Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 858
Filtrar
1.
Int J Nanomedicine ; 16: 2819-2831, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33888982

RESUMEN

Purpose: To investigate the effects of solvents on the formation of self-assembled nanonization of albumin-oleic acid conjugates (AOCs) using a solvent exchange mechanism for the construction of in situ forming implants (ISFI). Methods: A poorly water-soluble drug, paliperidone palmitate (PPP), was chosen as the model drug. AOC was synthesized with the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) reaction. Dichloromethane, tetrahydrofuran, ethanol, N-methyl-2-pyrrolidone, dimethyl sulfoxide, and deionized water were selected to investigate the formation of self-assembled AOC nanoparticles (AONs). The volume ratios of organic solvents against water could determine the miscibility, injectability, and in situ nanonizing capability without aggregation. Results: As the polarity of the organic solvents increased, the AONs exhibited a spherical shape, and the larger the volume of the solvent, the smaller the size of the AONs. To use AOC in ISFI for controlled release of PPP, poly(d,l-lactide-co-glycolide) (PLGA) was combined with the AOC in 2 mL of N-methyl-2-pyrrolidone and water solution (1.8/0.2 ratio). The release rates of all formulations exhibited similar curve patterns overall but were more controlled in decreasing order as follows: AOC, PLGA, and AOC/PLGA for 14 days. Conclusion: A combined formulation of AOC and PLGA was found to effectively control the initial burst release of the drug.


Asunto(s)
Nanopartículas/química , Palmitato de Paliperidona/farmacocinética , Solventes/química , Albúminas/química , Preparaciones de Acción Retardada , Dimetilsulfóxido/química , Implantes de Medicamentos/farmacocinética , Etanol/química , Ácido Oléico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Pirrolidinonas , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Agua
2.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33809846

RESUMEN

Phosphodiesterase 7 (PDE7) is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP), an important cellular messenger. PDE7's role in neurotransmission, expression profile in the brain and the druggability of other phosphodiesterases have motivated the search for potent inhibitors to treat neurodegenerative and inflammatory diseases. Different heterocyclic compounds have been described over the years; among them, phenyl-2-thioxo-(1H)-quinazolin-4-one, called S14, has shown very promising results in different in vitro and in vivo studies. Recently, polymeric nanoparticles have been used as new formulations to target specific organs and produce controlled release of certain drugs. In this work, we describe poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles loaded with S14. Their preparation, optimization, characterization and in vivo drug release profile are here presented as an effort to improve pharmacokinetic properties of this interesting PDE7 inhibitor.


Asunto(s)
Encéfalo/efectos de los fármacos , Preparaciones de Acción Retardada/química , Portadores de Fármacos/química , Nanopartículas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Quinazolinonas/química , Quinazolinonas/farmacocinética , Animales , Encéfalo/metabolismo , Supervivencia Celular/efectos de los fármacos , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 7/antagonistas & inhibidores , Composición de Medicamentos , Liberación de Fármacos , Humanos , Ratones , Estructura Molecular , Nanopartículas/ultraestructura , Tamaño de la Partícula , Permeabilidad
3.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33801871

RESUMEN

Recently, nano- and micro-particulate systems have been widely utilized to deliver pharmaceutical compounds to achieve enhanced therapeutic effects and reduced side effects. Poly (DL-lactide-co-glycolide) (PLGA), as one of the biodegradable polyesters, has been widely used to fabricate particulate systems because of advantages including controlled and sustained release, biodegradability, and biocompatibility. However, PLGA is known for low encapsulation efficiency (%) and insufficient controlled release of water-soluble drugs. It would result in fluctuation in the plasma levels and unexpected side effects of drugs. Therefore, the purpose of this work was to develop microcapsules loaded with alginate-coated chitosan that can increase the encapsulation efficiency of the hydrophilic drug while exhibiting a controlled and sustained release profile with reduced initial burst release. The encapsulation of nanoparticles in PLGA microcapsules was done by the emulsion solvent evaporation method. The encapsulation of nanoparticles in PLGA microcapsules was confirmed by scanning electron microscopy and confocal microscopy. The release profile of hydrophilic drugs can further be altered by the chitosan coating. The chitosan coating onto alginate exhibited a less initial burst release and sustained release of the hydrophilic drug. In addition, the encapsulation of alginate nanoparticles and alginate nanoparticles coated with chitosan in PLGA microcapsules was shown to enhance the encapsulation efficiency of a hydrophilic drug. Based on the results, this delivery system could be a promising platform for the high encapsulation efficiency and sustained release with reduced initial burst release of the hydrophilic drug.


Asunto(s)
Preparaciones de Acción Retardada/farmacocinética , Nanopartículas/química , Preparaciones Farmacéuticas/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacocinética , Alginatos/química , Biodegradación Ambiental , Cápsulas , Quitosano/química , Preparaciones de Acción Retardada/química , Portadores de Fármacos , Liberación de Fármacos , Interacciones Hidrofóbicas e Hidrofílicas , Microscopía Electrónica de Rastreo , Microesferas , Nanopartículas/ultraestructura , Tamaño de la Partícula , Preparaciones Farmacéuticas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química
4.
Int J Nanomedicine ; 16: 1405-1422, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33658780

RESUMEN

Aim: Iridoid glycosides (IG) as the major active fraction of Syringa oblata Lindl. has a proven anti-inflammatory effect for ulcerative colitis (UC). However, its current commercial formulations are hampered by low bioavailability and unable to reach inflamed colon. To overcome the limitation, dual functional IG-loaded nanoparticles (DFNPs) were prepared to increase the residence time of IG in colon. The protective mechanism of DFNPs on DSS-induced colonic injury was evaluated in rats. Materials and Methods: We prepared DFNPs using the oil-in-water emulsion method. PLGA was selected as sustained-release polymer, and ES100 and EL30D-55 as pH-responsive polymers. The morphology and size distribution of NPs were measured by SEM and DLS technique. To evaluate colon targeting of DFNPs, DiR, was encapsulated as a fluorescent probe into NPs. Fluorescent distribution of NPs were investigated. The therapeutic potential and in vivo transportation of NPs in gastrointestinal tract were evaluated in a colitis model. Results: SEM images and zeta data indicated the successful preparation of DFNPs. This formulation exhibited high loading capacity. Drug release results suggested DFNPs released less than 20% at the first 6 h in simulated gastric fluid (pH1.2) and simulated small intestine fluid (pH6.8). A high amount of 84.7% sustained release from NPs in simulated colonic fluid (pH7.4) was beyond 24 h. DiR-loaded NPs demonstrated a much higher colon accumulation, suggesting effective targeting due to functionalization with pH and time-dependent polymers. DFNPs could significantly ameliorate the colonic damage by reducing DAI, macroscopic score, histological damage and cell apoptosis. Our results also proved that the potent anti-inflammatory effect of DFNPs is contributed by decrease of NADPH, gene expression of COX-2 and MMP-9 and the production of TNF-α, IL-17, IL-23 and PGE2. Conclusion: We confirm that DFNPs exert protective effects through inhibiting the inflammatory response, which could be developed as a potential colon-targeted system.


Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Colon/patología , Glicósidos Iridoides/uso terapéutico , Nanopartículas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Ácidos Polimetacrílicos/química , Animales , Apoptosis/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/genética , Colitis Ulcerosa/patología , Colon/efectos de los fármacos , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Sulfato de Dextran , Liberación de Fármacos , Fluorescencia , Concentración de Iones de Hidrógeno , Glicósidos Iridoides/sangre , Glicósidos Iridoides/farmacocinética , Glicósidos Iridoides/farmacología , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos ICR , NADPH Oxidasas/metabolismo , Nanopartículas/ultraestructura , Tamaño de la Partícula , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Distribución Tisular/efectos de los fármacos
5.
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
6.
Int J Nanomedicine ; 16: 1819-1836, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33707942

RESUMEN

Background: The development of vaccines is a promising and cost-effective strategy to prevent emerging multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. The purpose of this study was to prepare a multiepitope peptide nanovaccine and evaluate its immunogenicity and protective effect in BALB/c mice. Methods: The B-cell and T-cell epitopes of Omp22 from A. baumannii were predicted using bioinformatics methods and identified by immunological experiments. The optimal epitopes were conjugated in series by 6-aminocaproic acid and chemically synthesized multiepitope polypeptide rOmp22. Then, rOmp22 was encapsulated by chitosan (CS) and poly (lactic-co-glycolic) acid (PLGA) to prepare CS-PLGA-rOmp22 nanoparticles (NPs). The immunogenicity and immunoprotective efficacy of the vaccine were evaluated in BALB/c mice. Results: CS-PLGA-rOmp22 NPs were small (mean size of 272.83 nm) with apparently spherical structures, positively charged (4.39 mV) and nontoxic to A549 cells. A high encapsulation efficiency (54.94%) and a continuous slow release pattern were achieved. Compared with nonencapsulated rOmp22, CS-PLGA-rOmp22 immunized BALB/c mice induced higher levels of rOmp22-specific IgG in serum and IFN-γ in splenocyte supernatant. Additionally, lung injury and bacterial burdens in the lung and blood were suppressed, and potent protection (57.14%-83.3%) against acute lethal intratracheal A. baumannii challenge was observed in BALB/c mice vaccinated with CS-PLGA-rOmp22. Conclusion: CS-PLGA-rOmp22 NPs elicited specific IgG antibodies, Th1 cellular immunity and protection against acute lethal intratracheal A. baumannii challenge. Our results indicate that this nanovaccine is a desirable candidate for preventing A. baumannii infection.


Asunto(s)
Infecciones por Acinetobacter/inmunología , Acinetobacter baumannii/inmunología , Vacunas Bacterianas/inmunología , Quitosano/química , Epítopos/inmunología , Nanopartículas/química , Péptidos/inmunología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Células A549 , Infecciones por Acinetobacter/sangre , Infecciones por Acinetobacter/microbiología , Secuencia de Aminoácidos , Animales , Anticuerpos Antibacterianos/inmunología , Carga Bacteriana , Peso Corporal , Epítopos/química , Femenino , Humanos , Inmunidad Humoral , Inmunización , Inmunoglobulina G/inmunología , Interferón gamma/metabolismo , Interleucina-4/metabolismo , Pulmón/inmunología , Pulmón/microbiología , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Nanopartículas/ultraestructura , Péptidos/química , Proteínas Recombinantes/aislamiento & purificación , Bazo/patología , Análisis de Supervivencia
7.
Nat Commun ; 12(1): 1689, 2021 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-33727548

RESUMEN

Administration of drugs via the buccal route has attracted much attention in recent years. However, developing systems with satisfactory adhesion under wet conditions and adequate drug bioavailability still remains a challenge. Here, we propose a mussel-inspired mucoadhesive film. Ex vivo models show that this film can achieve strong adhesion to wet buccal tissues (up to 38.72 ± 10.94 kPa). We also demonstrate that the adhesion mechanism of this film relies on both physical association and covalent bonding between the film and mucus. Additionally, the film with incorporated polydopamine nanoparticles shows superior advantages for transport across the mucosal barrier, with improved drug bioavailability (~3.5-fold greater than observed with oral delivery) and therapeutic efficacy in oral mucositis models (~6.0-fold improvement in wound closure at day 5 compared with that observed with no treatment). We anticipate that this platform might aid the development of tissue adhesives and inspire the design of nanoparticle-based buccal delivery systems.


Asunto(s)
Biomimética , Bivalvos/química , Sistemas de Liberación de Medicamentos , Mucosa Bucal/fisiología , Adhesividad , Administración Bucal , Animales , Línea Celular , Dexametasona/farmacología , Dihidroxifenilalanina/química , Liberación de Fármacos , Humanos , Indoles/toxicidad , Masculino , Mucinas/química , Moco/química , Nanopartículas/química , Nanopartículas/ultraestructura , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/toxicidad , Polímeros/toxicidad , Alcohol Polivinílico/química , Alcohol Polivinílico/toxicidad , Ratas Sprague-Dawley , Espectrofotometría Ultravioleta , Porcinos , Distribución Tisular
8.
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
9.
Carbohydr Polym ; 260: 117780, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33712136

RESUMEN

In this study, we prepared a biomimetic hyaluronic acid oligosaccharides (oHAs)-based composite scaffold to develop a bone tissue-engineered scaffold for stimulating osteogenesis and endothelialization. The functional oHAs products were firstly synthesized, namely collagen/hyaluronic acid oligosaccharides/hydroxyapatite (Col/oHAs/HAP), chitosan/hyaluronic acid oligosaccharides (CTS/oHAs), and then uniformly distributed in poly (lactic-co-glycolic acid) (PLGA) solution followed by freeze-drying to obtain three-dimensional interconnected scaffolds as temporary templates for bone regeneration. The morphology, physicochemical properties, compressive strength, and degradation behavior of the fabricated scaffolds, as well as in vitro cell responses seeded on these scaffolds and in vivo biocompatibility, were investigated to evaluate the potential for bone tissue engineering. The results indicated that the oHAs-based scaffolds can promote the attachment of endothelial cells, facilitate the osteogenic differentiation of MC3T3-E1 and BMSCs, and have ideal biocompatibility and tissue regenerative capacity, suggesting their potential to serve as alternative candidates for bone tissue engineering applications.


Asunto(s)
Materiales Biocompatibles/química , Quitosano/química , Colágeno/química , Ingeniería de Tejidos , Animales , Materiales Biocompatibles/farmacología , Diferenciación Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Durapatita/química , Ácido Hialurónico/química , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones , Oligosacáridos/química , Osteoblastos/citología , Osteoblastos/metabolismo , Osteogénesis/efectos de los fármacos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Andamios del Tejido/química
10.
Int J Nanomedicine ; 16: 1189-1206, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33623382

RESUMEN

Introduction: Human immunodeficiency virus (HIV) remains a persistent global challenge, impacting 38 million people worldwide. Antiretrovirals (ARVs) including tenofovir (TFV), raltegravir (RAL), and dapivirine (DAP) have been developed to prevent and treat HIV-1 via different mechanisms of action. In parallel, a promising biological candidate, griffithsin (GRFT), has demonstrated outstanding preclinical safety and potency against HIV-1. While ARV co-administration has been shown to enhance virus inhibition, synergistic interactions between ARVs and the oxidation-resistant variant of GRFT (Q-GRFT) have not yet been explored. Here, we co-administered Q-GRFT with TFV, RAL, and DAP, in free and encapsulated forms, to identify unique protein-drug synergies. Methods: Nanoparticles (NPs) were synthesized using a single or double-emulsion technique and release from each formulation was assessed in simulated vaginal fluid. Next, each ARV, in free and encapsulated forms, was co-administered with Q-GRFT or Q-GRFT NPs to evaluate the impact of co-administration in HIV-1 pseudovirus assays, and the combination indices were calculated to identify synergistic interactions. Using the most synergistic formulations, we investigated the effect of agent incorporation in NP-fiber composites on release properties. Finally, NP safety was assessed in vitro using MTT assay. Results: All active agents were encapsulated in NPs with desirable encapsulation efficiency (15-100%), providing ~20% release over 2 weeks. The co-administration of free Q-GRFT with each free ARV resulted in strong synergistic interactions, relative to each agent alone. Similarly, Q-GRFT NP and ARV NP co-administration resulted in synergy across all formulations, with the most potent interactions between encapsulated Q-GRFT and DAP. Furthermore, the incorporation of Q-GRFT and DAP in NP-fiber composites resulted in burst release of DAP and Q-GRFT with a second phase of Q-GRFT release. Finally, all NP formulations exhibited safety in vitro. Conclusions: This work suggests that Q-GRFT and ARV co-administration in free or encapsulated forms may improve efficacy in achieving prophylaxis.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Lectinas/uso terapéutico , Fármacos Anti-VIH/farmacología , Antirretrovirales/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular , Composición de Medicamentos , Liberación de Fármacos , Sinergismo Farmacológico , Femenino , VIH-1/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Lectinas/farmacología , Nanopartículas/química , Nanopartículas/ultraestructura , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Pirimidinas/farmacología , Raltegravir Potásico/farmacología , Tenofovir/farmacología
11.
Int J Nanomedicine ; 16: 951-976, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33603362

RESUMEN

Purpose: Lipoparticles are the core-shell type lipid-polymer hybrid systems comprising polymeric nanoparticle core enveloped by single or multiple pegylated lipid layers (shell), thereby melding the biomimetic properties of long-circulating vesicles as well as the mechanical advantages of the nanoparticles. The present study was aimed at the development of such an integrated system, combining the photodynamic and chemotherapeutic approaches for the treatment of multidrug-resistant cancers. Methods: For this rationale, two different sized Pirarubicin (THP) loaded poly lactic-co-glycolic acid (PLGA) nanoparticles were prepared by emulsion solvent evaporation technique, whereas liposomes containing Temoporfin (mTHPC) were prepared by lipid film hydration method. Physicochemical and morphological characterizations were done using dynamic light scattering, laser doppler anemometry, atomic force microscopy, and transmission electron microscopy. The quantitative assessment of cell damage was determined using MTT and reactive oxygen species (ROS) assay. The biocompatibility of the nanoformulations was evaluated with serum stability testing, haemocompatibility as well as acute in vivo toxicity using female albino (BALB/c) mice. Results and Conclusion: The mean hydrodynamic diameter of the formulations was found between 108.80 ± 2.10 to 405.70 ± 10.00 nm with the zeta (ζ) potential ranging from -12.70 ± 1.20 to 5.90 ± 1.10 mV. Based on the physicochemical evaluations, the selected THP nanoparticles were coated with mTHPC liposomes to produce lipid-coated nanoparticles (LCNPs). A significant (p< 0.001) cytotoxicity synergism was evident in LCNPs when irradiated at 652 nm, using an LED device. No incidence of genotoxicity was observed as seen with the comet assay. The LCNPs decreased the generalized in vivo toxicity as compared to the free drugs and was evident from the serum biochemical profile, visceral body index, liver function tests as well as renal function tests. The histopathological examinations of the vital organs revealed no significant evidence of toxicity suggesting the safety and efficacy of our lipid-polymer hybrid system.


Asunto(s)
Lípidos/química , Nanopartículas/química , Neoplasias Ováricas/tratamiento farmacológico , Fotoquimioterapia , Animales , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Liberación de Fármacos , Femenino , Humanos , Concentración 50 Inhibidora , Cinética , Liposomas , Pruebas de Función Hepática , Mesoporfirinas/farmacología , Mesoporfirinas/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Nanopartículas/ultraestructura , Neoplasias Ováricas/patología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Especies Reactivas de Oxígeno/metabolismo , Pruebas de Toxicidad Aguda
12.
ACS Appl Mater Interfaces ; 13(7): 7913-7923, 2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33573372

RESUMEN

Biomimetic biomaterials are being actively explored in the context of cancer immunotherapy because of their ability to directly engage the immune system to generate antitumor responses. Unlike cellular therapies, biomaterial-based immunotherapies can be precisely engineered to exhibit defined characteristics including biodegradability, physical size, and tuned surface presentation of immunomodulatory signals. In particular, modulating the interface between the biomaterial surface and the target biological cell is key to enabling biological functions. Synthetic artificial antigen presenting cells (aAPCs) are promising as a cancer immunotherapy but are limited in clinical translation by the requirement of ex vivo cell manipulation and adoptive transfer of antigen-specific CD8+ T cells. To move toward acellular aAPC technology for in vivo use, we combine poly(lactic-co-glycolic acid) (PLGA) and cationic poly(beta-amino-ester) (PBAE) to form a biodegradable blend based on the hypothesis that therapeutic aAPCs fabricated from a cationic blend may have improved functions. PLGA/PBAE aAPCs demonstrate enhanced surface interactions with antigen-specific CD8+ T cells that increase T cell activation and expansion ex vivo, associated with significantly increased conjugation efficiency of T cell stimulatory signals to the aAPCs. Critically, these PLGA/PBAE aAPCs also expand antigen-specific cytotoxic CD8+ T cells in vivo without the need of adoptive transfer. Treatment with PLGA/PBAE aAPCs in combination with checkpoint therapy decreases tumor growth and extends survival in a B16-F10 melanoma mouse model. These results demonstrate the potential of PLGA/PBAE aAPCs as a biocompatible, directly injectable acellular therapy for cancer immunotherapy.


Asunto(s)
Células Presentadoras de Antígenos/inmunología , Células Artificiales/inmunología , Inmunoterapia , Melanoma/terapia , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/inmunología , Polímeros/química , Animales , Células Artificiales/química , Linfocitos T CD8-positivos/inmunología , Cationes/química , Cationes/inmunología , Melanoma/inmunología , Ratones , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Propiedades de Superficie
13.
Arch Oral Biol ; 123: 105041, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33454420

RESUMEN

OBJECTIVE: The aim of this study was to develop a composite scaffold with the optimal poly(lactic-co-glycolic acid) (PLGA) and bioactive glass proportions to provide an environment for bone tissue regeneration and repair. DESIGN: PLGA-bioactive glass composite scaffolds were prepared using a salt-leaching technique with different percentages of bioactive glass (0%, 10 %, and 15 % [w/w]) with PLGA. The resulting scaffolds were characterized using scanning electron microscopy and energy dispersive X-ray spectroscopy (SEM-EDS), and water contact angle, dynamic mechanical, and pH analysis. The scaffold biocompatibility was investigated using stem cells from human exfoliated deciduous teeth (SHED) and rat experiments. RESULTS: SEM-EDS confirmed the successful fabrication of three-dimensional PLGA-bioactive glass scaffolds. The results showed that 10 % bioactive glass with PLGA exhibited favorable properties including increased pore size, hydrophilicity, and mechanical properties. The growth medium pH was increased for scaffolds containing bioactive glass. All scaffolds were biocompatible, and 10 % bioactive glass composite scaffolding showed better attachment, growth, and proliferation of SHED compared to the other scaffolds. Moreover, it enhanced osteogenic differentiation of SHED in vitro and in vivo. CONCLUSIONS: Salt-leaching-derived PLGA-bioactive glass composite scaffolds were successfully established. PLGA with 10 % bioactive glass had adequate physical properties and bioactivity, and it could be considered as a composite for bone tissue engineering applications.


Asunto(s)
Vidrio/química , Osteogénesis , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Células Madre/citología , Ingeniería de Tejidos , Andamios del Tejido , Animales , Humanos , Porosidad , Ratas , Diente Primario/citología
14.
ACS Appl Mater Interfaces ; 13(5): 5975-5988, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33502166

RESUMEN

The structural layers around oocytes make it difficult to deliver drugs aimed at treating infertility. In this study, we sought to identify nanoparticles (NPs) that could easily pass through zona pellucida (ZP), a special layer around oocytes, for use as a drug delivery carrier. Three types of NPs were tested: quantum dot NPs, PE-polyethylene glycol (PEG)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs (PEG/PL), and tetramethylrhodamine-loaded PLGA NPs (TRNPs). When mouse oocytes were treated with NPs, only TRNPs could fully pass through the ZP and cell membrane. To assess the effects of TRNPs on fertility and potential nanotoxicity, we performed mRNA sequencing analysis to confirm their genetic safety. We established a system to successfully internalize TRNPs into oocytes. The genetic stability and normal development of TRNP-treated oocytes and embryos were confirmed. These results imply that TRNPs can be used as a drug delivery carrier applicable to germ cells.


Asunto(s)
Sistemas de Liberación de Medicamentos , Nanopartículas/química , Oocitos/efectos de los fármacos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Rodaminas/química , Animales , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Femenino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Estructura Molecular , Tamaño de la Partícula , Polietilenglicoles/química , Rodaminas/farmacología , Propiedades de Superficie
15.
AAPS PharmSciTech ; 22(1): 35, 2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33404988

RESUMEN

Non-infectious uveitis, an ocular inflammatory condition that affects the iris, ciliary body, choroid, and adjacent tissues (retina, optic nerve, and vitreous), is an important cause of blindness worldwide. Sirolimus (SRL), a potent immunomodulatory drug, has shown promising results in the treatment of inflammatory ocular diseases. Despite this therapeutic potential, its clinical use is a major challenge due to low bioavailability and poor solubility. Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable polymer commonly used for ophthalmic drug delivery due to its suitable characteristics such as biocompatibility, good mechanical properties, and improvement of the pharmacokinetic profile of the drug. In the present study, we investigated the effects of SRL-PLGA implant on experimental autoimmune uveitis in rabbits. Clinical and histopathological examinations were performed, followed by assessment of protein levels and determination of myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activity in the aqueous humor/vitreous. As a result, treated eyes had decreased average inflammatory scores, protein significant decreases in treated eyes, assessed after 35 days. Histopathological examination showed less severe intraocular inflammation and decreased tissue damage in treated eyes. According to these results, the SRL-PLGA implant evaluated in this study was apparently safe, reducing inflammation in treated eyes, with an extended effect possibly associated with prolonged release of SRL in the posterior segment of the eye. Therefore, intravitreal SRL-PLGA implant could be a promising alternative for treatment of non-infectious uveitis.


Asunto(s)
Implantes de Medicamentos , Inmunosupresores/administración & dosificación , Sirolimus/administración & dosificación , Uveítis/tratamiento farmacológico , Cuerpo Vítreo , Animales , Inmunosupresores/uso terapéutico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Conejos , Sirolimus/uso terapéutico , Solubilidad
16.
ACS Appl Mater Interfaces ; 13(3): 4567-4573, 2021 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-33442976

RESUMEN

A film with an elaborate microstructure and multifunctions is urgently needed in wound healing. Here, we present a multiactive encapsulated inverse opal film with a monitorable delivery system for chronic wound healing. The inverse opal film is prepared by using poly(lactic-co-glycolic acid) to negatively replicate a colloidal crystal template, which presents a high specific surface area and interconnected nanopores. It could be imparted with a potent antibacterial effect and promote angiogenesis by loading the vascular endothelial growth factor into the nanopores and encapsulating by chitosan. In addition, it is demonstrated that the structure color change of the film could intuitively reflect the drug release progress from the nanopores, which made the film a real-time drug monitoring system. In the affected wound model, the properties of the multifunctional film in promoting wound healing are certified by the faster healing speed, more granulation tissue, less inflammation, and even a distribution of new blood vessels and collagen. These results indicate that the resultant multifunctional film has a practical application value in clinical wound care.


Asunto(s)
Antibacterianos/administración & dosificación , Sistemas de Liberación de Medicamentos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Factor A de Crecimiento Endotelial Vascular/administración & dosificación , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Materiales Biocompatibles/química , Quitosano/química , Coloides/química , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Ratones , Células 3T3 NIH , Porosidad , Ratas , Factor A de Crecimiento Endotelial Vascular/farmacología , Factor A de Crecimiento Endotelial Vascular/uso terapéutico
17.
ACS Appl Mater Interfaces ; 13(3): 3605-3621, 2021 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-33449625

RESUMEN

Breast cancer is a major threat to health and lives of females. Biomimetic nanotechnology brought brighter hope for early diagnosis and treatment of breast cancer. Here, we proposed a platelet (PLT) membrane-derived strategy for enhanced photoacoustic (PA)/ultrasonic (US)/fluorescence (FL) multimodal imaging and augmented synergistic photothermal/chemotherapeutic efficacy in tumor cells. A PA imaging contrast and photothermal agent, nanocarbons (CNs), a chemotherapeutic and FL material, doxorubicin (DOX), and perfluoropentane (PFP) were coencapsulated into the poly(lactic-co-glycolic) acid (PLGA) skeletons. Then, the PLT membranes were coated onto the PLGA NPs, which were named as "nanoplatelets" (DOX-PFP-CNs@PLGA/PM NPs). The "nanoplatelets", which conserved the structural advantages and inherent properties of PLTs, could not only escape from phagocytosis of macrophages but also actively targeted tumor cells by the way of antigen-antibody interactions between P-selectin on the PM and CD44 receptors of the tumor cells. With CNs and DOX loaded in, these "nanoplatelets" could serve as an excellent contrast agent for PA/FL imaging. Under laser irradiation, the "nanoplatelets" could turn light energy into heat energy. The laser-triggered photothermal effect, on the one hand, could ablate the tumor cells immediately, and on the other hand, could initiate the optical droplet vaporization of PFP, which subsequently enhanced US imaging and promoted the discharge of encapsulated DOX from the "nanoplatelets" for remarkably strengthening photothermal therapeutic power in turn. In this work, as compared with the bare drug-loaded nanoparticles, the "nanoplatelets" exhibited much more accumulation in the tumor cells, demonstrating superior multimodal imaging capability and preferable synergistic therapeutic performance. In conclusion, the "nanoplatelets" could serve as contrast agents for US imaging and PA imaging to guide the therapy. What is more, the bioinspired PLT-derived, targeted, and nontoxic "nanoplatelets", which were exploited for multimodal PA/US/FL imaging-guided synergistic photothermal/chemo therapy, will be of great value to breast cancer theranostics in the days to come.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/terapia , Sistemas de Liberación de Medicamentos/métodos , Nanoestructuras/química , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/uso terapéutico , Materiales Biomiméticos/química , Biomimética , Neoplasias de la Mama/patología , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Femenino , Fluorocarburos/administración & dosificación , Fluorocarburos/uso terapéutico , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratones , Ratones Endogámicos BALB C , Imagen Óptica/métodos , Técnicas Fotoacústicas/métodos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Nanomedicina Teranóstica/métodos
18.
Food Chem ; 346: 128742, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33373823

RESUMEN

The use of poly-ß-hydroxybutyrate (PHB) is an alternative polymer that can be considered environment friendly and renewable to prepare nanoparticles of carotenoids. This study aimed to develop and characterize aqueous dispersion nanoparticles and lyophilized nanoparticles of carotenoid extract obtained from Spirulina sp. LEB 18 by nanoprecipitation, using poly d,l-lactic acid (PLA)/poly d,l-lactic-co-glycolic acid (PLGA) (75:25 w/w) or PHB as encapsulants. The samples were characterized for the particle size, polydispersity index, zeta potential, apparent viscosity, pH, color parameters, ultraviolet-visible (UV/Vis) spectrophotometry, carotenoid profile, encapsulation efficiency, morphology, and thermal analysis. Nanoparticles containing microalgae carotenoid extract showed average particle diameter on a nanoscale (<200 nm), high homogeneity and stability, high thermal stability, and encapsulation efficiency carotenoid (>80%) when compared to nanoparticles containing ß-carotene synthetic. PHB or PLA/PLGA as encapsulating material in the production of nanoparticles from microalgae carotenoids can be a polymeric alternative capable of promoting greater stability and application of carotenoids.


Asunto(s)
Carotenoides/farmacología , Hidroxibutiratos/química , Nanopartículas/química , Poliésteres/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Spirulina/química , beta Caroteno/química , Carotenoides/aislamiento & purificación , Portadores de Fármacos/química , Excipientes , Tamaño de la Partícula
19.
Methods Mol Biol ; 2174: 263-275, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32813256

RESUMEN

In recent decades, zebrafish (Danio rerio) has become a major in vivo model for the evaluation of drug efficacies and toxicities. In the field of drug delivery research, zebrafish larvae are a suitable model for the use of fluorescent-labeled chemicals, nanoparticle, liposome, or micelle-mediated delivery systems because of their transparent body wall. In the current chapter, we describe the method to perform micelle-based siRNA delivery using cancer cells implanted into the circulation of zebrafish.


Asunto(s)
Técnicas de Transferencia de Gen , ARN Interferente Pequeño/farmacología , Pez Cebra , Animales , Animales Modificados Genéticamente , Carbocianinas/química , Línea Celular Tumoral , Trasplante de Células , Sistemas de Liberación de Medicamentos/métodos , Colorantes Fluorescentes/química , Humanos , Larva/genética , Proteínas Luminiscentes/genética , Melanoma/patología , Micelas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , ARN Interferente Pequeño/química , ARN Interferente Pequeño/genética , Trasplantes , Pez Cebra/genética
20.
Nanoscale ; 13(1): 388-396, 2021 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-33351018

RESUMEN

Inspired by the self-assembly approach, in this work, the chromogen, 3,3',5,5'-tetramethylbenzidine (TMB), was successfully co-precipitated in aqueous solution to form collective nanoparticles (NPs) of signal molecules (TMB-NPs). Utilizing poly(lactide-co-glycolide) (PLGA) in the molecular delivery approach, the formed emulsion nanovesicle (TMB-NPs@PLGA) exhibits an enrichment of the collective signal molecules in a single antibody-antigen conjugation. A specific antibody-conjugated TMB-NPs@PLGA forms an immunocomplex sandwich structure upon the addition of influenza virus (IV)/A. The addition of dimethyl sulfoxide (DMSO) dissolves the PLGA nanovesicles, releasing the encapsulated TMB-NPs. Sequentially, the TMB-NPs release TMB molecules upon the addition of DMSO. The released TMB is catalytically oxidized by H2O2 with self-assembled protein-inorganic nanoflowers, where copper nanoflowers (CuNFs) acted as the nanozyme. The developed immunoassay demonstrates high sensitivity for IV/A with a limit of detection (LOD) as low as 32.37 fg mL-1 and 54.97 fg mL-1 in buffer and serum, respectively. For practical needs, a clinically isolated IV/A/H3N2 and spike protein of SARS-CoV-2 were detected with the LODs of 17 pfu mL-1 and 143 fg mL-1, respectively. These results show the applicability of the advanced TMB-NPs@PLGA-based colorimetric sensor for the highly sensitive detection of airborne respiratory viruses.


Asunto(s)
Técnicas Biosensibles/métodos , Compuestos Cromogénicos/química , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Infecciones del Sistema Respiratorio , /aislamiento & purificación , Bencidinas/química , /virología , Humanos , Peróxido de Hidrógeno , Inmunoensayo/métodos , Gripe Humana/diagnóstico , Gripe Humana/virología , Límite de Detección , Nanopartículas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/virología , Glicoproteína de la Espiga del Coronavirus
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...