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1.
Int J Nanomedicine ; 16: 2585-2595, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33833513

RESUMEN

Background: In cancer nanomedicine, drugs are transported by nanocarriers through a biological system to produce a therapeutic effect. The efficacy of the treatment is affected by the ability of the nanocarriers to overcome biological transport barriers to reach their target. In this work, we focus on the process of nanocarrier penetration through tumour tissue after extravasation. Visualising the dynamics of nanocarriers in tissue is difficult in vivo, and in vitro assays often do not capture the spatial and physical constraints relevant to model tissue penetration. Methods: We propose a new simple, low-cost method to observe the transport dynamics of nanoparticles through a tissue-mimetic microfluidic chip. After loading a chip with triplicate conditions of gel type and loading with microparticles, microscopic analysis allows for tracking of fluorescent nanoparticles as they move through hydrogels (Matrigel and Collagen I) with and without cell-sized microparticles. A bespoke image-processing codebase written in MATLAB allows for statistical analysis of this tracking, and time-dependent dynamics can be determined. Results: To demonstrate the method, we show size-dependence of transport mechanics can be observed, with diffusion of fluorescein dye throughout the channel in 8 h, while 20 nm carboxylate FluoSphere diffusion was hindered through both Collagen I and Matrigel™. Statistical measurements of the results are generated through the software package and show the significance of both size and presence of microparticles on penetration depth. Conclusion: This provides an easy-to-understand output for the end user to measure nanoparticle tissue penetration, enabling the first steps towards future automated experimentation of transport dynamics for rational nanocarrier design.


Asunto(s)
Geles/química , Microfluídica/métodos , Nanopartículas/administración & dosificación , Nanopartículas/metabolismo , Andamios del Tejido/química , Colágeno/química , Colágeno/metabolismo , Difusión , Humanos , Nanomedicina/métodos , Nanopartículas/química
2.
Int J Nanomedicine ; 16: 2597-2613, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33833514

RESUMEN

Introduction: Limited by tumor vascular barriers, restricted intratumoural T cell infiltration and nanoparticles accumulation remain major bottlenecks for anticancer therapy. Platelets are now known to maintain tumor vascular integrity. Therefore, inhibition of tumor-associated platelets may be an effective method to increase T cell infiltration and drug accumulation at tumor sites. Herein, we designed an ultrasound-responsive nitric oxide (NO) release nanosystem, SNO-HSA-PTX, which can release NO in response to ultrasound (US) irradiation, thereby inhibiting platelet function and opening the tumor vascular barrier, promoting drug accumulation and T cell infiltration. Methods: We evaluated the ability of SNO-HSA-PTX to release NO in response to US irradiation. We also tested the effect of SNO-HSA-PTX on platelet function. Plenty of studies including cytotoxicity, pharmacokinetics study, biodistribution, blood perfusion, T cell infiltration, in vivo antitumor efficacy and safety assessment were conducted to investigate the antitumor effect of SNO-HSA-PTX. Results: SNO-HSA-PTX with US irradiation inhibited tumor-associated platelets activation and induced openings in the tumor vascular barriers, which promoted the accumulation of SNO-HSA-PTX nanoparticles to the tumor sites. Meanwhile, the damaged vascular barriers allowed oxygen-carrying hemoglobin to infiltrate tumor regions, alleviating hypoxia of the tumor microenvironment. In addition, the intratumoral T cell infiltration was augmented, together with chemotherapy and NO therapy, which greatly inhibited tumor growth. Discussion: Our research designed a simple strategy to open the vascular barrier by inhibiting the tumor-associated platelets, which provide new ideas for anti-tumor treatment.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Linfocitos Infiltrantes de Tumor/inmunología , Nanopartículas/administración & dosificación , Óxido Nítrico/metabolismo , Compuestos Nitrosos/química , Paclitaxel/farmacología , Albúmina Sérica Humana/química , Ondas Ultrasónicas , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/farmacología , Apoptosis , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/química , Paclitaxel/administración & dosificación , Paclitaxel/farmacocinética , Distribución Tisular , Células Tumorales Cultivadas , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Int J Mol Sci ; 22(6)2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33805602

RESUMEN

Carriers of genetic material are divided into vectors of viral and non-viral origin. Viral carriers are already successfully used in experimental gene therapies, but despite advantages such as their high transfection efficiency and the wide knowledge of their practical potential, the remaining disadvantages, namely, their low capacity and complex manufacturing process, based on biological systems, are major limitations prior to their broad implementation in the clinical setting. The application of non-viral carriers in gene therapy is one of the available approaches. Poly(amidoamine) (PAMAM) dendrimers are repetitively branched, three-dimensional molecules, made of amide and amine subunits, possessing unique physiochemical properties. Surface and internal modifications improve their physicochemical properties, enabling the increase in cellular specificity and transfection efficiency and a reduction in cytotoxicity toward healthy cells. During the last 10 years of research on PAMAM dendrimers, three modification strategies have commonly been used: (1) surface modification with functional groups; (2) hybrid vector formation; (3) creation of supramolecular self-assemblies. This review describes and summarizes recent studies exploring the development of PAMAM dendrimers in anticancer gene therapies, evaluating the advantages and disadvantages of the modification approaches and the nanomedicine regulatory issues preventing their translation into the clinical setting, and highlighting important areas for further development and possible steps that seem promising in terms of development of PAMAM as a carrier of genetic material.


Asunto(s)
Dendrímeros/síntesis química , Regulación Neoplásica de la Expresión Génica , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Proteínas de Neoplasias/antagonistas & inhibidores , Neoplasias/terapia , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/síntesis química , Dendrímeros/administración & dosificación , Regulación Gubernamental , Humanos , MicroARNs/administración & dosificación , MicroARNs/genética , MicroARNs/metabolismo , Nanomedicina/legislación & jurisprudencia , Nanomedicina/métodos , Nanopartículas/administración & dosificación , Nanopartículas/química , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Oligonucleótidos Antisentido/administración & dosificación , Oligonucleótidos Antisentido/genética , Oligonucleótidos Antisentido/metabolismo , Plásmidos/administración & dosificación , Plásmidos/química , Plásmidos/metabolismo , ARN Mensajero/administración & dosificación , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Propiedades de Superficie
4.
AAPS PharmSciTech ; 22(3): 133, 2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33855636

RESUMEN

Luteolin suffers from drawbacks like low solubility and bioavailability, thus hindering its application in the clinic. In this study, we employed sodium dodecyl sulfate (SDS), an efficient tight junction opening agent, to modify the surface of luteolin nanocrystals, aiming to enhance the bioavailability of luteolin (LUT) and luteolin nanocrystals (LNC). The particle sizes of SDS-modified luteolin nanocrystals (SLNC) were slightly larger than that of LNC, and the zeta potential of LNC and SLNC was -25.0 ± 0.7 mV and -43.5 ± 0.4 mV, respectively. Both LNC and SLNC exhibited enhanced saturation solubility and high stability in the liquid state. In the cellular study, we found that SDS has cytotoxicity on caco-2 cells and could open the tight junction of the caco-2 monolayer, which could lead to an enhanced transport of luteolin across the intestinal membrane. The bioavailability of luteolin was enhanced for 1.90-fold by luteolin nanocrystals, and after modification with SDS, the bioavailability was enhanced to 3.48-fold. Our experiments demonstrated that SDS could efficiently open the tight junction and enhance the bioavailability of luteolin thereafter, revealing the construction of SDS-modified nanocrystals is a good strategy for enhancing the oral bioavailability of poorly soluble drugs like luteolin.


Asunto(s)
Luteolina/síntesis química , Luteolina/farmacocinética , Nanopartículas/química , Nanopartículas/metabolismo , Dodecil Sulfato de Sodio/síntesis química , Dodecil Sulfato de Sodio/farmacocinética , Administración Oral , Animales , Disponibilidad Biológica , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Humanos , Luteolina/administración & dosificación , Masculino , Nanopartículas/administración & dosificación , Tamaño de la Partícula , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Dodecil Sulfato de Sodio/administración & dosificación , Solubilidad , Propiedades de Superficie
5.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-33806499

RESUMEN

Diabetic nephropathy (DN) ranks among the most detrimental long-term effects of diabetes, affecting more than 30% of all patients. Within the diseased kidney, intraglomerular mesangial cells play a key role in facilitating the pro-fibrotic turnover of extracellular matrix components and a progredient glomerular hyperproliferation. These pathological effects are in part caused by an impaired functionality of soluble guanylate cyclase (sGC) and a consequentially reduced synthesis of anti-fibrotic messenger 3',5'-cyclic guanosine monophosphate (cGMP). Bay 58-2667 (cinaciguat) is able to re-activate defective sGC; however, the drug suffers from poor bioavailability and its systemic administration is linked to adverse events such as severe hypotension, which can hamper the therapeutic effect. In this study, cinaciguat was therefore efficiently encapsulated into virus-mimetic nanoparticles (NPs) that are able to specifically target renal mesangial cells and therefore increase the intracellular drug accumulation. NP-assisted drug delivery thereby increased in vitro potency of cinaciguat-induced sGC stabilization and activation, as well as the related downstream signaling 4- to 5-fold. Additionally, administration of drug-loaded NPs provided a considerable suppression of the non-canonical transforming growth factor ß (TGF-ß) signaling pathway and the resulting pro-fibrotic remodeling by 50-100%, making the system a promising tool for a more refined therapy of DN and other related kidney pathologies.


Asunto(s)
Benzoatos/administración & dosificación , Sistemas de Liberación de Medicamentos , Células Mesangiales/efectos de los fármacos , Células Mesangiales/metabolismo , Guanilil Ciclasa Soluble/metabolismo , Animales , Benzoatos/farmacocinética , Materiales Biomiméticos , Células Cultivadas , GMP Cíclico/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Activación Enzimática/efectos de los fármacos , Estabilidad de Enzimas/efectos de los fármacos , Fibrosis , Humanos , Células Mesangiales/patología , Modelos Biológicos , Nanopartículas/administración & dosificación , Ratas , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo
6.
Int J Nanomedicine ; 16: 2389-2404, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33790556

RESUMEN

Recently, there has been an incredible increase in research about the abnormal growth of cells (neoplasm), focusing on the management, treatment and preventing reoccurrence. It has been understood that the natural defense system, composed of a variety of immune defensive cells, does not just limit its function in eliminating neoplastic cells, but also controls the growth and spread of tumor cells of different kinds to other parts of the body. Cancer immunotherapy, is a cancer treatment plan that educates the body's defensive system to forestall, control, and eliminate tumor cells. The effectiveness of immunotherapy is achieved, to its highest efficacy, by the use of nanoparticles (NPs) for precise and timely delivery of immunotherapies to specific targeted neoplasms, with less or no harm to the healthy cells. Immunotherapies have been affirmed in clinical trials as a cancer regimen for various types of cancers, the side effects resulting from imprecise and non-targeted conveyance is well managed with the use of nanoparticles. Nonetheless, we will concentrate on enhancing cancer immunotherapy approaches by the use of nanoparticles for the productivity of antitumor immunity. Nanoparticles will be presented and utilized as an objective immunotherapy delivery system for high exactness and are thus a promising methodology for cancer treatment.


Asunto(s)
Sistemas de Liberación de Medicamentos , Objetivos , Inmunoterapia , Nanopartículas/química , Neoplasias/inmunología , Neoplasias/terapia , Animales , Humanos , Nanopartículas/administración & dosificación
7.
Int J Nanomedicine ; 16: 1553-1564, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33658783

RESUMEN

Purpose: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Most current therapeutic strategies primarily include localized treatment, lacking effective systemic strategies. Meanwhile, recent studies have suggested that RNA vaccines can effectively activate antigen-presenting cells (APCs) and lymphocytes to produce a strong systemic immune response and inhibit tumor growth. However, tumor vaccines loaded with a single tumor antigen may induce immunosuppression and immune evasion, while identifying tumor-specific antigens can require expensive and laborious procedures. Therefore, the use of whole tumor cell antigens are currently considered to be promising, potentially effective, methods. Previously, we developed a targeted liposome-polycation-DNA (LPD) complex nanoparticle that possess a small size, high RNA encapsulation efficiency, and superior serum stability. These particles were found to successfully deliver RNA to tumor sites. In the current study, we encapsulated total tumor-derived RNA in lipid nanoparticles (LNPs) to target dendritic cells (DCs) to incite expeditious and robust anti-tumor immunity. Methods: Total tumor-derived RNA was extracted from liver cancer cells (Hepa1-6 cells). LNPs loaded with tumor RNA were then prepared thin-film hydration method. The ability of RNA LNPs to induce DC maturation, cytotoxicity, and anti-tumor activity, was investigated in vitro and in vivo. Results: The average particle size of LNPs and RNA LNPs was 102.22 ± 4.05 nm and 209.68 ± 6.14 nm, respectively, while the zeta potential was 29.97 ± 0.61 mV and 42.03 ± 0.42 mV, respectively. Both LNPs and RNA LNP vaccines exhibited good distribution and stability. In vitro, RNA LNP vaccines were capable of promoting DC maturation and inducing T lymphocytes to kill Hepa1-6 cells. In vivo, RNA LNP vaccines effectively prevent and inhibit HCC growth. Conclusion: RNA LNPs may serve as an effective antigen specific vaccine to induce anti-tumor immunity for HCC.


Asunto(s)
Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/terapia , Inmunoterapia , Lípidos/química , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/terapia , Nanopartículas/química , ARN Neoplásico/metabolismo , Animales , Vacunas contra el Cáncer/inmunología , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Humanos , Activación de Linfocitos/inmunología , Masculino , Ratones Endogámicos C57BL , Nanopartículas/administración & dosificación , Tamaño de la Partícula , Linfocitos T/inmunología
8.
AAPS PharmSciTech ; 22(3): 89, 2021 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-33665749

RESUMEN

It is well known that neutrophil-mediated delivery of therapeutic agents is a promising method for treating tumors. However, owing to the limited number and limited uptake ability of neutrophils, determining a reasonable dose has become an urgent problem to be solved. Furthermore, the number of nanoparticles is far greater than the number of neutrophils at normal doses, which causes excessive nanoparticles to reach nontargeted organs or tissues, leading to serious adverse effects. To address these problems, a neutrophil-targeting delivery system (DiR-DADGC-L) based on DiR-labeled and butanedioic acid (DA)-linked 5-amino-3,5-dideoxy-D-Glycerol-D-galactonanulose-cholesterol conjugate (DADGC) was designed to improve the efficiency of hitchhiking neutrophils through the specific binding of sialic acid (SA) to L-selectin (SA-binding receptor, expressed on neutrophils). DiR-DADGC-L was prepared with favorable particle size and encapsulation efficiency (%EE) to deliver DiR into neutrophils. Subsequently, diverse doses of DiR-DADGC-L were injected intravenously into S180 tumor-bearing and cyclophosphamide-depleted (CTX-D) S180 tumor-bearing mice to evaluate the in vivo behavior of liposomes. The results verified the following: a) The content of DiR-DADGC-L in neutrophils accounts for approximately 14.5% of the content of DiR-DADGC-L in plasma, and the uptake capacity of neutrophils remains unchanged under different doses, and b) both neutrophils and the enhanced permeability and retention (EPR) effect might exert significant roles in tumor treatment. As for the neutrophil-mediated delivery system, higher doses are not necessarily appropriate, and a lower dose may achieve an unexpected effect. It will be wise to determine an optimum dose to improve delivery efficiency.


Asunto(s)
Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Nanopartículas/administración & dosificación , Neoplasias/tratamiento farmacológico , Neutrófilos/metabolismo , Animales , Antineoplásicos/farmacocinética , Ciclofosfamida/administración & dosificación , Ciclofosfamida/farmacocinética , Ciclofosfamida/uso terapéutico , Sistemas de Liberación de Medicamentos , Selectina L/metabolismo , Liposomas , Masculino , Ratones , Ácido N-Acetilneuramínico/metabolismo , Tamaño de la Partícula , Sarcoma 180/tratamiento farmacológico , Distribución Tisular
9.
Int J Nanomedicine ; 16: 1743-1755, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33688189

RESUMEN

Background: As a therapeutic target for cancer treatment, HSP90 has been explored extensively. However, the significant side effects of the HSP90 inhibitor 17AAG have limited its clinical use. Methods: In this study, we used hyaluronic acid (HA)-decorated DOTAP-PLGA hybrid nanoparticles (HA-DOTAP-PLGA NPs) as 17AAG-delivery carriers for targeted colon cancer therapy. Results: Different methods were used to characterize the successful fabrication of these hybrid PLGA NPs. Our results demonstrated that internalization of HA-NPs in colon cancer cells was governed by CD44receptor-mediated endocytosis. Annexin V-propidium iodide staining experiments revealed that cell apoptosis induced by HA-NPs-17AAG in colon cancer cells was more efficient than free 17AAG. In two animal models used to screen anticancer efficacy (Luc-HT29 subcutaneous xenograft and AOM/DSS-induced orthotopic tumor model), HA-NPs-17AAG significantly inhibited xenograft and orthotopic tumor growth, demonstrating HA-NPs-17AAG had much better therapeutic efficiency than free 17AAG. It is worth noting that great biocompatibility of HA-DOTAP-PLGA NPs was observed both in vitro and in vivo. Conclusion: Our research offers a preclinical proof of concept for colon cancer therapy with DOTAP-PLGA NPs as a creative drug-delivery system.


Asunto(s)
Neoplasias del Colon/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Ácido Hialurónico/química , Nanopartículas/química , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Benzoquinonas/farmacología , Materiales Biocompatibles/química , Línea Celular Tumoral , Neoplasias del Colon/patología , Endocitosis/efectos de los fármacos , Ácidos Grasos Monoinsaturados/química , Fluorescencia , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Receptores de Hialuranos/metabolismo , Lactamas Macrocíclicas/farmacología , Ratones , Nanopartículas/administración & dosificación , Nanopartículas/ultraestructura , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Compuestos de Amonio Cuaternario/química , Tejido Subcutáneo/efectos de los fármacos , Tejido Subcutáneo/patología
10.
Life Sci ; 274: 119344, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33716062

RESUMEN

AIMS: Amiodarone (AM) is a highly efficient drug for arrhythmias treatment, but its extra-cardiac adverse effects offset its therapeutic efficacy. Nanoparticles (NPs)-based delivery system could provide a strategy to allow sustained delivery of AM to the myocardium and reduction of adverse effects. The primary purpose was to develop AM-loaded NPs and explore their ameliorative effects versus off-target toxicities. MATERIALS AND METHODS: Polymeric NPs were prepared using poly lactic-co-glycolic acid and their physicochemical properties were characterized. Animal studies were conducted using a rat model to compare exposure to AM versus that of the AM-loaded NPs. Biochemical evaluation of liver enzymes, lipid profile, and thyroid hormones was achieved. Besides, histopathological changes in liver and lung were studied. KEY FINDINGS: Under optimal experimental conditions, the AM-loaded NPs had a size of 186.90 nm and a negative zeta potential (-14.67 mV). Biochemical evaluation of AM-treated animal group showed a significant increase in cholesterol, TG, LDL, T4, and TSH levels (ρ < 0.05). Remarkably, the AM-treated group exhibited a significant increase of liver enzymes (ρ < 0.05) coupled with an obvious change in liver architecture. The AM-loaded NPs displayed a reduction of liver damage and enzyme levels. Lung sections of the AM-treated group demonstrated thickening of interalveolar septa, mononuclear cellular infiltration with congested blood vessels, and heavy collagenous fibers deposition. Conversely, less cellular infiltration and septal thickening were observed in the animal lungs treated with the AM-loaded NPs-treated. SIGNIFICANCE: Our findings demonstrate the competence of the AM-loaded NPs to open several exciting avenues for evading the AM-induced off-target toxicities.


Asunto(s)
Amiodarona/química , Amiodarona/farmacología , Portadores de Fármacos/química , Hígado/patología , Nanopartículas/toxicidad , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Amiodarona/administración & dosificación , Animales , Antiarrítmicos/administración & dosificación , Antiarrítmicos/química , Antiarrítmicos/farmacología , Hígado/efectos de los fármacos , Masculino , Nanopartículas/administración & dosificación , Estudios Prospectivos , Ratas , Ratas Sprague-Dawley , Pruebas de Toxicidad
11.
Ecotoxicol Environ Saf ; 214: 112113, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33690006

RESUMEN

The main purpose of this work is to thoroughly describe the implementation protocol of laser-induced breakdown spectroscopy (LIBS) method in the plant analysis. Numerous feasibility studies and recent progress in instrumentation and trends in chemical analysis make LIBS an established method in plant bioimaging. In this work, we present an easy and straightforward phytotoxicity case study with a focus on LIBS method. We intend to demonstrate in detail how to manipulate with plants after exposures and how to prepare them for analyses. Moreover, we aim to achieve 2D maps of spatial element distribution with a good resolution without any loss of sensitivity. The benefits of rapid, low-cost bioimaging are highlighted. In this study, cabbage (Brassica oleracea L.) was treated with an aqueous dispersion of photon-upconversion nanoparticles (NaYF4 doped with Yb3+ and Tm3+ coated with carboxylated silica shell) in a hydroponic short-term toxicity test. After a 72-hour plant exposure, several macroscopic toxicity end-points were monitored. The translocation of Y, Yb, and Tm across the whole plant was set by employing LIBS with a lateral resolution 100 µm. The LIBS maps of rare-earth elements in B.oleracea plant grown with 50 µg/mL nanoparticle-treated and ion-treated exposures showed the root as the main storage, while the transfer via stem into leaves was minimal. On the contrary, the LIBS maps of plants exposed to the 500 µg/mL nanoparticle-treated and ion-treated uncover slightly different trends, nanoparticles as well as ions were transferred through the stem into leaves. However, the main storage organ was a root as well.


Asunto(s)
Brassica/metabolismo , Fluoruros/administración & dosificación , Nanopartículas/administración & dosificación , Dióxido de Silicio/administración & dosificación , Tulio/toxicidad , Iterbio/administración & dosificación , Itrio/administración & dosificación , Rayos Láser , Hojas de la Planta/metabolismo , Raíces de Plantas/metabolismo , Tallos de la Planta/metabolismo , Análisis Espectral
12.
AAPS PharmSciTech ; 22(3): 113, 2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33751276

RESUMEN

The present research focuses on the development of a nanoparticulate (nanocrystals-loaded) rapidly dissolving (orodispersible) tablet with improved solubility and bioavailability. The nanosuspension (NS) was prepared by antisolvent sonoprecipitation technique and the optimized NS was lyophilized to obtain nanocrystals (NCs), which were evaluated for various parameters. The nitrendipine (NIT) nanoparticulate orodispersible tablet (N-ODT) was prepared by direct compression method. The optimized N-ODT was evaluated for pre and post compression characteristics, in vivo pharmacokinetic and stability profile. The optimized NS showed a particle size of 505.74 ± 15.48 nm with a polydispersity index (PDI) of 0.083 ± 0.006. The % NIT content in the NCs was found to be 78.4 ± 2.3%. The saturation solubility of NIT was increased remarkably (26.14 times) in comparison to plain NIT, post NCs development. The DSC and p-XRD analysis of NCs revealed the perseverance of the integrity and crystallinity of NIT on lyophilization. The results of micromeritic studies revealed the good flow-ability and compressibility of NCs blend. All the post-compression properties of N-ODT were observed within the standard intended limit. The dispersion, wetting, and disintegration time of the optimized batch of N-ODT was found to be 39 ± 1.13 s, 44.66 ± 1.52 s, and 33.91 ± 0.94 s respectively. The in vitro dissolution study displayed 100.28 ± 2.64% and 100.61 ± 3.3% of NIT released from NCs (in 8 min) and N-ODT (in 6 min) respectively, while conventional NIT tablet took 30 min to release 99.94 ± 1.57% of NIT. The in vivo pharmacokinetic study in rabbits demonstrated significantly (p < 0.05) higher bioavailability of NIT on release from N-ODT than the conventional NIT tablet. Thus, N-ODT could be a promising tool for improving the solubility and bioavailability of NIT and to treat cardiovascular diseases effectively.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Desarrollo de Medicamentos/métodos , Nanopartículas/química , Nanopartículas/metabolismo , Nitrendipino/síntesis química , Nitrendipino/farmacocinética , Administración Oral , Animales , Disponibilidad Biológica , Liberación de Fármacos/fisiología , Masculino , Nanopartículas/administración & dosificación , Nitrendipino/administración & dosificación , Tamaño de la Partícula , Conejos , Solubilidad , Difracción de Rayos X/métodos
13.
AAPS PharmSciTech ; 22(3): 114, 2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33763759

RESUMEN

Lisofylline (LSF) is an anti-inflammatory molecule with high aqueous solubility and rapid metabolic interconversion to its parent drug, pentoxifylline (PTX) resulting in very poor pharmacokinetic (PK) parameters, necessitating high dose and dosing frequency. In the present study, we resolved the physicochemical and pharmacokinetic limitations associated with LSF and designed its oral dosage form as a tablet for effective treatment in type 1 diabetes (T1D). Self-assembling polymeric micelles of LSF (lisofylline-linoleic acid polymeric micelles (LSF-LA PLM)) were optimized for scale-up (6 g batch size) and lyophilized followed by compression into tablets. Powder blend and tablets were evaluated as per USP. LSF-LA PLM tablet so formed was evaluated for in vitro release in simulated biological fluids (with enzymes) and for cell viability in MIN-6 cells. LSF-LA PLM in tablet formulation was further evaluated for intestinal permeability (in situ) along with LSF and LSF-LA self-assembled micelles (SM) as controls in a rat model using single-pass intestinal perfusion (SPIP) study. SPIP studies revealed 1.8-fold higher oral absorption of LSF-LA from LSF-LA PLM as compared to LSF-LA SM and ~5.9-fold higher than LSF (alone) solution. Pharmacokinetic studies of LSF-LA PLM tablet showed greater Cmax than LSF, LSF-LA, and LSF-LA PLM. Designed facile LSF-LA PLM tablet dosage form has potential for an immediate decrease in the postprandial glucose levels in patients of T1D.


Asunto(s)
Diabetes Mellitus Tipo 1/metabolismo , Yeyuno/metabolismo , Ácido Linoleico/farmacocinética , Nanopartículas/metabolismo , Pentoxifilina/análogos & derivados , Perfusión/métodos , Administración Oral , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Formas de Dosificación , Yeyuno/efectos de los fármacos , Ácido Linoleico/administración & dosificación , Ácido Linoleico/síntesis química , Masculino , Ratones , Nanopartículas/administración & dosificación , Nanopartículas/química , Pentoxifilina/administración & dosificación , Pentoxifilina/síntesis química , Pentoxifilina/farmacocinética , Ratas , Ratas Wistar , Comprimidos
14.
Int J Mol Sci ; 22(4)2021 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-33670545

RESUMEN

Microfluidics is a relatively newly emerged field based on the combined principles of physics, chemistry, biology, fluid dynamics, microelectronics, and material science. Various materials can be processed into miniaturized chips containing channels and chambers in the microscale range. A diverse repertoire of methods can be chosen to manufacture such platforms of desired size, shape, and geometry. Whether they are used alone or in combination with other devices, microfluidic chips can be employed in nanoparticle preparation, drug encapsulation, delivery, and targeting, cell analysis, diagnosis, and cell culture. This paper presents microfluidic technology in terms of the available platform materials and fabrication techniques, also focusing on the biomedical applications of these remarkable devices.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Técnicas Analíticas Microfluídicas/métodos , Microfluídica/métodos , Nanopartículas/administración & dosificación , Preparaciones Farmacéuticas/administración & dosificación , Animales , Técnicas de Cultivo de Célula/instrumentación , Técnicas de Cultivo de Célula/métodos , Ensayos Analíticos de Alto Rendimiento/instrumentación , Ensayos Analíticos de Alto Rendimiento/métodos , Humanos , Técnicas Analíticas Microfluídicas/instrumentación , Microfluídica/instrumentación , Biología Molecular/instrumentación , Biología Molecular/métodos , Nanopartículas/química
15.
Artif Cells Nanomed Biotechnol ; 49(1): 204-218, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33645342

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoo tonic, highly pathogenic virus. The new type of coronavirus with contagious nature spread from Wuhan (China) to the whole world in a very short time and caused the new coronavirus disease (COVID-19). COVID-19 has turned into a global public health crisis due to spreading by close person-to-person contact with high transmission capacity. Thus, research about the treatment of the damages caused by the virus or prevention from infection increases everyday. Besides, there is still no approved and definitive, standardized treatment for COVID-19. However, this disaster experienced by human beings has made us realize the significance of having a system ready for use to prevent humanity from viral attacks without wasting time. As is known, nanocarriers can be targeted to the desired cells in vitro and in vivo. The nano-carrier system targeting a specific protein, containing the enzyme inhibiting the action of the virus can be developed. The system can be used by simple modifications when we encounter another virus epidemic in the future. In this review, we present a potential treatment method consisting of a nanoparticle-ribozyme conjugate, targeting ACE-2 receptors by reviewing the virus-associated ribozymes, their structures, types and working mechanisms.


Asunto(s)
/tratamiento farmacológico , Nanopartículas/administración & dosificación , ARN Catalítico/uso terapéutico , ARN Viral/antagonistas & inhibidores , /efectos de los fármacos , /antagonistas & inhibidores , Ensayos Clínicos como Asunto , Portadores de Fármacos , Composición de Medicamentos , Diseño de Fármacos , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Modelos Moleculares , Conformación de Ácido Nucleico , Interferencia de ARN , ARN Catalítico/administración & dosificación , ARN Catalítico/química , ARN Catalítico/clasificación , ARN no Traducido/clasificación , ARN no Traducido/genética , ARN no Traducido/uso terapéutico , Virus del SRAS/efectos de los fármacos , Virus del SRAS/genética , /fisiología , Glicoproteína de la Espiga del Coronavirus/fisiología , Replicación Viral/efectos de los fármacos
16.
Life Sci ; 276: 119436, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-33789146

RESUMEN

Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Movimiento Celular , Proliferación Celular , Cristales Líquidos/química , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas/administración & dosificación , Rutina/farmacología , Células A549 , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/patología , Nanopartículas/química , Rutina/administración & dosificación , Rutina/química
17.
Nat Commun ; 12(1): 759, 2021 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-33536421

RESUMEN

The malignancy of colorectal cancer (CRC) is connected with inflammation and tumor-associated macrophages (TAMs), but effective therapeutics for CRC are limited. To integrate therapeutic targeting with tumor microenvironment (TME) reprogramming, here we develop biocompatible, non-covalent channel-type nanoparticles (CNPs) that are fabricated through host-guest complexation and self-assemble of mannose-modified γ-cyclodextrin (M-γ-CD) with Regorafenib (RG), RG@M-γ-CD CNPs. In addition to its carrier role, M-γ-CD serves as a targeting device and participates in TME regulation. RG@M-γ-CD CNPs attenuate inflammation and inhibit TAM activation by targeting macrophages. They also improve RG's anti-tumor effect by potentiating kinase suppression. In vivo application shows that the channel-type formulation optimizes the pharmacokinetics and bio-distribution of RG. In colitis-associated cancer and CT26 mouse models, RG@M-γ-CD is proven to be a targeted, safe and effective anti-tumor nanomedicine that suppresses tumor cell proliferation, lesions neovascularization, and remodels TME. These findings indicate RG@M-γ-CD CNPs as a potential strategy for CRC treatment.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Nanopartículas/administración & dosificación , Neoplasias Experimentales/tratamiento farmacológico , Compuestos de Fenilurea/administración & dosificación , Piridinas/administración & dosificación , gamma-Ciclodextrinas/administración & dosificación , Animales , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HT29 , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Manosa/química , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Nanopartículas/química , Neoplasias Experimentales/genética , Neoplasias Experimentales/metabolismo , Compuestos de Fenilurea/química , Piridinas/química , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genética , gamma-Ciclodextrinas/química
19.
Int J Nanomedicine ; 16: 881-893, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33574668

RESUMEN

Purpose: Mesoporous silica (MSNs) have attracted considerable attention for its application in the field of drug delivery and biomedicine due to its high surface area, large pore volume, and low toxicity. Recently, numerous studies revealed that gut microbiota is of critical relevance to host health. However, the toxicological studies of MSNs were mainly based on the degradation, biodistribution, and excretion in mammalian after oral administration for now. Here in this study, we explored the impacts of oral administration of three kinds of MSNs on gut microbiota in rats to assess its potential toxicity. Methods: Forty rats were divided into four groups: control group; Mobil Composition of Matter No. 41 type mesoporous silica (MCM-41) group; Santa Barbara Amorphous-15 type mesoporous silica (SBA-15) group, and biodegradable dendritic center-radial mesoporous silica nanoparticle (DMSN) group. Fecal samples were collected 3 days and 7 days after the intake of MSNs and analyzed with high throughput sequencing. Gastric tissues in rats were obtained after dissection for the histological study. Results: Three different MSNs (MCM-41, SBA-15, and DMSN) were successfully prepared in this study. The pore size of three MSNs was calculated similarly as (3.54 ± 0.15) nm, (3.48 ± 0.21) nm, and (3.45 ± 0.17) nm according to the BET & BJH model, respectively, while the particle size of MCM-41, SBA-15 and DMSN was around 209.2 nm, 1349.56 nm, and 244.4 nm, respectively. In the gene analysis of 16S rRNA, no significant changes in the diversity and richness were found between groups, while Verrucomicrobia decreased and Candidatus Saccharibacteria increased in MCM-41 treated groups. Meanwhile, no inflammatory and erosion symptoms were observed in the morphological analysis of the colons, except the MCM-41 treated group. Conclusion: Three different MSNs, MCM-41, SBA-15, and DMSN were successfully prepared, and this study firstly suggested the impact of MSNs on the gut microbiota, and further revealing the potential pro-inflammatory effects of oral administration of MCM-41 was possibly through the changing of gut microbiota.


Asunto(s)
Colon/microbiología , Colon/patología , Microbioma Gastrointestinal , Inflamación/patología , Nanopartículas/administración & dosificación , Dióxido de Silicio/química , Administración Oral , Animales , Bacterias/genética , Biodiversidad , Microbioma Gastrointestinal/genética , Masculino , Nanopartículas/ultraestructura , Tamaño de la Partícula , Filogenia , Porosidad , Análisis de Componente Principal , ARN Ribosómico 16S/genética , Ratas Sprague-Dawley , Dióxido de Silicio/síntesis química , Distribución Tisular
20.
Cell ; 184(5): 1188-1200.e19, 2021 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-33577765

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission, and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits, and cynomolgus macaques. The vaccine-induced immunity protects macaques against a high-dose challenge, resulting in strongly reduced viral infection and replication in the upper and lower airways. These nanoparticles are a promising vaccine candidate to curtail the SARS-CoV-2 pandemic.


Asunto(s)
/administración & dosificación , Macaca fascicularis , Glicoproteína de la Espiga del Coronavirus/química , Animales , Anticuerpos Neutralizantes , Linfocitos B/inmunología , /prevención & control , Ratones , Ratones Endogámicos BALB C , Modelos Animales , Nanopartículas/administración & dosificación , Conejos , Glicoproteína de la Espiga del Coronavirus/sangre , Linfocitos T/inmunología , Carga Viral
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