Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.263
Filtrar
1.
Nat Commun ; 12(1): 4883, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385449

RESUMO

Pure organic room-temperature phosphorescent (RTP) materials have been suggested to be promising bioimaging materials due to their good biocompatibility and long emission lifetime. Herein, we report a class of RTP materials. These materials are developed through the simple introduction of an aromatic carbonyl to a tetraphenylpyrrole molecule and also exhibit aggregation-induced emission (AIE) properties. These molecules show non-emission in solution and purely phosphorescent emission in the aggregated state, which are desirable properties for biological imaging. Highly crystalline nanoparticles can be easily fabricated with a long emission lifetime (20 µs), which eliminate background fluorescence interference from cells and tissues. The prepared nanoparticles demonstrate two-photon absorption characteristics and can be excited by near infrared (NIR) light, making them promising materials for deep-tissue optical imaging. This integrated aggregation-induced phosphorescence (AIP) strategy diversifies the existing pool of bioimaging agents to inspire the development of bioprobes in the future.


Assuntos
Corantes Fluorescentes/química , Luminescência , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Nanopartículas/química , Pirróis/química , Imagem com Lapso de Tempo/métodos , Animais , Células HeLa , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Confocal/métodos , Microscopia Eletrônica de Transmissão/métodos , Nanopartículas/ultraestrutura , Tamanho da Partícula
2.
Commun Biol ; 4(1): 956, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381159

RESUMO

Lipid Nanoparticles (LNPs) are used to deliver siRNA and COVID-19 mRNA vaccines. The main factor known to determine their delivery efficiency is the pKa of the LNP containing an ionizable lipid. Herein, we report a method that can predict the LNP pKa from the structure of the ionizable lipid. We used theoretical, NMR, fluorescent-dye binding, and electrophoretic mobility methods to comprehensively measure protonation of both the ionizable lipid and the formulated LNP. The pKa of the ionizable lipid was 2-3 units higher than the pKa of the LNP primarily due to proton solvation energy differences between the LNP and aqueous medium. We exploited these results to explain a wide range of delivery efficiencies in vitro and in vivo for intramuscular (IM) and intravascular (IV) administration of different ionizable lipids at escalating ionizable lipid-to-mRNA ratios in the LNP. In addition, we determined that more negatively charged LNPs exhibit higher off-target systemic expression of mRNA in the liver following IM administration. This undesirable systemic off-target expression of mRNA-LNP vaccines could be minimized through appropriate design of the ionizable lipid and LNP.


Assuntos
Expressão Gênica , Íons/química , Lipídeos/química , Nanopartículas/química , RNA Mensageiro/química , RNA Mensageiro/genética , Administração Intravenosa , Animais , Composição de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Injeções Intramusculares , Camundongos , Estrutura Molecular , Nanopartículas/ultraestrutura , RNA Mensageiro/administração & dosagem , RNA Mensageiro/farmacocinética , Análise Espectral , Distribuição Tecidual , Transfecção
3.
Int J Nanomedicine ; 16: 4631-4642, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262273

RESUMO

Purpose: Antibiotic-resistant bacteria are pathogens that have emerged as a serious public health risk. Thus, there is an urgent need to develop a new generation of anti-bacterial materials to kill antibiotic-resistant bacteria. Methods: Nanosilver-decorated mesoporous organosilica nanoparticles (Ag-MONs) were fabricated for co-delivery of gentamicin (GEN) and nanosilver. After investigating the glutathione (GSH)-responsive matrix degradation and controlled release of both GEN and silver ions, the anti-bacterial activities of Ag-MONs@GEN were systematically determined against several antibiotic-susceptible and antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Furthermore, the cytotoxic profiles of Ag-MONs@GEN were evaluated. Results: The GEN-loaded nanoplatform (Ag-MONs@GEN) showed glutathione-responsive matrix degradation, resulting in the simultaneous controlled release of GEN and silver ions. Ag-MONs@GEN exhibited excellent anti-bacterial activities than Ag-MONs and GEN alone via inducing ROS generation, especially enhancing synergetic effects against four antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Moreover, the IC50 values of Ag-MONs@GEN in L929 and HUVECs cells were 313.6 ± 15.9 and 295.7 ± 12.3 µg/mL, respectively, which were much higher than their corresponding minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Conclusion: Our study advanced the development of Ag-MONs@GEN for the synergistic and safe treatment of antibiotic-resistant bacteria.


Assuntos
Resistência Microbiana a Medicamentos/efeitos dos fármacos , Gentamicinas/farmacologia , Glutationa/química , Nanopartículas/química , Dióxido de Silício/química , Prata/química , Animais , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Nanopartículas/ultraestrutura
4.
Int J Nanomedicine ; 16: 4677-4691, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262275

RESUMO

Background: The clinical use of therapeutic peptides has been limited because of their inefficient delivery approaches and, therefore, inadequate delivery to target sites. Buccal administration of therapeutic peptides offers patients a potential alternative to the current invasive routes of administration. Purpose: The aim of the study was to fabricate hydrophobic ion-pairing (HIP)-nanocomplexes (C1 and C2) utilizing anionic bile salts and cationic peptides, and to assess their permeability across TR146 buccal cell layers and porcine buccal tissue. Methods: C1 and C2-nanocomplexes were fabricated using the HIP approach. In addition, their physiochemical and morphological attributes, in vitro and ex vivo permeability properties, and qualitative and quantitative cellular uptake were evaluated and compared. The localization of C1 and C2-nanocomplexes in porcine buccal tissue was determined using confocal laser scanning microscopy. Results: The C1-nanocomplex was the superior nanocarrier and significantly enhanced the transport of insulin across TR146 cell layers and porcine buccal tissue, exhibiting a 3.00- and 51.76-fold increase in permeability coefficient, respectively, when compared with insulin solution (p < 0.01). C1-nanocomplex was more efficient than C2-nanocomplex at facilitating insulin permeability, with a 2.18- and 27.64-fold increase across TR146 cell layers and porcine buccal tissue, respectively. The C1-nanocomplex demonstrated immense uptake and localization of insulin in TR146 cells and porcine buccal tissue, as evidenced by a highly intense fluorescence in TR146 cells, and a great shift of fluorescence intensity towards the inner region of buccal tissue over time. The increase in fluorescence intensity was observed in the order of C1 > C2 > insulin solution. Conclusion: In this study, we highlighted the efficacy of potential nanocarriers in addressing the daunting issues associated with the invasive administration of insulin and indicated a promising strategy for the buccal administration and delivery of this life-saving peptide hormone.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Insulina/administração & dosagem , Insulina/farmacologia , Mucosa Bucal/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Endocitose/efeitos dos fármacos , Humanos , Íons , Nanopartículas/química , Nanopartículas/ultraestrutura , Suínos
5.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34204001

RESUMO

Radiodynamic therapy (RDT) is a recent extension of conventional photodynamic therapy, in which visible/near infrared light irradiation is replaced by a well-tolerated dose of high-energy X-rays. This enables greater tissue penetration to allow non-invasive treatment of large, deep-seated tumors. We report here the design and testing of a drug delivery system for RDT that is intended to enhance intra- or peri-nuclear localization of the photosensitizer, leading to DNA damage and resulting clonogenic cell kill. This comprises a photosensitizer (Verteporfin, VP) incorporated into poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) that are surface-functionalized with a cell-penetrating HIV trans-activator of transcription (TAT) peptide. In addition to a series of physical and photophysical characterization studies, cytotoxicity tests in pancreatic (PANC-1) cancer cells in vitro under 4 Gy X-ray exposure from a clinical 6 MV linear accelerator (LINAC) showed that TAT targeting of the nanoparticles markedly enhances the effectiveness of RDT treatment, particularly when assessed by a clonogenic, i.e., DNA damage-mediated, cell kill.


Assuntos
Composição de Medicamentos , Produtos do Gene tat/química , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Verteporfina/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Clonais , DNA/metabolismo , Endocitose/efeitos dos fármacos , Humanos , Lipídeos de Membrana/metabolismo , Nanopartículas/ultraestrutura , Oxigênio Singlete/metabolismo
6.
Nat Commun ; 12(1): 4556, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315880

RESUMO

The potential applications of covalent organic frameworks (COFs) can be further developed by encapsulating functional nanoparticles within the frameworks. However, the synthesis of monodispersed core@shell structured COF nanocomposites without agglomeration remains a significant challenge. Herein, we present a versatile dual-ligand assistant strategy for interfacial growth of COFs on the functional nanoparticles with abundant physicochemical properties. Regardless of the composition, geometry or surface properties of the core, the obtained core@shell structured nanocomposites with controllable shell-thickness are very uniform without agglomeration. The derived bowl-shape, yolk@shell, core@satellites@shell nanostructures can also be fabricated delicately. As a promising type of photosensitizer for photodynamic therapy (PDT), the porphyrin-based COFs were grown onto upconversion nanoparticles (UCNPs). With the assistance of the near-infrared (NIR) to visible optical property of UCNPs core and the intrinsic porosity of COF shell, the core@shell nanocomposites can be applied as a nanoplatform for NIR-activated PDT with deep tissue penetration and chemotherapeutic drug delivery.


Assuntos
Estruturas Metalorgânicas/química , Nanopartículas/química , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Ligantes , Camundongos Endogâmicos BALB C , Nanocompostos/química , Nanopartículas/ultraestrutura , Fotoquimioterapia , Porfirinas/química , Dióxido de Silício/química , Tela Subcutânea/efeitos dos fármacos , Tela Subcutânea/patologia
7.
Int J Mol Sci ; 22(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299308

RESUMO

In bone surgery and orthopedics, bioresorbable materials can be helpful in bone repair and countering post-op infections. Explicit antibacterial activity, osteoinductive and osteoconductive effects are essential to achieving this objective. Nonwoven electrospun (ES) fibers are receiving the close attention of physicians as promising materials for wound dressing and tissue engineering; potentially, in high contrast with dense materials, ES mats hamper regeneration of the bone extracellular matrix to a lesser extent. The use of the compositions of inherently biodegradable polyesters (poly(ε-caprolactone) PCL, poly(lactoglycolide), etc.), calcium phosphates and antibiotics is highly prospective, but the task of forming ES fibers from such compositions is complicated by the incompatibility of the main organic and inorganic ingredients, polyesters and calcium phosphates. In the present research we report the synthesis of hydroxyapatite (HAp) nanoparticles with uniform morphology, and demonstrate high efficiency of the block copolymer of PCL and poly(ethylene phosphoric acid) (PEPA) as an efficient compatibilizer for PCL/HAp mixtures that are able to form ES fibers with improved mechanical characteristics. The materials obtained in the presence of vancomycin exhibited incremental drug release against Staphylococcus aureus (St. aureus).


Assuntos
Antibacterianos/química , Substitutos Ósseos/química , Hidroxiapatitas/química , Antibacterianos/administração & dosagem , Fenômenos Biomecânicos , Liberação Controlada de Fármacos , Humanos , Técnicas In Vitro , Teste de Materiais , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanofibras/química , Nanofibras/ultraestrutura , Nanopartículas/química , Nanopartículas/ultraestrutura , Poliésteres/química , Polietilenos/química , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/administração & dosagem , Vancomicina/química , Difração de Raios X
8.
Commun Biol ; 4(1): 846, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267305

RESUMO

Dental plaques are biofilms that cause dental caries by demineralization with acidogenic bacteria. These bacteria reside inside a protective sheath which makes any curative treatment challenging. We propose an antibiotic-free strategy to disrupt the biofilm by engineered clustered carbon dot nanoparticles that function in the acidic environment of the biofilms. In vitro and ex vivo studies on the mature biofilms of Streptococcus mutans revealed >90% biofilm inhibition associated with the contact-mediated interaction of nanoparticles with the bacterial membrane, excessive reactive oxygen species generation, and DNA fragmentation. An in vivo examination showed that these nanoparticles could effectively suppress the growth of S. mutans. Importantly, 16S rRNA analysis of the dental microbiota showed that the diversity and richness of bacterial species did not substantially change with nanoparticle treatment. Overall, this study presents a safe and effective approach to decrease the dental biofilm formation without disrupting the ecological balance of the oral cavity.


Assuntos
Biofilmes/efeitos dos fármacos , Microbiota/fisiologia , Nanopartículas/toxicidade , Polímeros/toxicidade , Streptococcus mutans/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Biofilmes/crescimento & desenvolvimento , Feminino , Humanos , Camundongos , Viabilidade Microbiana/efeitos dos fármacos , Microbiota/genética , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Células NIH 3T3 , Nanopartículas/química , Nanopartículas/ultraestrutura , Polímeros/química , RNA Ribossômico 16S/genética , Ratos Sprague-Dawley , Streptococcus mutans/crescimento & desenvolvimento , Streptococcus mutans/ultraestrutura
9.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198522

RESUMO

We synthesized phenylboronic acid pinacol ester (PBPE)-conjugated hyaluronic acid (HA) via thiobis(ethylamine) (TbEA) linkage (abbreviated as HAsPBPE conjugates) to fabricate the radiosensitive delivery of caffeic acid phenetyl ester (CAPE) and for application in radioprotection. PBPE was primarily conjugated with TbEA and then PBPE-TbEA conjugates were conjugated again with hyaluronic acid using carbodiimide chemistry. CAPE-incorporated nanoparticles of HAsPBPE were fabricated by the nanoprecipitation method and then the organic solvent was removed by dialysis. CAPE-incorporated HAsPBPE nanoparticles have a small particle size of about 80 or 100 nm and they have a spherical shape. When CAPE-incorporated HAsPBPE nanoparticles were irradiated, nanoparticles became swelled or disintegrated and their morphologies were changed. Furthermore, the CAPE release rate from HAsPBPE nanoparticles were increased according to the radiation dose, indicating that CAPE-incorporated HAsPBPE nanoparticles have radio-sensitivity. CAPE and CAPE-incorporated HAsPBPE nanoparticles appropriately prevented radiation-induced cell death and suppressed intracellular accumulation of reactive oxygen species (ROS). CAPE and CAPE-incorporated HAsPBPE nanoparticles efficiently improved survivability of mice from radiation-induced death and reduced apoptotic cell death. We suggest that HAsPBPE nanoparticles are promising candidates for the radio-sensitive delivery of CAPE.


Assuntos
Ácidos Borônicos/química , Ácidos Cafeicos/farmacologia , Glicóis/química , Ácido Hialurônico/química , Nanopartículas/química , Álcool Feniletílico/análogos & derivados , Proteção Radiológica , Animais , Ácidos Borônicos/síntese química , Ácidos Cafeicos/síntese química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Peróxido de Hidrogênio/toxicidade , Fígado/metabolismo , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Tamanho da Partícula , Álcool Feniletílico/síntese química , Álcool Feniletílico/farmacologia , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier
10.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204217

RESUMO

In this paper, the study of surface modification of two-dimensional (2D), non-luminescent CdS nanoplates (NPLs) by thiol-containing ligands is presented. We show that a process of twophase transfers with appropriate ligand exchange transforms non-luminescent NPLs into spherical CdS nanoparticles (NPs) exhibiting a blue photoluminescence with exceptionally high quantum yield ~90%. In the process, transfer from inorganic solvent to water is performed, with appropriately selected ligand molecules and pH values (forward phase transfer), which produces NPs with modified size and shape. Then, in reverse phase transfer, NPs are transferred back to toluene due to surface modification by combined Cd (OL)2 and Cd (Ac)2. As a result, spherical NPs are formed (average diameter between 4 and 6 nm) with PL QY as high as 90%. This is unique for core only CdS NPs without inorganic shell.


Assuntos
Compostos de Cádmio/química , Nanopartículas/química , Pontos Quânticos/química , Sulfetos/química , Fenômenos Químicos , Técnicas de Química Sintética , Nanopartículas/ultraestrutura , Transição de Fase , Análise Espectral
11.
Theranostics ; 11(14): 7005-7017, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093867

RESUMO

The tumor suppressor protein p53 remains in a wild type but inactive form in ~50% of all human cancers. Thus, activating it becomes an attractive approach for targeted cancer therapies. In this regard, our lab has previously discovered a small molecule, Inauhzin (INZ), as a potent p53 activator with no genotoxicity. Method: To improve its efficacy and bioavailability, here we employed nanoparticle encapsulation, making INZ-C, an analog of INZ, to nanoparticle-encapsulated INZ-C (n-INZ-C). Results: This approach significantly improved p53 activation and inhibition of lung and colorectal cancer cell growth by n-INZ-C in vitro and in vivo while it displayed a minimal effect on normal human Wi38 and mouse MEF cells. The improved activity was further corroborated with the enhanced cellular uptake observed in cancer cells and minimal cellular uptake observed in normal cells. In vivo pharmacokinetic evaluation of these nanoparticles showed that the nanoparticle encapsulation prolongates the half-life of INZ-C from 2.5 h to 5 h in mice. Conclusions: These results demonstrate that we have established a nanoparticle system that could enhance the bioavailability and efficacy of INZ-C as a potential anti-cancer therapeutic.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Indóis/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Fenotiazinas/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Disponibilidade Biológica , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Indóis/química , Indóis/farmacocinética , Indóis/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Fenotiazinas/química , Fenotiazinas/farmacocinética , Fenotiazinas/uso terapêutico , Espectroscopia de Infravermelho com Transformada de Fourier , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Theranostics ; 11(14): 7045-7056, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093870

RESUMO

Rationale: Precise treatment of tumors is attracting increasing attention. Molecular probes simultaneously demonstrating the diagnostic signal and pharmacological effect in response to tumor microenvironment are highly desired. γ-glutamyl transpeptidase (GGT) is a biomarker with significantly up-regulated expression in the tumor area. We developed a GGT responsive near-infrared (NIR) nanoassembly for tumor-specific fluorescence imaging-guided photothermal therapy. Methods: The GGT responsive NIR probe was constructed by conjugating GGT-specific substrate γ-glutamic acid (γ-Glu) with cyanine fluorophore (NRh-NH2) via amide reaction. The resulting NRh-G spontaneously assembled into nanoparticles (NRh-G-NPs) around 50 nm. The NPs were characterized and the properties evaluated in the presence or absence of GGT. Subsequently, we studied fluorescence imaging and photothermal therapy of NRh-G-NPs in vitro and in vivo. Results: NRh-G-NPs, upon specific reaction with GGT, turned into NRh-NH2-NPs, showing a ~180-fold fluorescence enhancement and excellent photothermal effect recovery. NRh-G-NPs could selectively light up U87MG tumor cells while their fluorescence was weak in L02 human normal liver cells. The NPs also showed excellent tumor cell ablation upon laser irradiation. After intravenous injection into tumor-bearing mice, NRh-G-NPs could arrive in the tumor area and specifically light up the tumor. Following laser irradiation, the tumor could be completely erased with no tumor reoccurrence for up to 40 days. Conclusions: NRh-G-NPs were specifically responsive to GGT overexpressed in U87MG tumor cells and selectively lit up the tumor for imaging-guided therapy. Besides, the recovery of photothermal property in the tumor area could improve cancer therapy precision and decreased side effects in normal tissues.


Assuntos
Glioma/tratamento farmacológico , Glioma/radioterapia , Hipertermia Induzida/métodos , Nanopartículas/química , Terapia Fototérmica/métodos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos da radiação , gama-Glutamiltransferase/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Feminino , Fluorescência , Corantes Fluorescentes/química , Ácido Glutâmico/química , Humanos , Lasers , Camundongos , Camundongos Nus , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Espectroscopia de Luz Próxima ao Infravermelho , gama-Glutamiltransferase/genética
13.
Int J Nanomedicine ; 16: 4209-4224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34188470

RESUMO

Background and Purpose: Strontium ranelate (SrR) is an oral pharmaceutical agent for osteoporosis. In recent years, numerous unwanted side effects of oral SrR have been revealed. Therefore, its clinical administration and applications are limited. Hereby, this study aims to develop, formulate, and characterize an effective SrR carrier system for spinal bone regeneration. Methods: Herein, glycol chitosan with hyaluronic acid (HA)-based nanoformulation was used to encapsulate SrR nanoparticles (SrRNPs) through electrostatic interaction. Afterward, the poly(ethylene glycol) diacrylate (PEGDA)-based hydrogels were used to encapsulate pre-synthesized SrRNPs (SrRNPs-H). The scanning electron microscope (SEM), TEM, rheometer, Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were used to characterize prepared formulations. The rabbit osteoblast and a rat spinal decortication models were used to evaluate and assess the developed formulation biocompatibility and therapeutic efficacy. Results: In vitro and in vivo studies for cytotoxicity and bone regeneration were conducted. The cell viability test showed that SrRNPs exerted no cytotoxic effects in osteoblast in vitro. Furthermore, in vivo analysis for new bone regeneration mechanism was carried out on rat decortication models. Radiographical and histological analysis suggested a higher level of bone regeneration in the SrRNPs-H-implanted groups than in the other experimental groups. Conclusion: Local administration of the newly developed formulated SrR could be a promising alternative therapy to enhance bone regeneration in bone-defect sites in future clinical applications.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Portadores de Fármacos/química , Ácido Hialurônico/química , Nanopartículas/química , Polietilenoglicóis/química , Coluna Vertebral/fisiologia , Tiofenos/administração & dosagem , Tiofenos/farmacologia , Animais , Comunicação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacologia , Hidrogéis/química , Masculino , Nanopartículas/ultraestrutura , Tamanho da Partícula , Coelhos , Ratos Wistar , Coluna Vertebral/efeitos dos fármacos
14.
Int J Biol Macromol ; 182: 2024-2036, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34087293

RESUMO

In this study, ramulus mori polysaccharide (RMP) was encapsulated into Poly (lactic-co-glycolicacid) (PLGA) to form PLGA-RMP (PR). The aim of study is to investigate anti-inflammatory effects of PR. The particle size of PR nanoparticles was approximately 205.6 ± 1.86 nm. PR nanoparticles showed significant therapeutic effects on colitis mice model, evidenced by attenuation of the loss of body weight, reduction of the DAI score, and restoration of the colon length. From the histopathological analysis, alleviation of the histopathological damage, less production of IFN-γ and IL-6, and improvement of IL-10 were observed with the treatment of PR. Meanwhile, the treatment of PR not only promoted the expression of ZO-1 and occludin, but also improved the contents of acetate, propionate, and butyrate in the colitis colon. Furthermore, PR extenuated the reduction of the diversity and richness of gut microbiota induced by DSS, and decreased the ratio of Firmicutes to Bacteroidetes while increasing the proportion of Clostridium XIVa, Mucispirillum, and Paraprevotella in the gut microbiota. What's more, PR nanoparticles attenuated the metabolic disorders in the colitis colon induced by DSS. These results indicated that PR nanoparticles could serve as a potent nanomedicine to treat IBD and be used as potential prebiotics.


Assuntos
Anti-Inflamatórios/farmacologia , Morus/química , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polissacarídeos/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/microbiologia , Colite/fisiopatologia , Colo/efeitos dos fármacos , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/fisiopatologia , Camundongos Endogâmicos C57BL , Nanopartículas/ultraestrutura , Tamanho da Partícula , Polissacarídeos/uso terapêutico , Eletricidade Estática , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/patologia
15.
Int J Biol Macromol ; 182: 2066-2075, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34087297

RESUMO

Herein, a novel strategy for surface functionalization and drug loading of cellulose nanocrystals (CNCs) through formation of hydrazone bonds between functionalized CNCs and aldehyde group containing polyethylene glycol (CHO-PEG)/anticancer drug doxorubicin (DOX) was reported for the first time. DOX could be loaded on PEGylated CNCs with high capacity and released from drug complexes (P-CNCs-D) with pH dependent behavior. The biological evaluation results demonstrated that drug carriers (CNCs-EBO-NH) showed negative cytotoxicity while DOX could be transported into cells and exhibits desirable anticancer effects. As compared with other method, the method developed in this work is rather simple and effective and can be achieved for simultaneous for surface functionalization and drug loading in a one-pot route. This work will open a new avenue for fabrication of various multifunctional composites based on other carbohydrate polymers or materials and to explore their applications in biomedical fields.


Assuntos
Celulose/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Espectroscopia Fotoeletrônica , Espectroscopia de Prótons por Ressonância Magnética , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Temperatura , Termogravimetria , Carga Tumoral/efeitos dos fármacos
16.
Int J Biol Macromol ; 182: 2117-2129, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34087305

RESUMO

Biological macromolecules are proven to be potential green corrosion inhibitors because of their outstanding structural features and eco-friendliness. This study is aimed at enhancing their corrosion mitigation capabilities by converting them into nanoparticles. This is the first work where nanoparticles of biological macromolecules are exploited for corrosion mitigation studies. Glycogen nanoparticles (GLY-Np) were synthesized by microwave-mediated nanoprecipitation method and characterized by ATR-FTIR, XRD, UV-Visible Spectroscopy, FESEM analysis, EDX, TEM, and Zeta potential measurements. They are used as an eco-friendly inhibitor for corrosion control of zinc in sulfamic acid (NH2SO3H). The electrochemical study was a primary experimental tool employed for corrosion rate measurement. Conditions were optimized to obtain maximum inhibition efficiency by varying concentrations of inhibitor and temperature. Activation and thermodynamic parameters were evaluated and discussed in detail. A suitable adsorption isotherm was proposed to fit the experimental results. Adsorption of the inhibitor was confirmed by SEM, EDX, and AFM techniques. The inhibition efficiency of 92% was obtained for 0.02 gL-1 GLY-Np. Thus, GLY-Np turned out to be an effective green inhibition with economic benefits.


Assuntos
Glicogênio/química , Nanopartículas/química , Adsorção , Corrosão , Espectroscopia Dielétrica , Eletroquímica , Cinética , Peso Molecular , Nanopartículas/ultraestrutura , Espectrometria por Raios X , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Propriedades de Superfície , Temperatura , Difração de Raios X , Zinco/química
17.
Int J Nanomedicine ; 16: 3755-3773, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34103914

RESUMO

Purpose: Acinetobacter baumannii antibiotic resistant infections in high-risk patients are a great challenge for researchers and clinicians worldwide. In an effort to achieve potent bactericidal outcomes, a novel chitosan-mastoparan nanoconstruct (Mast-Cs NC) was designed and assessed for its therapeutic potential through in silico, in vitro and in vivo experimentation against clinical multidrug-resistant (MDR) A. baumannii. Methods: Optimized 3D structures of mastoparan and chitosan were coupled computationally through an ionic cross-linker to generate a circular ring of chitosan encasing mastoparan. The complex was assessed for interactions and stability through molecular dynamic simulation (MDS). Binding pocket analysis was used to assess the protease-peptide interface. Mast-Cs NC were prepared by the ionic gelation method. Mast-Cs NC were evaluated in vitro and in vivo for their therapeutic efficacy against drug-resistant clinical A. baumannii. Results: MDS for 100 ns showed stable bonds between chitosan and mastoparan; the first at chitosan oxygen atom-46 and mastoparan isoleucine carbon atom with a distance of 2.77 Å, and the second between oxygen atom-23 and mastoparan lysine nitrogen atom with a distance of 2.80 Å, and binding energies of -3.6 and -7.4 kcal/mol, respectively. Mast-Cs complexes approximately 156 nm in size, with +54.9 mV zeta potential and 22.63% loading capacity, offered >90% encapsulation efficiency and were found to be geometrically incompatible with binding pockets of various proteases. The MIC90 of Mast-Cs NC was significantly lower than that of chitosan (4 vs 512 µg/mL, respectively, p<0.05), with noticeable bacterial damage upon morphological analysis. In a BALB/c mouse sepsis model, a significant reduction in bacterial colony count in the Mast-Cs treated group was observed compared with chitosan and mastoparan alone (p<0.005). Mast-Cs maintained good biocompatibility and cytocompatibility. Conclusion: Novel mastoparan-loaded chitosan nanoconstructs signify a successful strategy for achieving a synergistic bactericidal effect and higher therapeutic efficacy against MDR clinical A. baumannii isolates. The Mast-Cs nano-drug delivery system could work as an alternative promising treatment option against MDR A. baumannii.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Quitosana/química , Simulação por Computador , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Nanopartículas/química , Venenos de Vespas/farmacologia , Acinetobacter baumannii/crescimento & desenvolvimento , Acinetobacter baumannii/isolamento & purificação , Adolescente , Adulto , Animais , Antibacterianos/farmacologia , Criança , Pré-Escolar , Modelos Animais de Doenças , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Simulação de Dinâmica Molecular , Nanopartículas/ultraestrutura , Peptídeo Hidrolases/metabolismo , Peptídeos/química , Peptídeos/farmacologia , Adulto Jovem
18.
Int J Mol Sci ; 22(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34062952

RESUMO

BACKGROUND: Dental implants are commonly used for missing teeth, for which success depends heavily on the quality of the alveolar bone. The creation of an ideal implant site is a key component in shortening the treatment time, which remains clinically challenging. Strontium ranelate (Protos) is an anti-osteoporotic agent which has previously been used to promote bone formation, however the systemic use of Protos has been linked to serious cardiovascular and venous thromboembolic events, thus local delivery strategies may be better suited for this purpose. In this study, a biodegradable, and biocompatible nanocarrier "polybutylcyanoacrylate" (PBCA) loaded with strontium was constructed and its ability to promote bone formation was assessed. METHODOLOGY: PBCA nanoparticles loaded with strontium (PBCA-Sr NPs) were synthesized using the emulsion polymerization method, and their physical properties (zeta potential, size and shape) and entrapment efficiency were characterized. Committed MSCs (osteoblasts) were derived from the differentiation of cultured rat mesenchymal stem cells (MSC), which were tested with the PBCA-Sr NPs for cytotoxicity, inflammatory response, bone formation and mineralization. Scanning electron microscopy was performed following a 7-day treatment of PBCA-Sr NPs on decellularized procaine mandibular bone blocks grafted with osteoblasts. RESULTS: Spherical PBCA-Sr NPs of 166.7 ± 2.3 nm, zeta potential of -1.15 ± 0.28 mV with a strontium loading efficiency of 90.04 ± 3.27% were constructed. The presence of strontium was confirmed by energy-dispersive X-ray spectroscopy. Rat committed MSCs incubated in PBCA-Sr NPs for 24 hrs showed viabilities in excess of 90% for concentrations of up to 250 ug/mL, the cellular expression of osteocalcin and alkaline phosphatase were 1.4 and 1.3 times higher than the untreated control, and significantly higher than those treated with strontium alone. Bone formation was evident following osteoblast engraftment on the decellularized procaine mandibular bone block with PBCA-Sr NPs, which appeared superior to those treated with strontium alone. CONCLUSION: Treatment of committed MSCs with PBCA-Sr NPs showed higher expression of markers of bone formation when compared with strontium alone and which corresponded to greater degree of bone formation observed on the 3-dimensinal decellularized procaine mandibular bone block. Further quantitative analysis on the extent of new bone formation is warranted.


Assuntos
Embucrilato/química , Mandíbula/crescimento & desenvolvimento , Nanopartículas/química , Osteogênese , Tiofenos/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Mandíbula/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas/ultraestrutura , Imagem Óptica , Osteocalcina/metabolismo , Tamanho da Partícula , Ratos Sprague-Dawley , Eletricidade Estática
19.
Molecules ; 26(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064416

RESUMO

The objective of this study was to synthesize and characterize a set of biodegradable block copolymers based on TPGS-block-poly(ε-caprolactone) (TPGS-b-PCL) and to assess their self-assembled structures as a nanodelivery system for paclitaxel (PAX). The conjugation of PCL to TPGS was hypothesized to increase the stability and the drug solubilization characteristics of TPGS micelles. TPGS-b-PCL copolymer with various PCL/TPGS ratios were synthesized via ring opening bulk polymerization of ε-caprolactone using TPGS, with different molecular weights of PEG (1-5 kDa), as initiators and stannous octoate as a catalyst. The synthesized copolymers were characterized using 1H NMR, GPC, FTIR, XRD, and DSC. Assembly of block copolymers was achieved via the cosolvent evaporation method. The self-assembled structures were characterized for their size, polydispersity, and CMC using dynamic light scattering (DLS) technique. The results from the spectroscopic and thermal analyses confirmed the successful synthesis of the copolymers. Only copolymers that consisted of TPGS with PEG molecular weights ≥ 2000 Da were able to self-assemble and form nanocarriers of ≤200 nm in diameter. Moreover, TPGS2000-b-PCL4000, TPGS3500-b-PCL7000, and TPGS5000-b-PCL15000 micelles enhanced the aqueous solubility of PAX from 0.3 µg/mL up to 88.4 ug/mL in TPGS5000-b-PCL15000. Of the abovementioned micellar formulations, TPGS5000-b-PCL15000 showed the slowest in vitro release of PAX. Specifically, the PAX-loaded TPGS5000-b-PCL15000 micellar formulation showed less than 10% drug release within the first 12 h, and around 36% cumulative drug release within 72 h compared to 61% and 100% PAX release, respectively, from the commercially available formulation (Ebetaxel®) at the same time points. Our results point to a great potential for TPGS-b-PCL micelles to efficiently solubilize and control the release of PAX.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/farmacologia , Poliésteres/química , Vitamina E/química , Varredura Diferencial de Calorimetria , Cromatografia em Gel , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Micelas , Nanopartículas/ultraestrutura , Tamanho da Partícula , Poliésteres/síntese química , Espectroscopia de Prótons por Ressonância Magnética , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Vitamina E/síntese química , Água/química , Difração de Raios X
20.
Molecules ; 26(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068039

RESUMO

The development of greener nano-constructs with noteworthy biological activity is of supreme interest, as a robust choice to minimize the extensive use of synthetic drugs. Essential oils (EOs) and their constituents offer medicinal potentialities because of their extensive biological activity, including the inhibition of fungi species. However, their application as natural antifungal agents are limited due to their volatility, low stability, and restricted administration routes. Nanotechnology is receiving particular attention to overcome the drawbacks of EOs such as volatility, degradation, and high sensitivity to environmental/external factors. For the aforementioned reasons, nanoencapsulation of bioactive compounds, for instance, EOs, facilitates protection and controlled-release attributes. Nanoliposomes are bilayer vesicles, at nanoscale, composed of phospholipids, and can encapsulate hydrophilic and hydrophobic compounds. Considering the above critiques, herein, we report the in-house fabrication and nano-size characterization of bioactive oregano essential oil (Origanum vulgare L.) (OEO) molecules loaded with small unilamellar vesicles (SUV) nanoliposomes. The study was focused on three main points: (1) multi-compositional fabrication nanoliposomes using a thin film hydration-sonication method; (2) nano-size characterization using various analytical and imaging techniques; and (3) antifungal efficacy of as-developed OEO nanoliposomes against Trichophyton rubrum (T. rubrum) by performing the mycelial growth inhibition test (MGI). The mean size of the nanoliposomes was around 77.46 ± 0.66 nm and 110.4 ± 0.98 nm, polydispersity index (PdI) of 0.413 ± 0.015, zeta potential values up to -36.94 ± 0.36 mV were obtained by dynamic light scattering (DLS). and spherical morphology was confirmed by scanning electron microscopy (SEM). The presence of OEO into nanoliposomes was displayed by attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. Entrapment efficiency values of 79.55 ± 6.9% were achieved for OEO nanoliposomes. In vitro antifungal activity of nanoliposomes tested against T. rubrum strains revealed that OEO nanoliposomes exhibited the highest MGI, 81.66 ± 0.86%, at a concentration of 1.5 µL/mL compared to the rest of the formulations. In summary, this work showed that bioactive OEO molecules with loaded nanoliposomes could be used as natural antifungal agents for therapeutical purposes against T. rubrum.


Assuntos
Antifúngicos/farmacologia , Nanopartículas/química , Óleos Voláteis/química , Origanum/química , Tamanho da Partícula , Fungos/efeitos dos fármacos , Micélio/efeitos dos fármacos , Micélio/crescimento & desenvolvimento , Nanopartículas/ultraestrutura , Fosfatidilcolinas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Lipossomas Unilamelares
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...