel , Sistemas de Liberación de Medicamentos , Resistencia a Antineoplásicos , Endocitosis/efectos de los fármacos , Femenino , Ácido Fólico/química , Células HeLa , Humanos , Células MCF-7 , Ratones , Ratones SCID , Tamaño de la Partícula , Polietilenglicoles/química , Poliglactina 910/química , Ácido Poliglicólico/química , Taxoides/farmacología , Vitamina E/química
20.
Sci Rep ; 4: 4406, 2014 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-24638208

RESUMEN

Metal-enhanced fluorescence of conjugated polyelectrolytes (CPs) is realized using a simple, green hybrid Ag nanocomposite film. Ag nanoparticles (Ag NPs) are pre-prepared by sodium citrate reduction and incorporated into agarose by mixing to form an Ag-containing agarose film (Ag@agarose). Through variation of the amount of Ag NPs in the Ag@agarose film as well as the thickness of the interlayer between CPs and the Ag@agarose film prepared of layer-by-layer assembly of chitosan and sodium alginate, a maximum 8.5-fold increase in the fluorescence of CPs is obtained. After introducing tyrosinase, this system also can be used to detect phenolic compounds with high sensitivity and good visualization under ultraviolet light.


Asunto(s)
Nanopartículas del Metal/química , Nanocompuestos/química , Fenoles/análisis , Plata/química , Espectrometría de Fluorescencia/métodos , Alginatos/química , Quitosano/química , Citratos/química , Fluorescencia , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Monofenol Monooxigenasa/química , Oxidación-Reducción , Polietileneimina/química , Compuestos de Amonio Cuaternario/química , Quinonas/química , Sefarosa/química , Citrato de Sodio , Soluciones , Rayos Ultravioleta
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