Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 39.228
Filtrar
1.
Medicine (Baltimore) ; 98(36): e16935, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490376

RESUMO

BACKGROUND: Although several previous studies demonstrated the feasibility and efficacy of indocyanine green (ICG) for thyroid cancer surgery, ICG was administered through venous injection and focused on parathyroid gland protection. We thus aimed to study the feasibility of imaging using ICG combined with carbon nanoparticles (CNs) in the identification of sentinel lymph nodes (SLNs) in patients diagnosed with papillary thyroid microcarcinoma (PTMC). METHODS: Two approaches were applied to detect lymph nodes in PTMC surgery. Patients were randomized into 2 groups. ICG and CNs were injected into the thyroid in Group A. In Group B, only CNs was injected. Black-stained or fluorescent nodes observed using near-infrared fluorescence imaging systems were defined as SLNs. SLN and central lymph node (CLN) dissection was completed in both groups. The pathological and postoperative outcomes were compared between 2 groups. RESULTS: There were 40 patients in Group A and 60 in Group B. A total of 138 SLNs were identified; 72 and 66 SLNs were detected and dissected in Groups A and B, respectively. The number of SLNs identified (per patient) in Group A was higher than that in Group B (P = .027). The number of harvested CLNs was 161 and 192 in Groups A and B, respectively, out of which 45 and 48 lymph nodes with metastasis were confirmed by permanent pathology. The CLN metastatic rate in Group A was higher than that in Group B (P = .048). CONCLUSION: Imaging using ICG combined CNs is feasible and safe for SLN identification in PTMC patients. Compared with using only CNs, more SLNs can be removed and more metastatic lymph nodes can be confirmed when using the combined method. Although the combined method appears to accurately stage tumors, further research is needed.


Assuntos
Carbono/administração & dosagem , Carcinoma Papilar/patologia , Verde de Indocianina/administração & dosagem , Excisão de Linfonodo/métodos , Nanopartículas/administração & dosagem , Linfonodo Sentinela/cirurgia , Neoplasias da Glândula Tireoide/patologia , Adulto , Carbono/química , Carcinoma Papilar/cirurgia , Corantes/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Nanopartículas/química , Imagem Óptica/métodos , Linfonodo Sentinela/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos
2.
Int J Nanomedicine ; 14: 4911-4929, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456637

RESUMO

Background: Apocynin (APO) is a bioactive phytochemical with prominent anti-inflammatory and anti-oxidant activities. Designing a nano-delivery system targeted to potentiate the gastric antiulcerogenic activity of APO has not been investigated yet. Chitosan oligosaccharide (COS) is a low molecular weight chitosan and its oral nanoparticulate system for potentiating the antiulcerogenic activity of the loaded APO has been described here. Methods: COS-nanoparticles (NPs) loaded with APO (using tripolyphosphate [TPP] as a cross-linker) were prepared by ionic gelation method and fully characterized. The chosen formula was extensively evaluated regarding in vitro release profile, kinetic analysis, and stability at refrigerated and room temperatures. Ultimately, the in vivo antiulcerogenic activity against ketoprofen (KP)-induced gastric ulceration in rats was assessed by macroscopic parameters including Paul's index and antiulcerogenic activity, histopathological examination, immunohistochemical (IHC) evaluation of cyclooxygenase-2 (COX-2) expression level in ulcerated gastric tissue, and biochemical measurement of oxidative stress markers and nitric oxide (NO) levels. Results: The selected NPs formula with COS (0.5 % w/v) and TPP (0.1% w/v) was the most appropriate one with drug entrapment efficiency percentage of 35.06%, particle size of 436.20 nm, zeta potential of +38.20 mV, and mucoadhesive strength of 51.22%. It exhibited a biphasic in vitro release pattern as well as high stability at refrigerated temperature for a 6-month storage period. APO-loaded COS-NPs provoked marvelous antiulcerogenic activity against KP-induced gastric ulceration in rats compared with free APO treated group, which was emphasized by histopathological, IHC, and biochemical studies. Conclusion: In conclusion, APO-loaded COS-NPs could be considered as a promising oral phytopharmaceutical nanoparticulate system for management of gastric ulceration.


Assuntos
Acetofenonas/administração & dosagem , Acetofenonas/farmacologia , Quitosana/química , Mucosa Gástrica/efeitos dos fármacos , Nanopartículas/química , Oligossacarídeos/química , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/farmacologia , Acetofenonas/uso terapêutico , Administração através da Mucosa , Animais , Biomarcadores/metabolismo , Varredura Diferencial de Calorimetria , Ciclo-Oxigenase 2/metabolismo , Liberação Controlada de Fármacos , Cinética , Masculino , Nanopartículas/ultraestrutura , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Suínos , Difração de Raios X
3.
Chem Commun (Camb) ; 55(66): 9829-9832, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31363730

RESUMO

Polyethylene glycol grafted pyrrole-based conjugated polymers are synthesized through a one-pot multicomponent methodology, the self-assemblies of which enable nanoparticle size-selective encapsulation of drug molecules and their sustained release. Efficient loading of curcumin through drug-nanoparticle core interactions is probed using FRET, and the inherently fluorescent nature of polypyrrole could be used to detect these nanocarriers intracellularly.


Assuntos
Portadores de Fármacos , Nanopartículas/química , Polietilenoglicóis/química , Polímeros/química , Pirróis/química , Linhagem Celular Tumoral , Curcumina/administração & dosagem , Transferência Ressonante de Energia de Fluorescência , Humanos , Interações Hidrofóbicas e Hidrofílicas , Concentração Inibidora 50 , Microscopia Eletrônica de Transmissão , Espectrofotometria Ultravioleta
4.
Bioresour Technol ; 291: 121842, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31377505

RESUMO

The spherical cellulose nanocrystals (CNCs) with high purity were prepared, the processes included composite enzymolysis of pulp fibers and the purification of product. The impurities in the crude product CNCs were analyzed with FTIR, coomassie brilliant blue-G250 and ionic chromatography. The pure CNCs were characterized with SEM, XRD, DLS and TGA. The results indicated that the crude CNCs was flocculated and washed twice with a dilute acid solution (pH = 2) to get pure spherical CNCs, the purity was approximate 99.99%. The obtained pure spherical CNCs had a narrow particle size distribution with diameter 15-40 nm. FTIR and XRD analyses proved that the crystal phase of the spherical CNCs did not change, but the crystallinity decreased slightly compared with pulp fibers. The thermal degradation showed that the spherical CNCs had better thermal stability than one from other methods, and the temperature of maximum weight loss rate (Tmax) was 329.2 °C.


Assuntos
Celulose/química , Nanopartículas/química , Temperatura Alta , Papel , Espectroscopia de Infravermelho com Transformada de Fourier
5.
World J Microbiol Biotechnol ; 35(8): 125, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363859

RESUMO

The global need to develop sustainable materials and products from non-fossil raw material is pushing industry to utilize side-streams more efficiently using green processes. Aromatic lignin, the world's second most abundant biopolymer, has multiple attractive properties which can be exploited in various ways instead of being burnt or used as animal feed. Lignin's poor water solubility and its highly branched and random structure make it a challenging biopolymer to exploit when developing novel technologies for the preparation of tailored nanobiomaterials for value-added applications. The notable number of scientific publications focusing on the formation and modification of technical lignin in nanoparticulate morphology show that these bottlenecks could be solved using lignin in the form of colloidal particles (CLPs). These particles are very stable at wide pH range (4-11) and easily dispersible in organic solvents after stabilized via cross-linking. Negative hydroxyl groups on the CLP surface enable multiple enzymatic and chemical modifications e.g. via polymerization reactions and surface-coating with positive polymers. This contribution highlights how tailored CLPs could be innovatively exploited in different the state-of-the-art applications such as medicine, foods, and cosmetics.


Assuntos
Química Verde/métodos , Lignina/síntese química , Lignina/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Animais , Biotransformação , Solubilidade
6.
J Agric Food Chem ; 67(33): 9371-9381, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31379162

RESUMO

A major obstacle to the clinical use of curcumin (CUR) is its reduced bioavailability because of the drug's hydrophobic nature, low intestinal absorption, and rapid metabolism. In this study, a novel oral drug delivery system was constructed for improving the stability and enhancing mucoadhesion of CUR in the gastrointestinal (GI) tract. First, CUR was encapsulated in the bovine serum albumin nanoparticles (CUR-BSA-NPs). Then, N-acetyl cysteine (NAC)-modified CUR-BSA-NPs (CUR-NBSA-NPs) were obtained. The average particle size and zeta potential of CUR-NBSA-NPs were 251.6 nm and -30.66 mV, respectively; encapsulation efficiency and drug loading were 85.79 and 10.9%, respectively. CUR-NBSA-NPs exhibited a sustained release property and prominently enhanced stability in simulated GI conditions. Additionally, enhanced mucoadhesion of CUR-NBSA-NPs was also observed. An MTT study showed that the CUR-NBSA-NPs were safe for oral administration. Overall, NAC-modified BSA-NPs may potentially serve as an oral vehicle for improving CUR stability in the GI tract and enhancing mucoadhesion.


Assuntos
Acetilcisteína/química , Curcumina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/instrumentação , Trato Gastrointestinal/metabolismo , Nanopartículas/química , Soroalbumina Bovina/química , Animais , Células CACO-2 , Bovinos , Curcumina/metabolismo , Estabilidade de Medicamentos , Humanos , Tamanho da Partícula
7.
Pharm Res ; 36(10): 142, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31376020

RESUMO

BACKGROUND: With the recent approval of the first small interfering RNA (siRNA) therapeutic formulated as nanoparticles, there is increased incentive for establishing the factors of importance for the design of stable solid dosage forms of such complex nanomedicines. METHODS: The aims of this study were: (i) to identify factors of importance for the design of spray-dried siRNA-loaded lipidoid-poly(DL-lactic-co-glycolic acid) hybrid nanoparticles (LPNs), and (ii) to evaluate their influence on the resulting powders by using a quality-by-design approach. Critical formulation and process parameters were linked to critical quality attributes (CQAs) using design of experiments, and an optimal operating space (OOS) was identified. RESULTS: A series of CQAs were identified based on the quality target product profile. The loading (ratio of LPNs to the total solid content) and the feedstock concentration were determined as critical parameters, which were optimized systematically. Mannitol was chosen as stabilizing excipient due to the low water content of the resulting powders. The loading negatively affected the colloidal stability of the LPNs, whereas feedstock concentration correlated positively with the powder particle size. The optimal mannitol-based solid formulation, defined from the OOS, displayed a loading of 5% (w/w), mass median aerodynamic diameter of 3.3 ± 0.2 µm, yield of 60.6 ± 6.6%, and a size ratio of 1.15 ± 0.03. Dispersed micro-embedded LPNs had preserved physicochemical characteristics as well as in vitro siRNA release profile and gene silencing, as compared to non-spray-dried LPNs. CONCLUSION: The optimal solid dosage forms represent robust formulations suitable for higher scale-up manufacturing.


Assuntos
Dessecação/métodos , Lipídeos/química , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , RNA Interferente Pequeno/química , Administração por Inalação , Animais , Composição de Medicamentos , Excipientes/química , Inativação Gênica , Técnicas de Transferência de Genes , Manitol/química , Camundongos , Nanomedicina , Tamanho da Partícula , Pós , Células RAW 264.7 , RNA Interferente Pequeno/administração & dosagem , Solubilidade , Solventes/química
8.
Pharm Res ; 36(10): 143, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31385111

RESUMO

PURPOSE: Pancreatic Polypeptide-secreting tumor of the distal pancreas (PPoma) is a rare, difficult and indolent type of cancer with a survival rate of 5-year in only 10% of all cases. The PPoma is classified as a neuroendocrine tumor (NET) not functioning that overexpresses SSTR 2 (somatostatin receptor subtype 2). Thus, in order to improve the diagnosis of this type of tumor, we developed nanoparticulate drug carriers based on poly-lactic acid (PLA) polymer loaded with octreotide and radiolabeled with Technetium-99 m (99mTc). METHODS: PLA/PVA octreotide nanoparticles were developed by double-emulsion technique. These nanoparticles were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) and radiolabeled with 99mTc by the direct via forming 99mTc-PLA/PVA octreotide nanoparticles. The safety of these nanosystems was evaluated by the MTT cell toxicity assay and their in vivo biodistribution was evaluated in xenografted inducted animals. RESULTS: The results showed that a 189 nm sized nanoparticle were formed with a PDI of 0,097, corroborating the monodispersive behavior. These nanoparticles were successfully radiolabeled with 99mTc showing uptake by the inducted tumor. The MTT assay corroborated the safety of the nanosystem for the cells. CONCLUSION: The results support the use of this nanosystem (99mTc-PLA/PVA octreotide nanoparticles) as imaging agent for PPoma. Graphical Abstract Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma) Radiolabeled Nanoparticles for Imaging.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico por imagem , Nanopartículas/química , Octreotida/química , Neoplasias Pancreáticas/diagnóstico por imagem , Polipeptídeo Pancreático/metabolismo , Poliésteres/química , Compostos Radiofarmacêuticos/química , Tecnécio/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/metabolismo , Octreotida/metabolismo , Pâncreas/diagnóstico por imagem , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Tamanho da Partícula , Cintilografia/métodos , Compostos Radiofarmacêuticos/metabolismo , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Distribuição Tecidual
9.
Life Sci ; 234: 116756, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419444

RESUMO

AIMS: Conventional radiotherapy is mainly restricted by the low radiation absorption efficiency of tumors tissues and the hypoxic tumor cells radio-resistance. In this paper, novel nano-radiosensitizers, magnetic nanoparticles core coated with silica, were successfully prepared to overcome these limitations. MAIN METHODS: The prepared nanoparticles have been characterized by transmission electron microscope (TEM), Dynamic light scattering (DLS), atomic force microscope (AFM) and vibration sample magnetometer (VSM). MTT cytotoxicity and DNA double-strand breaks (Comet) assays have been used to assess the radio-enhancing effect of iron oxide magnetic nanoparticles (IO-MNPs) and silica-coated iron oxide magnetic nanoparticles (SIO-MNPs) against MCF7 breast cancer cells. MCF7 cells were treated with different concentrations of the prepared nanoformulations and exposed to an electron beam at doses 0, 0.5, 1, 2, 4 Gy. KEY FINDINGS: DLS measurements revealed that the main hydrodynamic diameter of the prepared IO-MNPs and SIO-MNPs was 18.17 ±â€¯4.5 nm and 164.18 ±â€¯16.1 nm, respectively, which was confirmed by TEM micrographs. MTT and comet assays results showed that the radiosensitizing effect of the prepared nanoformulations was dose and concentration dependent. Interestingly, the dose enhancement factor (DEF) for SIO-MNPs was, on average, 1.3-fold greater than that of IO-MNPs. SIGNIFICANCE: Coating of IO-MNPs with silica led to enhance their electron radiosensitization and consequently their therapeutic efficacy. Therefore, SIO-MNPs represent a promising engineered nano-formulation for enhancing breast cancer radiosensitivity.


Assuntos
Neoplasias da Mama/radioterapia , Compostos Férricos/uso terapêutico , Nanopartículas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Dióxido de Silício/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos da radiação , Dano ao DNA/efeitos da radiação , Elétrons , Feminino , Compostos Férricos/química , Humanos , Células MCF-7 , Nanopartículas/química , Radiossensibilizantes/química , Dióxido de Silício/química
10.
Life Sci ; 234: 116758, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421083

RESUMO

In this work, fluorescent copper oxide nanoparticles (CuO NPs) were green synthesized using viable cells, cell lysate supernatant (CLS) and protein extracts of luminescent Vibrio sp. VLC. Biogenic CuO NPs were then characterized by XRD, FTIR, UV/Vis spectroscopy, TEM, DLS, and PL spectroscopy. Results showed that CLS method was more efficient for CuO NPs production, therefore CuO NPs synthesized by this method from copper sulfate (CuO NPs-1) and/or copper nitrate (CuO NPs-2) were used for further studies. The crystallite size of polydispersed CuO NPs-1 and CuO NPs-2 were about 8.83 and 8.77 nm, respectively indicating their suitability for biological applications. Antibacterial activity of CuO NPs was determined using broth microdilution, well diffusion agar, and time-kill curves methods. Both CuO NP-1 and CuO NP-2 inhibited bacterial growth at the minimum inhibitory concentration (MIC) of 625 mg/L except St. mutants (MIC = 1250 mg/L). Emission of fluorescent light from the surface of NPs was increased when exposed to Cd2+, As2+ and Hg2+ ions but decreased by Pb2+ ions. Results showed that CuO NP-1 had anticancer properties against KYSE30 esophageal cancer cell line (IC50 = 13.96 mg/L) while no higher cytotoxic effects were observed on Human Dermal Fibroblasts (HDF) (IC50 = 48.88 mg/L).


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Cobre/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Corantes Fluorescentes/química , Metais Pesados/análise , Nanopartículas/química , Antibacterianos/química , Antineoplásicos/química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Linhagem Celular Tumoral , Cobre/química , Química Verde/métodos , Humanos , Espectrometria de Fluorescência/métodos , Vibrio/química
11.
J Agric Food Chem ; 67(37): 10432-10447, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31466447

RESUMO

A composite nanogel was developed for cyanidin-3-O-glucoside (C3G) delivery by combining Maillard reaction and heat gelation. The starting materials utilized were ovalbumin, dextran, and pectin. C3G-loaded nanogel was spherical with a diameter of ∼185 nm, which was maintained over a wide range of pH and NaCl concentrations. The composite nanogel enhanced the chemical stability of C3G under accelerated degradation models and a simulated gastrointestinal tract. Clathrin-mediated, caveolae-mediated, and macropinocytosis-related endocytosis contributed to the higher cellular uptake of nano-C3G than that of free-C3G. The apparent permeability coefficients of C3G increased 2.16 times after nanoencapsulation. The transcytosis of the C3G-bearing nanogel occurred primarily through the clathrin-related pathway and macropinocytosis and followed the "common recycling endosomes-endoplasmic reticulum-Golgi complex-basolateral plasma membrane" route. Moreover, nano-C3G was more efficient in restoring the viability of cells and activities of endogenous antioxidant enzymes than free-C3G in oxidative models, which may be attributed to the former's high cellular absorption.


Assuntos
Antocianinas/química , Antocianinas/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Portadores de Fármacos/química , Glucosídeos/química , Glucosídeos/metabolismo , Células CACO-2 , Composição de Medicamentos , Estabilidade de Medicamentos , Trato Gastrointestinal/metabolismo , Géis/química , Géis/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Absorção Intestinal , Modelos Biológicos , Nanopartículas/química , Nanopartículas/metabolismo , Tamanho da Partícula
12.
J Agric Food Chem ; 67(37): 10470-10480, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31469565

RESUMO

Foodborne nanoparticles (FNPs) produced by roasting have attracted the attention of people, owing to their safety risk to body health. Herein, we reported the formation, physicochemical properties, elemental composition, biodistribution, and binding with human serum albumin (HSA) of FNPs extracted from roast squid. The results showed that the FNP size gradually decreased from 4.1 to 2.3 nm as the roasting temperature changed from 190 to 250 °C. The main component elements of FNPs are carbon, oxygen, and nitrogen, and the carbon and nitrogen contents of FNPs increased with the roasting temperature rising. The surface of FNPs contained hydroxyl, amino, and carboxyl functional groups. The FNPs can emit fluorescence in ultraviolet light and show excitation-dependent emission behavior. Furthermore, it was found that the FNPs derived from roast squid could be accumulated in the stomach, intestine, and brain of BALB/c mice after oral feeding. Static fluorescence quenching of HSA was found by the Stern-Volmer equation and ultraviolet-visible spectrum analysis after interaction with the FNPs. After the addition of FNPs, the α-helix content of HSA decreased and the morphological height of HSA increased, which indicated that the FNPs could cause structural changes in HSA. The atomic force microscopy characterization showed the formation of nanocorona between FNPs and HSA.


Assuntos
Decapodiformes/química , Nanopartículas/química , Nanopartículas/metabolismo , Albumina Sérica Humana/química , Animais , Culinária , Decapodiformes/metabolismo , Fluorescência , Temperatura Alta , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Força Atômica , Tamanho da Partícula , Ligação Proteica , Conformação Proteica , Albumina Sérica Humana/metabolismo , Distribuição Tecidual
13.
Pharm Res ; 36(11): 152, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31463609

RESUMO

PURPOSE: To develop an analytical platform for the estimation as well as characterization of aggregates over the complete size spectrum (from invisible monomer to visible precipitates). METHODS: Two mAb samples were incubated at 30°C in different buffer systems of protein A chromatography for observing degradation due to aggregation. The aggregation in these samples was quantified by size exclusion chromatography (SEC), dynamic light scattering (DLS), and micro flow imaging (MFI). RESULTS: The results obtained from various characterization tools were analysed in various size ranges - size exclusion chromatography (SEC) (1 nm - 25 nm), dynamic light scattering (DLS) (10 nm - 5 µm), and micro flow imaging (MFI) (2 µm - 300 µm). Since each characterization tool covers a particular size range, data from multiple tools was collected in the "handover" regions to demonstrate accuracy of the platform. CONCLUSIONS: Based on the observations from the experiments, an analytical platform has been proposed covering the whole size spectrum that would be of utility to those engaged in formulation development as well as other aspects related to stability of biotherapeutic products.


Assuntos
Anticorpos Monoclonais/análise , Tampões (Química) , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Difusão Dinâmica da Luz , Nanopartículas/química , Tamanho da Partícula , Multimerização Proteica , Estabilidade Proteica
14.
Pharm Res ; 36(10): 145, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31396764

RESUMO

PURPOSE: The immediate plasma metabolism and development of chemo-resistance (single agent) severely hampers the clinical effectiveness of Sorafenib (SRF) in liver cancer therapy. MicroRNA27a inhibition is a promising biological strategy for breast cancer therapy. METHODS: In this study, we aimed to prepare SRF and anti-miRNA27a-loaded anti-GPC3 antibody targeted lipid nanoparticles to enhance the therapeutic efficacy against liver cancers. In this study, we have employed a unique cationic switchable lipid (CSL) as a mean to encapsulate miRNA as well as to confer pH-responsiveness to the nanocarrier system. RESULTS: The G-S27LN was nanosized and offered a pH-responsive release of SRF from the carrier system and we have demonstrated the specific affinity of G-S27LN towards the GPC3-overexpressed HepG2 cancer cells. Anti-microRNA27a significantly increased the protein expression of FOXO1 and PPAR-γ which are crucial components involved in proliferation and apoptosis of tumor cells. Combination of SRF and anti-miRNA27a (G-S27LN) resulted in significantly lower cell viability with a marked increase in the apoptosis cell proportion compared to that of free SRF indicating the synergistic anticancer effect. Animal studies in liver cancer xenograft model demonstrated significant suppression of tumor burden, reduced tumor cell and elevated TUNEL positive apoptosis with no toxicity concerns in animals treated with G-S27LN formulation. CONCLUSION: The CSL-based G-S27LN efficiently co-delivered anti-microRNA27a and SRF and therefore represents a promising therapy to treat liver cancer. This study also brings forth a platform strategy for the effective treatment of number of other advanced cancers.


Assuntos
Antagomirs/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Glipicanas/imunologia , Lipídeos/química , Neoplasias Hepáticas/tratamento farmacológico , MicroRNAs/imunologia , Nanopartículas/química , Sorafenibe/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colesterol/química , Sinergismo Farmacológico , Proteína Forkhead Box O1/metabolismo , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos BALB C , Camundongos Nus , PPAR gama/metabolismo , Fosforilcolina/química , Polietilenoglicóis/química
15.
Chem Biol Interact ; 311: 108774, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31369748

RESUMO

Silica nanoparticles (SiNPs) are one of the popular nanomaterials used in industrial manufacturing, synthesis, engineering, and medicine. Recently, mechanisms underlying toxicity of silica nanoparticles have been reported; however, their uptake mechanisms have still not fully understood. In this study, toxicity of SiNPs was investigated in the nematode Caenohabditis elegans by using microarray and pathway analysis focusing the uptake mechanisms and their impact on toxicity. Physicochemical characterization of SiNPs was performed using dynamic light scattering (DLS) and zeta potential. No mortality was observed after 24 h exposure to SiNPs. However, reproductive ability was significantly reduced at the same concentrations. To ascertain a global mechanism of toxicity, microarray was conducted on C. elegans exposed to 10 mg/L SiNPs (20% reduction in reproductive ability). Microarray results indicated that genes involved in reproduction, such as msp (Major Sperm Protein) genes, were significantly downregulated in C. elegans exposed to SiNPs. Pathway analyses on differentially expressed genes (DEGs) revealed that endocytic pathway as a major pathway involved in the uptake of SiNPs. Involvement of endocytic pathway in the uptake of SiNPs was assessed using specific inhibitors (methyl-ß-cyclodextrin, chlorpromazine, and LY294002 for caveolin-, clathrin-, and pinocytosis-mediated endocytosis, respectively). The inhibitor assay indicated that an internalization process facilitated by clathrin-mediated endocytosis is involved in the uptake of SiNPs. Functional analysis using endocytosis defective mutants, (i,e.  cav-1, cup-2, and chc-1) confirmed the role of endocytosis on the reproductive toxicity of SiNPs. Overall results suggest that clathrin-mediated endocytosis pathway is a potential mechanism of uptake of SiNPs in C. elegans that in turn, affects general toxic outcome, such as, decrease in reproductive ability.


Assuntos
Caenorhabditis elegans/metabolismo , Clatrina/metabolismo , Endocitose/efeitos dos fármacos , Nanopartículas/toxicidade , Dióxido de Silício/química , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Redes Reguladoras de Genes/efeitos dos fármacos , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Reprodução/efeitos dos fármacos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacologia
16.
Int J Nanomedicine ; 14: 4931-4947, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371941

RESUMO

Background: Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), is a promising noninvasive strategy in the treatment of cancers due to its highly localized specificity to tumors and minimal side effects to normal tissues. However, single phototherapy often causes tumor recurrence which hinders its clinical applications. Therefore, developing a NIR-guided dendritic nanoplatform for improving the phototherapy effect and reducing the recurrence of tumors by synergistic chemotherapy and phototherapy is essential. Methods: A fluorescent targeting ligand, insisting of ICG derivative cypate and a tumor penetration peptide iRGD (CRGDKGPDC), was covalently combined with PAMAM dendrimer to prepare a single agent-based dendritic theranostic nanoplatform iRGD-cypate-PAMAM-DTX (RCPD). Results: Compared with free cypate, the resulted RCPD could generate enhanced singlet oxygen species while maintaining its fluorescence intensity and heat generation ability when subjected to NIR irradiation. Furthermore, our in vitro and in vivo therapeutic studies demonstrated that compared with phototherapy or chemotherapy alone, the combinatorial chemo-photo treatment of RCPD with the local exposure of NIR light can significantly improve anti-tumor efficiency and reduce the risk of recurrence of tumors. Conclusion: The multifunctional theranostic platform (RCPD) could be used as a promising method for NIR fluorescence image-guided combinatorial treatment of tumor cancers.


Assuntos
Antineoplásicos/farmacologia , Dendrímeros/química , Raios Infravermelhos , Nanopartículas/química , Fototerapia , Animais , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Docetaxel/farmacologia , Endocitose/efeitos dos fármacos , Fluorescência , Células Hep G2 , Temperatura Alta , Humanos , Indóis/farmacologia , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Oligopeptídeos/química , Fotoquimioterapia , Propionatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica
17.
Int J Nanomedicine ; 14: 5159-5173, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371954

RESUMO

Introduction: The use of liposomes as a drug delivery carrier (DDC) for the treatment of various diseases, especially cancer, is rapidly increasing, requiring more stringent synthesis, formulation, and preservation techniques to bolster safety and efficacy. Liposomes otherwise referred to as phospholipid vesicles are self-assembled colloidal particles. When formed in either the micrometer or nanometer size range, they are ideal candidates as DDC because of their biological availability, performance, activity, and compatibility. Defining and addressing the critical quality attributes (CQAs) along the pharmaceutical production scale will enable a higher level of quality control for reproducibility. More specifically, understanding the CQAs of nanoliposomes that dictate its homogeneity and stability has the potential to widen applications in biomedical science. Methods: To this end, we designed a study that aimed to define synthesis, characterization, formulation (encapsulation), preservation, and cargo delivery and trafficking as the major components within a target product profile for nanoliposomes. A series of synthetic schemes were employed to measure physicochemical properties relevant to nanomaterial drug product development, including concentration gradients, probe versus bath sonication, and storage temperature measured by microscopy (electron and light) and dynamic light scattering. Results: Concentration was found to be a vital CQA as reducing concentrations resulted in nanometer-sized liposomes of <350 nm. Liposomes were loaded with microRNA and fluorescence spectroscopy was used to determine loading efficacy and stability over time. Lyophilization was used to create a dry powder formulation that was then assessed for stability for 6 months. Lastly, breast cancer cell lines were used to ensure efficacy of microRNA delivery and localization. Conclusion: We conclude that microRNA can be loaded into nanometer-sized liposomes, preserved for months in a dried form, and maintain encapsulation after extended time periods in storage.


Assuntos
Neoplasias da Mama/terapia , Lipossomos/química , MicroRNAs/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , Linhagem Celular Tumoral , Feminino , Humanos , Nanopartículas/ultraestrutura , Concentração Osmolar , Reprodutibilidade dos Testes
18.
Int J Nanomedicine ; 14: 5381-5396, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409994

RESUMO

Background: Tacrolimus (TCR), also known as FK-506, is a biopharmaceutics classification system (BCS) class II drug that is insoluble in water because of its high log P values. After dermal application, TCR remains in the stratum corneum and passes through the skin layers with difficulty. Purpose: The objectives of this study were to develop and evaluate solid lipid nanoparticles (SLNs) with thermosensitive properties to improve penetration and retention. Methods: We prepared TCR-loaded thermosensitive solid lipid nanoparticles (TCR-SLNs) with different types of surfactants on the shell of the particle, which conferred the advantages of enhancing skin permeation and distribution. We also characterized them from a physic point of view and performed in vitro and in vivo evaluations. Results: The TCR contained in the prepared TCR-SLN was in an amorphous state and entrapped in the particles with a high loading efficiency. The assessment of ex vivo skin penetration using excised rat dorsal skin showed that the TCR-SLNs penetrated to a deeper layer than the reference product (0.1% Protopic®). In addition, the in vivo skin penetration test demonstrated that TCR-SLNs delivered more drug into deeper skin layers than the reference product. FT-IR images also confirmed drug distribution of TCR-SLNs into deeper layers of the skin. Conclusion: These results revealed the potential application of thermosensitive SLNs for the delivery of difficult-to-permeate, poorly water-soluble drugs into deep skin layers.


Assuntos
Derme/metabolismo , Lipídeos/química , Nanopartículas/química , Tacrolimo/farmacologia , Temperatura Ambiente , Administração Cutânea , Animais , Varredura Diferencial de Calorimetria , Derme/efeitos dos fármacos , Liberação Controlada de Fármacos , Irritantes/toxicidade , Nanopartículas/ultraestrutura , Tamanho da Partícula , Coelhos , Ratos Sprague-Dawley , Absorção Cutânea/efeitos dos fármacos , Testes Cutâneos , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/química , Difração de Raios X
19.
Int J Nanomedicine ; 14: 5415-5434, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409996

RESUMO

Over the past two decades, nano-sized biosystems have increasingly been utilized to deliver various pharmaceutical agents to a specific region, organ or tissue for controllable precision therapy. Whether solid nanohydrogel, nanosphere, nanoparticle, nanosheet, micelles and lipoproteins, or "hollow" nanobubble, liposome, nanocapsule, and nanovesicle, all of them can exhibit outstanding loading and releasing capability as a drug vehicle - in particular polymeric nanovesicle, a microscopic hollow sphere that encloses a water core with a thin polymer membrane. Besides excellent stability, toughness and liposome-like compatibility, polymeric nanovesicles offer considerable scope for tailoring properties by changing their chemical structure, block lengths, stimulus-responsiveness and even conjugation with biomolecules. In this review, we summarize the latest advances in stimulus-responsive polymeric nanovesicles for biomedical applications. Different functionalized polymers are in development to construct more complex multiple responsive nanovesicles in delivery systems, medical imaging, biosensors and so on.


Assuntos
Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Nanopartículas/química , Polímeros/química , Portadores de Fármacos/química , Concentração de Íons de Hidrogênio
20.
Int J Nanomedicine ; 14: 5435-5448, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409997

RESUMO

Background: Ramipril (RMP) suffers from poor aqueous solubility along with sensitivity to mechanical stress, heat, and moisture. The aim of the current study is to improve RMP solubility and stability by designing solid self-nanoemulsifying drug delivery system (S-SNEDDS) as tablet. Methods: The drug was initially incorporated in different liquid formulations (L-SNEDDS) which were evaluated by equilibrium solubility, droplet size, and zeta potential studies. The optimized formulation was solidified into S-SNEDDS powder by the adsorbent Syloid® and compressed into a self-nanoemulsifying tablet (T-SNEDDS). The optimized tablet was evaluated by drug content uniformity, hardness, friability, disintegration, and dissolution tests. Furthermore, pure RMP, optimized L-SNEDDS, and T-SNEDDS were enrolled in accelerated and long-term stability studies. Results: Among various liquid formulations, F5 L-SNEDDS [capmul MCM/transcutol/HCO-30 (25/25/50%w/w)] showed relatively high drug solubility, nano-scaled droplet size, and high negative zeta potential value. The optimized SNEDDS solidification with Syloid® at ratio (1:1) resulted in a compressible powder with an excellent flowability. The optimized tablet (T-SNEDDS) showed accepted content uniformity, hardness, friability, and disintegration time (<15 minutes). The optimized L-SNEDDS, S-SNEDDS, and T-SNEDDS showed superior enhancement of RMP dissolution compared to the pure drug. Most importantly, T-SNEDDS showed significant (P<0.05) improvement of RMP stability compared to the pure drug and L-SNEDDS in both accelerated and long-term stability studies. Conclusion: RMP-loaded T-SNEDDS offers a potential oral dosage form that provides combined improvement of RMP dissolution and chemical stability.


Assuntos
Sistemas de Liberação de Medicamentos , Emulsões/química , Nanopartículas/química , Ramipril/farmacologia , Administração Oral , Adsorção , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Dureza , Nanopartículas/ultraestrutura , Tamanho da Partícula , Controle de Qualidade , Solubilidade , Eletricidade Estática , Comprimidos/química , Fatores de Tempo , Difração de Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA