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1.
PLoS One ; 15(9): e0238823, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970684

RESUMO

Mucoadhesive polymeric nanocapsules have attracted interest of researchers from different fields from natural sciences because of their ability to interact with the mucosa and increase drug permeation. Anesthesia by immersion causes absorption through the skin and gills of fish, so it is important to evaluate the exposure of these organs to drug nanosystems. Benzocaine (BENZ) is one of the most popular anesthetic agents used in fish anesthesia, but it has drawbacks because of its low bioavailability, resulting in weak absorption after immersion. Here we describe method developed for preparing and characterizing chitosan-coated PLGA mucoadhesive nanoparticles containing BENZ (NPMAs) for zebrafish immersion anesthesia. We determined the lowest effective concentration, characterized the interaction of the mucoadhesive system with fish, measured the anesthetic efficacy, and evaluated possible toxic effects in embryos and adults exposed to the nanoformulations. This study opens perspectives for using nanoformulations prepared with BENZ in aquaculture, allowing reduction of dosage as well as promoting more effective anesthesia and improved interaction with the mucoadhesive system of fish.


Assuntos
Anestesia/veterinária , Benzocaína/administração & dosagem , Nanocápsulas/administração & dosagem , Peixe-Zebra , Animais , Aquicultura , Quitosana/administração & dosagem , Quitosana/toxicidade , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Brânquias/efeitos dos fármacos , Nanocápsulas/toxicidade , Pele/efeitos dos fármacos
2.
Pharm Res ; 37(10): 195, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32944793

RESUMO

PURPOSE: Design imiquimod-loaded chitosan nanocapsules for transdermal delivery and evaluate the depth of imiquimod transdermal absorption as well as the kinetics of this absorption using Raman Microscopy, an innovative strategy to evaluate transdermal absorption. This nanovehicle included Compritol 888ATO®, a novel excipient for formulating nanosystems whose administration through the skin has not been studied until now. METHODS: Nanocapsules were made by solvent displacement method and their physicochemical properties was measured by DLS and laser-Doppler. For transdermal experiments, newborn pig skin was used. The Raman spectra were obtained using a laser excitation source at 532 nm and a 20/50X oil immersion objective. RESULTS: The designed nanocapsules, presented nanometric size (180 nm), a polydispersity index <0.2 and a zeta potential +17. The controlled release effect of Compritol was observed, with the finding that half of the drug was released at 24 h in comparison with control (p < 0.05). It was verified through Raman microscopy that imiquimod transdermal penetration is dynamic, the nanocapsules take around 50 min to penetrate the stratum corneum and 24 h after transdermal administration, the drug was in the inner layers of the skin. CONCLUSIONS: This study demonstrated the utility of Raman Microscopy to evaluate the drugs transdermal penetration of in the different layers of the skin. Graphical Abstract New imiquimod nanocapsules: evaluation of their skin absorption by Raman Microscopy and effect of the compritol 888ATO® in the imiquimod release profile.


Assuntos
Quitosana/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Ácidos Graxos/farmacocinética , Imiquimode/farmacocinética , Nanocápsulas/administração & dosagem , Pele/metabolismo , Administração Cutânea , Animais , Quitosana/administração & dosagem , Quitosana/química , Ácidos Graxos/administração & dosagem , Ácidos Graxos/química , Imiquimode/administração & dosagem , Imiquimode/química , Nanocápsulas/química , Microscopia Óptica não Linear/métodos , Absorção Cutânea , Suínos
3.
Int J Nanomedicine ; 15: 6069-6084, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884263

RESUMO

Introduction: Adoptive T-cell immunotherapy emerged as a powerful and promising cancer therapy, as the problem regarding the immuno-reaction between different donors and recipients can be avoided. However, this approach is challenging. After long cultivation and expansion under laboratory media conditions, T-cells are losing their viability and function due to immune checkpoint proteins, leading to decreased efficiency in killing cancer cells. Therefore, a new strategy to improve T-cell survival and function is needed. With the advantages of nanotechnology and the biocompatibility of silica-based material, silica nanocapsules (SiNCs) provide an ideal delivery system to transport therapeutic biomolecules to T-cells. Up to now, there is a lack of cellular uptake studies of nanocarriers towards T-cells. Methods: We systematically studied the influence of various physicochemical properties such as sizes, core hydrophobicities, surface charges, and surface functionalities of SiNC for their impact on cellular uptake and toxicity in CD8+ T-cells by flow cytometry and confocal laser scanning microscopy. Cytokine secretion assay was performed using the enzyme-linked immunosorbent assay. To identify suitable uptake conditions for SiNCs into CD8+ T-cells, the impact of human serum in cell culture medium was also investigated. Results: The major impact on cellular uptake and toxicity was found to be size- and dose-dependent. Smaller sizes of SiNCs than 100 nm caused significant toxicity to the cells. It was found that the formed protein corona reduced the toxicity of the SiNCs. However, it also inhibited their uptake. Conclusion: Overall, we present a set of different criteria for a suitable design of nanocarriers and cell culture conditions, which need to be carefully considered for T-cell immunotherapy in vitro to facilitate uptake while avoiding toxicity.


Assuntos
Linfócitos T CD8-Positivos/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Portadores de Fármacos/administração & dosagem , Eletroforese em Gel de Poliacrilamida , Citometria de Fluxo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Microscopia Confocal , Coroa de Proteína/química , Dióxido de Silício/química
4.
Int J Nanomedicine ; 15: 5433-5443, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801698

RESUMO

Background: Human epidermal growth factor receptor2 (Her2) positive breast cancer represents 25% of breast cancer cases. Targeted therapy with Her2 monoclonal antibody, trastuzumab (TZ), represents the first-line treatment for this type of breast cancer. In addition, neratinib, an irreversible inhibitor of the HER-2 receptor tyrosine kinase, has recently been approved as adjuvant therapy to TZ. This study aims to formulate (TZ)-grafted dendrimers loaded with neratinib, allowing a dual treatment alongside reducing the associated resistance as well as targeted therapy. Methods: TZ was conjugated on the surface of dendrimer using hetero-cross linker, MAL-PEG-NHS, and the zeta potential, and in vitro release of neratinib from dendrimers was characterized. Formulated dendrimers were also fluorescently conjugated with fluorescein isothiocyanate to visualize and quantify their SKBR-3 cellular uptake. Results: The G4 PAMAM dendrimer showed successful encapsulation of neratinib and a sustained release profile. Comparative in vitro studies revealed that these TZ-targeted dendrimers loaded with neratinib were more selective and have higher antiproliferation activity against SKBR-3 cells compared to neratinib alone and neratinib loaded dendrimer. Conclusion: In the current study, neratinib loaded in plain and trastuzumab-grafted dendrimer were successfully prepared. Enhanced cellular uptake of trastuzumab conjugated dendrimers was shown, together with a higher cytotoxic effect than plain neratinib dendrimers. These findings suggest the potential of TZ-conjugated dendrimers as targeting carrier for cytotoxic drugs, including neratinib.


Assuntos
Dendrímeros/química , Nanocápsulas/administração & dosagem , Nylons/química , Quinolinas/química , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Dendrímeros/administração & dosagem , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Fluoresceína-5-Isotiocianato , Humanos , Terapia de Alvo Molecular/métodos , Nanocápsulas/química , Poliaminas/química , Quinolinas/administração & dosagem , Quinolinas/farmacocinética , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/administração & dosagem , Trastuzumab/química , Trastuzumab/farmacocinética
5.
Adv Exp Med Biol ; 1257: 155-168, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483738

RESUMO

Interleukin(IL)-12 is a protein that activates T cells and macrophages to kill tumor cells. However, despite this cytokine showing strong antitumor activity in preclinical settings, translation to patients has been slowed by toxic side effects, poor distribution to peripheral tissues, and improper dosing regimens. Osteosarcoma (OS) is an aggressive primary tumor of bone that has shown particular responsiveness to recombinant (r)IL-12 in preclinical models. Poly(lactic-co-glycolic) acid (PLGA) nanospheres, an FDA-approved drug delivery vector, may be a viable delivery vector for transporting biologically active IL-12 to tissues without disturbing normal homeostasis. In this chapter, we explore the potential for using IL-12-loaded nanospheres (IL-12-NS, <1 µm in diameter) to treat cancer, describe the synthesis process, and examine a typical protein release profile while providing insight and future directions of nanoscale tumor immunotherapeutics.


Assuntos
Neoplasias Ósseas , Imunoterapia , Interleucina-12 , Nanocápsulas , Osteossarcoma , Neoplasias Ósseas/terapia , Humanos , Imunoterapia/tendências , Interleucina-12/administração & dosagem , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Osteossarcoma/terapia
6.
J Neuroimmunol ; 345: 577270, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32480241

RESUMO

The purpose of current study was to evaluate the effect of curcumin (CUR) loaded lipid-core nanocapsules (CUR-LNC) treatment on neuroinflammatory and behavioral alterations in a model of sickness behavior induced by lipopolysaccharide (LPS) in rats. Rats were treated with CUR-LNC and CUR daily for 14 days. After the last treatments, sickness behavior was induced with LPS. Sickness behavior LPS-induced was confirmed by behavioral tests, an increase in levels of proinflammatory cytokines, decrease in levels of IL-10, overexpression of IDO-1 and IDO-2. In conclusion, CUR-LNC treatment attenuated the neuroinflammatory and behavioral changes caused in sickness behavior model.


Assuntos
Curcumina/administração & dosagem , Comportamento de Doença/fisiologia , Mediadores da Inflamação/imunologia , Lipopolissacarídeos/toxicidade , Locomoção/fisiologia , Nanocápsulas/administração & dosagem , Animais , Portadores de Fármacos/administração & dosagem , Comportamento de Doença/efeitos dos fármacos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Lipídeos , Locomoção/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
7.
Cir. plást. ibero-latinoam ; 46(2): 233-240, abr.-jun. 2020. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-194728

RESUMO

INTRODUCCIÓN Y OBJETIVO: La micropigmentación de cejas es un conocido procedimiento para mejorar las cejas envejecidas y las jóvenes y también para crearles una forma estética. A pesar de la evolución de la aparatología y de las rutinas para llevar a cabo este procedimiento, existe una carencia de productos que favorezcan la cicatrización y protección tanto de la piel como para el uso de nuevos pigmentos. Durante muchos años el empleo de dermocosméticos comunes con vitamina C en este procedimiento no ha estado indicado por la posibilidad de blanqueamiento y decoloración, a pesar de sus reconocidas propiedades antioxidantes y de cicatrización. En este estudio nos proponemos investigar si es posible adicionar vitamina C nanoencapsulada en el procedimiento de micropigmentación de las cejas para obtener ventaja de sus propiedades y mejorar los resultados, y si su forma nanoencapsulada puede obtener mejores resultados sin el blanqueamiento o la decoloración que parecen provocar otros dermocosméticos comunes con vitamina C. MATERIAL Y MÉTODO: Realizamos un estudio prospectivo y randomizado que incluyó 31 pacientes sometidas a micropigmentación bilateral de cejas utilizando el mismo procedimiento de rutina y el mismo aparato de micropigmentación. Bajo su consentimiento, las pacientes fueron sus propios controles y recibieron vitamina C nanoencaspulada en una ceja y rutina de micropigmentación normal en la otra. RESULTADOS: La evaluación se realizó mediante documentación fotográfica y análisis visual, valorando si hubo o no pérdida del color. La ceja derecha, tratada con vitamina C nanoencapsulada, mostró mejores resultados que el control, manteniendo los pigmentos y la forma con resultados claramente superiores (70.97%). La ceja izquierda, no tratada, mostró mejores resultados en solo el 22.58% de las pacientes. CONCLUSIONES: Los resultados fueron satisfactorios y abren una nueva visión sobre el papel de la vitamina C nanoencapsulada en la cicatrización y protección de la piel en el procedimiento de micropigmentación de las cejas


BACKGROUND AND OBJECTIVE: Eyebrows micropigmentation is a popular procedure to enhance the aged and youth eyebrows and to create an aesthetic shape to them. Despite the devices evolution and routines for this procedure there is a lack of wound healing and protection products both to skin and the new pigments. For many years, the use of regular Vitamin C dermocosmetics in this procedure has been non indicated, because the possibility of whitening and discoloration, despite its recognized wound healing and antioxidants properties. Our propose in this paper is to investigate if it's possible to add nanoencapsulated vitamin C in eyebrows micropigmentation procedure in order to take advantage of its properties, to enhance the procedure results, and if the nanoencapsulated vitamin C can get better results in eyebrows micropigmentation, without whitening and discoloration METHODS: A prospective randomized study was developed including 31 patients who underwent bilateral eyebrows micropigmentation using the same procedure routine and device. Under their consent, patients served as their own control and received nanoencapsulated vitamin C to one eyebrow and none product to the other side. RESULTS: The evaluation was carried out using photographic documentation and visual analysis, assessing whether or not there was color loss. The right eyebrow, treated with nanoencapsulated vitamin C showed better results than the control, maintaining pigments and shape with clearly superior results (70.97%). The untreated left eyebrow showed better results in only 22.58% of patients. CONCLUSIONS: The results were satisfactory and open a new vision on the role of nanoencapsulated vitamin C in the healing and protection of the skin in the micropigmentation procedure of the eyebrows


Assuntos
Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Nanocápsulas/administração & dosagem , Ácido Ascórbico/administração & dosagem , Sobrancelhas , Tatuagem/métodos , Pigmentação da Pele , Cicatriz/terapia , Procedimentos Cirúrgicos Dermatológicos/métodos , Cicatrização/efeitos dos fármacos , Estudos Prospectivos
8.
Int J Mol Sci ; 21(5)2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32151081

RESUMO

It is generally believed that antibacterial essential oils have the potential to become one of the alternatives in preventing diarrheal diseases of monogastric animals. The disadvantage is their low efficiency per oral due to easy degradation during digestion in the stomach. This study compares the efficacy of chitosan, alginate-chitosan, guar gum-chitosan, xanthan gum-chitosan and pectin-chitosan nanocapsules to the synthesis of pH-responsive biopolymeric nanocapsule for Thymus vulgaris, Rosmarinus officinalis and Syzygium aromaticum essential oils. Using spectrophotometric approach and gas chromatography, release kinetics were determined in pH 3, 5.6 and 7.4. The growth rates of S. aureus and E. coli, as well as minimal inhibition concentration of essential oils were studied. The average encapsulation efficiency was 60%, and the loading efficiency was 70%. The size of the nanocapsules ranged from 100 nm to 500 nm. Results showed that chitosan-guar gum and chitosan-pectin nanocapsules released 30% of essential oils (EOs) at pH 3 and 80% at pH 7.4 during 3 h. Similar release kinetics were confirmed for thymol, eugenol and α-pinene. Minimal inhibition concentrations of Thymus vulgaris and Syzygium aromaticum essential oils ranged from 0.025 to 0.5%. Findings of this study suggest that the suitable pH-responsive nanocapsule for release, low toxicity and antibacterial activity is based on chitosan-guar gum structure.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Nanocápsulas/administração & dosagem , Óleos Voláteis/farmacologia , Polímeros/química , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/química , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Nanocápsulas/química , Óleos Voláteis/química , Staphylococcus aureus/crescimento & desenvolvimento
9.
Int J Nanomedicine ; 15: 1625-1642, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210557

RESUMO

Background: Honokiol (HK) is a common herbal medicine extracted from magnolia plants. Low aqueous solubility and limited bioavailability of HK have hindered its clinical application, especially for cancer treatment. Nano-drug delivery system has the potential to enhance HK delivery and therefore, enhance its anti-cancer activity. Purpose: The study's aim is to design novel PEGylated-PLGA polymeric nanocapsules (NCs) for HK delivery to breast tumor-bearing mice after systemic administration. Methods: Formulation of different HK-loaded NCs and their physio-chemical characterization were optimized through the use of different formulation variables. The antitumor activity of the HK-loaded NCs was investigated both in vitro using MCF-7 and EAC breast cancer cell lines and in vivo using solid Ehrlich carcinoma (SEC) breast cancer model. Results: The optimum HK-loaded NCs were prepared from 15% PEG-PLGA diblock copolymer and exhibited the lowest nano size of 125 nm, smooth spherical morphology, highest drug loading of 94% and highest cellular uptake into breast cancer cells. HK-loaded PEGylated NCs can effectively inhibit the in vitro cell growth of breast cancer cells by 80.2% and 58.1% compared to 35% and 31% with free HK in the case of MCF-7 and EAC, respectively. HK-loaded NCs inhibited SEC tumor growth by 2.3 fold significantly higher than free HK, in vivo. Conclusion: The designed drug delivery system encapsulating HK exhibited a pronounced decrease in tumor growth biomarkers meanwhile proved its safety in animals. Therefore, 15% PEGylated HK-loaded NCs may act as a promising new approach for breast cancer treatment.


Assuntos
Compostos de Bifenilo/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Lignanas/administração & dosagem , Nanocápsulas/administração & dosagem , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/patologia , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Feminino , Humanos , Células MCF-7 , Camundongos , Micelas , Nanocápsulas/química , Polietilenoglicóis/química , Poliglactina 910/química , Solubilidade , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Biomater Sci ; 8(8): 2227-2233, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32129325

RESUMO

An enveloped virus with soft and rough shells has strong penetration ability for cells. Inspired by the unique structure of virus, we successfully constructed virus-mimicking mesoporous organosilica nanocapsules (denoted as VMONs) for the first time by decorating small-sized silica nanoparticles on soft mesoporous organosilica hollow spheres. TEM and SEM images reveal that the prepared VMONs display uniform diameters (240 nm), a soft framework, a rough surface, and excellent dispersity. Quantitative nanomechanical mapping further demonstrates that the VMONs possess an extremely low Young's modulus (36 MPa) and a scraggly surface. In view of the successful construction of the virus-mimicking nanocapsules, the VMONs are further modified with human serum albumin (HSA) and Cy5.5-maleimide (Mal-Cy5.5) to investigate their cell penetration ability. Flow cytometry analysis reveals that the internalization of VMONs@HSA-Cy5.5 increases 2.74-fold compared to that of the conventional mesoporous nanosphere. Confocal laser scanning microscopy images show that the VMONs@HSA-Cy5.5 diffuses deeper for multicellular spheroids compared to both hard and soft mesoporous organosilica nanospheres. The penetration ability of the VMONs and SMONs increases 18.49 and 6.13-fold compared to that of MONs at the depth of 60 µm. Thanks to the excellent cellular penetration ability, the virus-mimicking VMONs@HSA-Cy5.5 can effectively deliver the anticancer drug doxorubicin (Dox) into drug-resistant MCF-7/ADR human breast cancer cells and significantly enhance the chemotherapeutic efficacy. Taken together, the constructed virus-mimicking organosilica nanocapsules with a soft framework and a rough surface possess strong cellular internalization and tumor penetration abilities, providing a unique and effective nanoplatform for biomedical applications.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Neoplasias Mamárias Experimentais/metabolismo , Nanocápsulas/administração & dosagem , Compostos de Organossilício/administração & dosagem , Animais , Antibióticos Antineoplásicos/farmacocinética , Transporte Biológico , Carbocianinas/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacocinética , Feminino , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Compostos de Organossilício/farmacocinética , Porosidade , Albumina Sérica Humana/administração & dosagem , Propriedades de Superfície
11.
Rev Bras Parasitol Vet ; 29(1): e013119, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049139

RESUMO

The objective of this study was to evaluate the efficacy of carvacryl acetate (CVA) and nanoencapsulated CVA (nCVA) on gastrointestinal nematodes of sheep. The CVA was nanoencapsulated with chitosan/gum arabic and the efficacy of nanoencapsulation (EE), yield, zeta potential, nanoparticle morphology and release kinetics at pH 3 and 8 were analyzed. Acute and subchronic toxicity were evaluated in rodents and reduction of egg counts in the faeces (FECRT) of sheep. The sheep were divided into four groups (n = 10): G1, 250 mg/kg CVA; G2, 250 mg/kg nCVA; G3, polymer matrix and G4: 2.5 mg/kg monepantel. EE and nCVA yield were 65% and 57%, respectively. The morphology of the nanoparticles was spherical, size (810.6±286.7 nm), zeta potential in pH 3.2 (+18.3 mV) and the 50% release of CVA at pHs 3 and 8 occurred at 200 and 10 h, respectively. nCVA showed LD50 of 2,609 mg/kg. CVA, nCVA and monepantel reduced the number of eggs per gram of faeces (epg) by 57.7%, 51.1% and 97.7%, respectively. The epg of sheep treated with CVA and nCVA did not differ from the negative control (P>0.05). Nanoencapsulation reduced the toxicity of CVA; however, nCVA and CVA presented similar results in the FECRT.


Assuntos
Anti-Helmínticos/administração & dosagem , Trato Gastrointestinal/parasitologia , Monoterpenos/administração & dosagem , Nanocápsulas/administração & dosagem , Nematoides/efeitos dos fármacos , Infecções por Nematoides/tratamento farmacológico , Doenças dos Ovinos/tratamento farmacológico , Animais , Anti-Helmínticos/toxicidade , Fezes/parasitologia , Feminino , Camundongos , Monoterpenos/toxicidade , Nanocápsulas/toxicidade , Nematoides/classificação , Nematoides/isolamento & purificação , Infecções por Nematoides/parasitologia , Contagem de Ovos de Parasitas , Testes de Sensibilidade Parasitária , Reação em Cadeia da Polimerase em Tempo Real , Roedores , Ovinos , Doenças dos Ovinos/parasitologia , Testes de Toxicidade
12.
Cell Immunol ; 349: 104042, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32061376

RESUMO

Cytotoxic T lymphocytes (CTLs) play a major role in cancer immunotherapy. A potent tumor immunotherapy may not only require activation of anti-tumor effector cells but also rely on the use of cytokines to create a controlled environment for the development of anti-tumor T cells. In this study, we fabricated a dual-target immunonanoparticle, e.g. poly(d,l-lactide-co-glycolide) nanoparticle, by loading Interleukin-12 (IL-12) and modifying with CD8 and Glypican-3 antibodies on the surface. Our results demonstrate that the fabricated targeting immunonanoparticles bind specifically to the two target cells of interest, i.e. CD8+ T cells and HepG-2 cells via the antibody-antigen interactions and form T cell-HepG-2 cell clusters, which enhances the cytotoxicity of T cells. IL-12-containing dual-target immunonanoparticles delivered IL-12 specifically to CD8+ T cells, and favored the expansion, activation and cytotoxic activity of CD8+ T lymphocytes. These results suggest that dual-target IL-12-encapsulated nanoparticles are a promising platform for cancer immunotherapy.


Assuntos
Linfócitos T CD8-Positivos/efeitos dos fármacos , Imunoterapia/métodos , Interleucina-12/administração & dosagem , Nanocápsulas/administração & dosagem , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Divisão Celular/efeitos dos fármacos , Citotoxicidade Imunológica , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Estabilidade de Medicamentos , Células Hep G2 , Humanos , Imunofenotipagem , Testes de Liberação de Interferon-gama , Interleucina-12/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Formação de Roseta , Linfócitos T Citotóxicos/imunologia
13.
Nanoscale ; 12(4): 2626-2637, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31939969

RESUMO

Immunosuppression with glucocorticoids is a common treatment for autoimmune liver diseases and after liver transplant, which is however associated with severe side-effects. Targeted delivery of glucocorticoids to inflammatory cells, e.g. liver macrophages and Kupffer cells, is a promising approach for minimizing side effects. Herein, we prepare core-shell silica nanocapsules (SiO2 NCs) via a sol-gel process confined in nanodroplets for targeted delivery of dexamethasone (DXM) for liver immunosuppressive therapy. DXM with concentrations up to 100 mg mL-1 in olive oil are encapsulated while encapsulation efficiency remains over 95% after 15 days. Internalization of NCs by non-parenchymal murine liver cells significantly reduces the release of inflammatory cytokines, indicating an effective suppression of inflammatory response of liver macrophages. Fluorescent and magnetic labeling of the NCs allows for monitoring their intracellular trafficking and biodegradation. Controlled interaction with blood proteins and good colloidal stability in blood plasma are achieved via PEGylation of the NCs. Specific proteins responsible for stealth effect, such as apolipoprotein A-I, apolipoprotein A-IV, and clusterin, are present in large amounts on the PEGylated NCs. In vivo biodistribution investigations prove an efficient accumulation of NCs in the liver, underlining the suitability of the SiO2 NCs as a dexamethasone carrier for treating inflammatory liver diseases.


Assuntos
Imunossupressão/métodos , Fígado/efeitos dos fármacos , Nanocápsulas/administração & dosagem , Dióxido de Silício/administração & dosagem , Animais , Sobrevivência Celular , Coloides , Citocinas/metabolismo , Dexametasona/administração & dosagem , Dexametasona/química , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Células HeLa , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/química , Fígado/citologia , Fígado/imunologia , Fígado/metabolismo , Camundongos , Nanocápsulas/química , Dióxido de Silício/química , Distribuição Tecidual
14.
Gut ; 69(5): 911-919, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31401561

RESUMO

OBJECTIVE: To fulfil an unmet therapeutic need for treating type 2 diabetes by developing an innovative oral drug delivery nanosystem increasing the production of glucagon-like peptide-1 (GLP-1) and the absorption of peptides into the circulation. DESIGN: We developed a nanocarrier for the oral delivery of peptides using lipid-based nanocapsules. We encapsulated the GLP-1 analogue exenatide within nanocapsules and investigated in vitro in human L-cells (NCl-H716) and murine L-cells (GLUTag cells) the ability of the nanosystem to trigger GLP-1 secretion. The therapeutic relevance of the nanosystem in vivo was tested in high-fat diet (HFD)-induced diabetic mice following acute (one administration) or chronic treatment (5 weeks) in obese and diabetic mice. RESULTS: We demonstrated that this innovative nanosystem triggers GLP-1 secretion in both human and murine cells as well as in vivo in mice. This strategy increases the endogenous secretion of GLP-1 and the oral bioavailability of the GLP-1 analogue exenatide (4% bioavailability with our nanosystem).The nanosystem synergizes its own biological effect with the encapsulated GLP-1 analogue leading to a marked improvement of glucose tolerance and insulin resistance (acute and chronic). The chronic treatment decreased diet-induced obesity, fat mass, hepatic steatosis, together with lower infiltration and recruitment of immune cell populations and inflammation. CONCLUSION: We developed a novel nanosystem compatible with human use that synergizes its own biological effect with the effects of increasing the bioavailability of a GLP-1 analogue. The effects of the formulation were comparable to the results observed for the marketed subcutaneous formulation. This nanocarrier-based strategy represents a novel promising approach for oral peptide delivery in incretin-based diabetes treatment.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Exenatida/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon/efeitos dos fármacos , Incretinas/administração & dosagem , Nanocápsulas/administração & dosagem , Administração Oral , Análise de Variância , Animais , Esquema de Medicação , Portadores de Fármacos/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Secreção de Insulina/efeitos dos fármacos , Masculino , Camundongos , Distribuição Aleatória , Resultado do Tratamento
15.
Methods Mol Biol ; 2059: 299-313, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31435929

RESUMO

The construction protocol of bio-nanocapsule (BNC)-based nanocarriers, named GL-BNC and GL-virosome, for targeted drug delivery to macrophages is described here. First, genes encoding the Streptococcus sp. protein G-derived C2 domain (binds to IgG Fc) and Finegoldia magna protein L-derived B1 domain (binds to Igκ light chain) are prepared by PCR amplification. Subsequently, the genes encoding hepatic cell-specific binding domain of hepatitis B virus envelope L protein are replaced by these PCR products. The expression plasmid for this fused gene (encoding GL-fused L protein) can be used to transform Saccharomyces cerevisiae AH22R- cells. To obtain GL-BNC, the transformed yeast cells are disrupted with glass beads, treated with heat, and then subjected to IgG affinity column chromatography followed by size exclusion column chromatography. In addition, GL-BNCs can be fused with liposomes to form GL-virosome. The targeted delivery of GL-BNC and GL-virosome to macrophages can be confirmed by in vitro phagocytosis assays using the murine macrophage cell line RAW264.7.


Assuntos
Portadores de Fármacos/química , Macrófagos/efeitos dos fármacos , Nanocápsulas/química , Saccharomyces cerevisiae/metabolismo , Proteínas do Envelope Viral/química , Animais , Cromatografia de Afinidade , Portadores de Fármacos/administração & dosagem , Firmicutes/química , Firmicutes/genética , Firmicutes/metabolismo , Lipossomos/química , Macrófagos/metabolismo , Camundongos , Microscopia Eletrônica de Transmissão , Nanocápsulas/administração & dosagem , Nanocápsulas/ultraestrutura , Fagocitose , Reação em Cadeia da Polimerase , Domínios Proteicos/genética , Células RAW 264.7 , Proteínas Recombinantes/genética , Streptococcus/química , Streptococcus/genética , Streptococcus/metabolismo , Proteínas do Envelope Viral/genética , Fluxo de Trabalho
16.
Mol Pharm ; 17(1): 145-154, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31800255

RESUMO

Cryptococcus neoformans (C. neoformans) is one of the most well-known zoonotic fungal pathogens. Cryptococcal encephalitis remains a major cause of morbidity and mortality in immunocompromised hosts. Effective and targeting killing of C. neoformans in the brain is an essential approach to prevent and treat cryptococcal encephalitis. In this study, a fluorescent polypyridyl ruthenium complex RC-7, {[phen2Ru(bpy-dinonyl)](PF6)2 (phen = 1,10-phenanthroline, bpy-dinonyl = 4,4'-dinonyl-2,2'-bipyridine)}, was screened out, which showed a highly fungicidal effect on C. neoformans. The values of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) in antifungal activities were significantly lower than fluconazole as the control. Moreover, RC-7 was prepared as a brain-targeting nanoliposome (RDP-liposome; RDP is a peptide derived from rabies virus glycoprotein) for in vivo application. The results revealed that the liposomes could accumulate in the encephalitis brain and play an antifungal role. Compared with the cryptococcal encephalitis model mice, the RDP-liposomes remarkably prolonged the survival days of the encephalitis-bearing mice from 10 days to 24 days. Here, we introduce a polypyridyl ruthenium complex that could be used as a novel antifungal agent, and this study may have a broad impact on the development of targeted delivery based on ruthenium complex-loaded liposomes for theranostics of cryptococcal encephalitis.


Assuntos
Antifúngicos/administração & dosagem , Encéfalo/efeitos dos fármacos , Criptococose/tratamento farmacológico , Cryptococcus neoformans/efeitos dos fármacos , Encefalite Infecciosa/tratamento farmacológico , Lipossomos/administração & dosagem , Nanocápsulas/administração & dosagem , Compostos de Rutênio/administração & dosagem , Animais , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/uso terapêutico , Encéfalo/microbiologia , Encéfalo/patologia , Células Cultivadas , Criptococose/microbiologia , Criptococose/mortalidade , Cryptococcus neoformans/metabolismo , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Glicoproteínas/química , Encefalite Infecciosa/microbiologia , Encefalite Infecciosa/mortalidade , Lipossomos/síntese química , Lipossomos/química , Lipossomos/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Nanocápsulas/química , Nanocápsulas/uso terapêutico , Neurônios/efeitos dos fármacos , Fragmentos de Peptídeos/química , Compostos de Rutênio/química , Compostos de Rutênio/uso terapêutico , Nanomedicina Teranóstica , Distribuição Tecidual , Proteínas Virais/química
17.
Rev. bras. parasitol. vet ; 29(1): e013119, 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1058018

RESUMO

Abstract The objective of this study was to evaluate the efficacy of carvacryl acetate (CVA) and nanoencapsulated CVA (nCVA) on gastrointestinal nematodes of sheep. The CVA was nanoencapsulated with chitosan/gum arabic and the efficacy of nanoencapsulation (EE), yield, zeta potential, nanoparticle morphology and release kinetics at pH 3 and 8 were analyzed. Acute and subchronic toxicity were evaluated in rodents and reduction of egg counts in the faeces (FECRT) of sheep. The sheep were divided into four groups (n = 10): G1, 250 mg/kg CVA; G2, 250 mg/kg nCVA; G3, polymer matrix and G4: 2.5 mg/kg monepantel. EE and nCVA yield were 65% and 57%, respectively. The morphology of the nanoparticles was spherical, size (810.6±286.7 nm), zeta potential in pH 3.2 (+18.3 mV) and the 50% release of CVA at pHs 3 and 8 occurred at 200 and 10 h, respectively. nCVA showed LD50 of 2,609 mg/kg. CVA, nCVA and monepantel reduced the number of eggs per gram of faeces (epg) by 57.7%, 51.1% and 97.7%, respectively. The epg of sheep treated with CVA and nCVA did not differ from the negative control (P>0.05). Nanoencapsulation reduced the toxicity of CVA; however, nCVA and CVA presented similar results in the FECRT.


Resumo O objetivo deste trabalho foi avaliar a eficácia do acetato de carvacrila (ACV) e do ACV nanoencapsulado (nACV) sobre nematóides gastrintestinais de ovinos. O ACV foi nanoencapsulado com quitosana/goma arábica e foi analisada a eficácia de nanoencapsulamento (EE), o rendimento, potencial zeta, morfologia das nanopartículas e cinética de liberação em pH 3 e 8. Foram avaliadas as toxicidades aguda e subcrônica em roedores e a redução da contagem de ovos nas fezes (RCOF) de ovinos. Os ovinos foram divididos em quatro grupos (n = 10): G1, 250 mg/kg ACV; G2, 250 mg/kg de nACV; G3, matriz polimérica e G4: 2,5 mg/kg de monepantel. A EE e o rendimento de nACV foram de 65% e 57%, respectivamente. A morfologia das nanopartículas foi esférica, tamanho (810,6±286,7 nm), potencial zeta no pH 3,2 (+18,3 mV) e a liberação de 50% de CVA nos pHs 3 e 8 ocorreu às 200 e 10 h, respectivamente. nACV apresentou DL50 de 2.609 mg/kg. ACV, nACV e o monepantel reduziram a contagem de ovos por grama de fezes (opg) em 57,7%, 51,1% e 97,7%, respectivamente. A contagem de opg de ovelhas tratadas com ACV e nCVA não diferiu do controle negativo (P>0,05). O nanoencapsulamento reduziu a toxicidade do AVC; no entanto, nACV e ACV apresentaram resultados semelhantes na RCOF.


Assuntos
Animais , Feminino , Doenças dos Ovinos/tratamento farmacológico , Monoterpenos/administração & dosagem , Trato Gastrointestinal/parasitologia , Nanocápsulas/administração & dosagem , Anti-Helmínticos/administração & dosagem , Nematoides/efeitos dos fármacos , Infecções por Nematoides/tratamento farmacológico , Contagem de Ovos de Parasitas , Roedores , Doenças dos Ovinos/parasitologia , Ovinos , Testes de Toxicidade , Testes de Sensibilidade Parasitária , Monoterpenos/toxicidade , Nanocápsulas/toxicidade , Fezes/parasitologia , Reação em Cadeia da Polimerase em Tempo Real , Anti-Helmínticos/toxicidade , Camundongos , Nematoides/isolamento & purificação , Nematoides/classificação , Infecções por Nematoides/parasitologia
19.
IEEE Trans Nanobioscience ; 18(4): 549-557, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31562097

RESUMO

In developing countries, the incidence of postharvest losses reduces the quantity and quality of food for human consumption and causes an economical damage along the food chain, especially, for primary producers. In this study, a multisystem coating (NC-EOt-C) based on pullulan and polymeric nanocapsules containing EO of Thymus vulgaris L. (EOt) was applied to increase the shelf life of table grapes (Vitis vinifera L.). The major components of EOt, chemically characterized by GC-MS, were o-cymene (32.68%), thymol (31.90%), and γ -terpinene (15.69%). The NC-EOt were prepared by nanoprecipitation and showed a particle mean size of 153.9 nm, a polydispersity index of 0.186, a zeta potential of -4.11 mV, and an encapsulation efficiency of 52.81%. The antioxidant capacity (DPPH and ABTS+ methods) of EOt was maintained, or even improved, after its incorporation into NC. The shelf life study showed that grapes having the NC-EOt-C multisystem maintained their characteristics of color, firmness, TA, and SSC for longer time than those without the multisystem. NC-EOt-C multisystem acted as a barrier which reduced the metabolism of fruits. In addition, the compounds of EOt with antimicrobial activity avoided microorganism growth, while those with antioxidant activity reduced the oxidative stress induced during postharvest of grapes. Additionally, the polymeric structure of NC prevented the rapid evaporation of volatile compounds of EOt, increasing then their residence time on the fruit. Our study demonstrated that NC-EOt-C multisystem can be a viable alternative to preserve horticultural products for longer storage periods.


Assuntos
Conservação de Alimentos/métodos , Frutas/efeitos dos fármacos , Glucanos/administração & dosagem , Nanocápsulas/administração & dosagem , Óleos Voláteis/administração & dosagem , Thymus (Planta) , Vitis/efeitos dos fármacos , Óleos Voláteis/química , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/análise
20.
J Food Biochem ; 43(8): e12942, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31368562

RESUMO

The main objective of this study was to evaluate whether the addition of curcumin-loaded nanocapsules (prepared and characterized) in the diets of dairy sheep improved milk quality. The nanocapsules were prepared using two polymers: poly-ε-caprolactone (PCL) and Eudragit L-100. The nanocapsules contained 0.25 mg/ml (Nano-Eudragit L-100) and 2 mg/ml (Nano-PCL) of curcumin. Dairy sheep were divided into four groups: A (control), B (30 mg free curcumin/kg concentrate), C (3 mg Nano-PCL/kg concentrate), and D (3 mg Nano-Eudragit/kg concentrate). We observed that the number of total leukocytes and serum globulin levels were lower in Group D than in the control (Group A) (p < 0.05). Antioxidant capacity against peroxyl radicals (ACAP) and catalase enzymes was elevated in Group D, with consequently reduced lipid peroxidation (LPO; p < 0.05). In milk, there were no differences in production and composition between groups during the experimental period (p > 0.05); however, ACAP increased and LPO decreased in milk. PRACTICAL APPLICATIONS: Curcumin is a functional molecule with potent antioxidant, anti-inflammatory, and antimicrobial actions, used frequently and with medical indications in human food. Free curcumin in sheep diets improves milk quality and increases its shelf life. This study showed that curcumin nanocapsules produced from the Eudragit L-100 polymer potentiated the anti-inflammatory and antioxidant actions of dairy sheep when used in the diet daily, at doses 10 times lower than that of free curcumin. These positive effects were reflected in higher total antioxidant capacity and lower lipid peroxidation in milk in sheep-fed curcumin-loaded Eudragit L-100 nanocapsules, generating desirable milk properties. In practice, the use of nanotechnology enhances the beneficial effects of curcumin in milk, possibly creating a nutraceutical food desirable to consumers.


Assuntos
Antioxidantes/metabolismo , Curcumina/administração & dosagem , Leite/química , Ovinos/metabolismo , Ração Animal/análise , Animais , Curcumina/química , Suplementos Nutricionais/análise , Composição de Medicamentos , Feminino , Armazenamento de Alimentos , Peroxidação de Lipídeos , Leite/metabolismo , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Ácidos Polimetacrílicos/química
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