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1.
Int J Nanomedicine ; 14: 7017-7038, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564863

RESUMO

Background: Fabrication of a smart drug delivery system that could dramatically increase the efficiency of chemotherapeutic drugs and reduce the side effects is still a challenge for pharmaceutical researchers. By the emergence of nanotechnology, a huge window was opened towards this goal, and a wide type of nanocarriers were introduced for delivering the chemotherapeutic to the cancer cells, among them are cyclodextrins with the ability to host different types of hydrophobic bioactive molecules through inclusion complexation process. Aim: The aim of this study is to design and fabricate a pH-responsive theranostic nanocapsule based on cyclodextrin supramolecular nano-structure. Materials and methods: This nanostructure contains iron oxide nanoparticles in the core surrounded with three polymeric layers including polymeric ß-cyclodextrin, polyacrylic acid conjugated to sulfadiazine, and polyethylenimine functionalized with ß-cyclodextrin. Sulfadiazine is a pH-responsive hydrophobic component capable of making inclusion complex with ß-cyclodextrin available in the first and third layers. Doxorubicin, as an anti-cancer drug model, was chosen and the drug loading and release pattern were determined at normal and acidic pH. Moreover, the biocompatibility of the nanocapsule (with/without drug component) was examined using different techniques such as MTT assay, complement activation, coagulation assay, and hemolysis. Results: The results revealed the successful preparation of a spherical nanocapsule with mean size 43±1.5 nm and negatively charge of -43 mV that show 160% loading efficacy. Moreover, the nanocapsule has an on/off switching release pattern in response to pH that leads to drug released in low acidic pH. The results of the biocompatibility tests indicated that this nano drug delivery system had no effect on blood and immune components while it could affect cancer cells even at very low concentrations (0.3 µg mL-1). Conclusion: The obtained results suggest that this is a "switchable" theranostic nanocapsule with potential application as an ideal delivery system for simultaneous cancer diagnosis and therapy.


Assuntos
Nanocápsulas/química , Polietilenoimina/química , Nanomedicina Teranóstica , beta-Ciclodextrinas/química , Animais , Doxorrubicina/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Compostos Férricos/química , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Camundongos , Nanocápsulas/ultraestrutura , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Eletricidade Estática , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/química , Difração de Raios X , beta-Ciclodextrinas/síntese química
2.
Int J Mol Sci ; 20(16)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31408980

RESUMO

3,3'-Diindolylmethane (DIM) is a bioactive compound found in Cruciferous vegetables that possesses health benefits such as antioxidant, anticancer, and anti-inflammatory effects. However, hydrophobicity and photolabile limit its pharmaceutical applications. This study aims to prepare and characterize DIM-encapsulated whey protein isolate (WPI) nanoparticles mixed at different ratios of WPI and DIM using the combined heating-ultrasound method. Results showed that all the samples showed adequate physicochemical characteristics: The mean particle size of the nanoparticles could be controlled down to 96-157 nm depending on the DIM to WPI ratio used in the preparation with a low polydispersity index (<0.5), higher negative values of zeta potential (>-40 mV) as well as with greater encapsulation efficiency (>82%). Flow behavior indices showed the shear-thinning Non-Newtonian or pseudoplastic (n < 1) behavior of the nanoparticles. The thermal properties were characterized by differential scanning calorimetry (DSC), which showed that DIM was successfully entrapped in WPI nanoparticles. The secondary structure of WPI was changed after DIM incorporation; electrostatic interaction and hydrogen bonding were major facilitating forces for nanoparticles formation, confirmed by Fourier Transform Infrared Spectroscopy (FT-IR). Transmission electron microscopy (TEM) micrographs showed that all the samples had a smooth surface and spherical structure. The wall material (WPI) and encapsulation method provide effective protection to DIM against UV light and a broad range of physiologically relevant pH's (2.5, 3.5, 4.5, 5.5, and 7). In conclusion, whey protein isolate (WPI)-based nanoparticles are a promising approach to encapsulate DIM and overcome its physicochemical limitations with improved stability.


Assuntos
Anticarcinógenos/administração & dosagem , Indóis/administração & dosagem , Nanocápsulas/química , Proteínas do Soro do Leite/química , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Anticarcinógenos/química , Antioxidantes/administração & dosagem , Antioxidantes/química , Brassicaceae/química , Composição de Medicamentos , Estabilidade de Medicamentos , Indóis/química , Nanocápsulas/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier
3.
Molecules ; 24(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340486

RESUMO

Polyurea (PU) nano-capsules have received voluminous interest in various fields due to their biocompatibility, high mechanical properties, and surface functionality. By incorporating magnetic nanoparticle (MNPs) into the polyurea system, the attributes of both PU and MNPs can be combined. In this work, we describe a facile and quick method for preparing magnetic polyurea nano-capsules. Encapsulation of ionic liquid-modified magnetite nanoparticles (MNPs), with polyurea nano-capsules (PU NCs) having an average size of 5-20 nm was carried out through interfacial polycondensation between amine and isocyanate monomers in inverse nano-emulsion (water-in-oil). The desired magnetic PU NCs were obtained utilizing toluene and triple-distilled water as continuous and dispersed phases respectively, polymeric non-ionic surfactant cetyl polyethyleneglycol/polypropyleneglycol-10/1 dimethicone (ABIL EM 90), diethylenetriamine, ethylenediamine diphenylmethane-4,4'-diisocyanate, and various percentages of the ionic liquid-modified MNPs. High loading of the ionic liquid-modified MNPs up to 11 wt% with respect to the dispersed aqueous phase was encapsulated. The magnetic PU NCs were probed using various analytical instruments including electron microscopy, infrared spectroscopy, X-ray diffraction, and nuclear magnetic spectroscopy. This unequivocally manifested the successful synthesis of core-shell polyurea nano-capsules even without utilizing osmotic pressure agents, and confirmed the presence of high loading of MNPs in the core.


Assuntos
Composição de Medicamentos/métodos , Nanopartículas de Magnetita/química , Nanocápsulas/química , Polímeros/química , DEET/química , Emulsões , Isocianatos/química , Nanopartículas de Magnetita/ultraestrutura , Nanocápsulas/ultraestrutura , Tamanho da Partícula , Poliaminas/química , Polimerização , Tolueno/química , Compostos de Trimetilsilil/química
4.
Colloids Surf B Biointerfaces ; 182: 110366, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31351273

RESUMO

Targeted delivery of vitamins to a desirable area is an active branch in a modern pharmacology. The most important and difficult delivery of vitamin B12 is that to bone marrow and nerve cells. Herein we present a first step towards the development of two types of smart carriers, polymer capsules and lyotropic liquid-crystalline nanosystems, for vitamin B12 targeted delivery and induced release. A vitamin B12 encapsulation technique into nanoengineered polymeric capsules produced by layer-by-layer assembling of polymeric shells on CaCO3 templates has been developed. The effectiveness of the process was demonstrated by optical absorption spectroscopy, transmission electron microscopy (TEM), atomic force microscopy (AFM) and small-angle X-ray diffraction. TEM and AFM analyses performed on capsules after their drying, confirmed the presence of the vitamin B12 inside the capsules in the form of crystalline nanoaggregates, 50-300 nm in diameter. Soft lipid nanovectors consisting of amphiphilic phytantriol molecules, which in water excess spontaneously self-assembly in 3D well-ordered inverse bicontinuous cubic bulk phase, were used as alternative carriers for vitamin B12. It was shown that about 30% of the vitamin added in the preparation of the soft lipid system was actually encapsulated in cubosomes and that no structural changes occurred upon loading. The Vitamin stabilizes the lipid system playing the role of its structure-forming element. The biocompatible nature, the stability and the feasibility of these systems make them good candidates as carriers for hydrophilic vitamins.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Álcoois Graxos/química , Nanocápsulas/química , Poloxâmero/química , Vitamina B 12/química , Carbonato de Cálcio/química , Cristalização , Composição de Medicamentos/métodos , Humanos , Nanocápsulas/ultraestrutura
5.
Int J Nanomedicine ; 14: 3361-3373, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190797

RESUMO

Purpose: To fabricate multifunctional nanocapsule via Pickering emulsion route to facilitate tumor-targeted delivery. Methods: Poly(N-isopropylacrylamide-co-acrylic acid) nanoparticles (PNA) stabilized nanocapsules were fabricated by Pickering emulsion (PE) technology. For controllable drug-release and enhancing targeted antitumor effects, the nanocapsules were crosslinked with cystamine and coupled on cell-surface molecule markers (cRGDfK) to achieve on-demand drug release and targeted delivery. Results: The fabricated PE and nanocapsules with average particle sizes (250 and 150 nm) were obtained. Encapsulation efficiency of hydrophobic anticancer drug (DOX) was determined as >90%. Release kinetic profiles for encapsulated nanocapsules displayed circulation stability and redox-sensitive releasing behavior with the supposed increase bioavailability. Both cytotoxicity assay, cellular uptake analysis and anticancer efficacy in B16F10 murine model demonstrated these redox-responsive drug-release and active targeted delivery. Conclusion: The results clearly demonstrated nanocapsule via PE route as promising candidate to provide an effective platform for incorporating hydrophobic drug for targeted cancer chemotherapy.


Assuntos
Sistemas de Liberação de Medicamentos , Emulsões/química , Nanocápsulas/química , Neoplasias/tratamento farmacológico , Peptídeos Cíclicos/química , Resinas Acrílicas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Morte Celular , Reagentes para Ligações Cruzadas/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Feminino , Células HeLa , Humanos , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Nanocápsulas/ultraestrutura , Oxirredução , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoimina/química
6.
Nat Commun ; 10(1): 2223, 2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-31110174

RESUMO

Mammalian cells are different from plant and microbial cells, having no exterior cell walls for protection. Environmental assaults can easily damage or destroy mammalian cells. Thus, the ability to develop a biomimetic cell wall (BCW) on their plasma membrane as a shield can advance various applications. Here we demonstrate the synthesis of BCW with a framing template and a crosslinked matrix for shielding live mammalian cells. The framing template is a supramolecular DNA structure. The crosslinked matrix is a polyelectrolyte complex made of alginate and polylysine. As the entire procedure of BCW synthesis is strictly operated under physiological conditions, BCW-covered mammalian cells can maintain high bioactivity. More importantly, the data show that BCW can shield live mammalian cells from not only physical assaults but also biological assaults. Thus, this study has successfully demonstrated the synthesis of BCW on live mammalian cells with great potential of shielding them from environmental assaults.


Assuntos
Materiais Biomiméticos/metabolismo , Parede Celular/metabolismo , DNA/metabolismo , Nanocápsulas/química , Alginatos/química , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Parede Celular/ultraestrutura , Reagentes para Ligações Cruzadas/química , Humanos , Microscopia Eletrônica de Transmissão , Nanocápsulas/ultraestrutura , Polilisina/química
7.
Colloids Surf B Biointerfaces ; 179: 128-135, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30954013

RESUMO

Most of the drug molecules are partially insoluble in aqueous solution and then may accumulate in fat tissues hampering efficient therapy. Innovative drug delivery strategies have emerged in industry or academia over the last decades, however preserving the activity of the encapsulated drug, having high drug loading capacity and controlling drug release kinetics, are still challenging. In this context, we explored the preparation of new nanocarriers, namely nanocapsules, via a templating method, and using polysaccharides exhibiting biological functions. Cationic poly(cyclodextrin) (P(CD+)) and alginate (alg-) were initially self-assembled layer-by-layer on colloidal gold nanoparticles. Removal of gold nanoparticles was then induced thorough cyanide-assisted hydrolysis, enabling the recovery of nanocapsules. A hydrophobic drug known to allow the mutation of genes inside cells, namely 4-hydroxy-tamoxifen, was loaded within the nanocapsules' shell via inclusion with the cyclodextrin cavities. The so-designed nanomaterials were incubated with immortalized podocytes to investigate i) their incorporation inside cells and ii) their efficiency for in vitro 4-hydroxy-tamoxifen-induced CreERT2 recombination. This work undoubtedly highlights a proof-of-concept for drug delivery using polysaccharides-based capsules with host properties.


Assuntos
Alginatos/química , Ciclodextrinas/química , Sistemas de Liberação de Medicamentos , Nanocápsulas/química , Podócitos/metabolismo , Tamoxifeno/farmacologia , Adsorção , Animais , Cátions , Coloides/química , Ouro/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Camundongos , Nanocápsulas/ultraestrutura , Podócitos/efeitos dos fármacos , Polieletrólitos/química , Eletricidade Estática , Água/química
8.
Exp Parasitol ; 198: 79-86, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30769018

RESUMO

Cystic echinococcosis (CE), which is caused during the metacestode larval stage of Echinococcus granulosus, is a life-threatening disease and is very difficult to treat. At present, the FDA-approved antihelmintic drugs are mebendazole (MBZ), albendazole (ABZ) and its principal metabolite ABZ sulfoxide (ABZSO), but as these have a therapeutic efficacy over 50%, underlining the need for new drug delivery systems. The aim of this work was the optimization and characterization of previously developed ABZ lipid nanocapsules (ABZ-LNCs) and evaluate their efficacy in mice infected with E. granulosus. LNCs were prepared by the phase inversion technique and characterized in terms of size, surface charge, drug loading, and in vitro stability followed by an in vivo proof-of-concept using a murine model infected with E. granulosus. Stable particle dispersions with a narrow size distribution and high efficiency of encapsulation (≥90%) were obtained. ABZ-LNCs showed a greater chemoprophylactic efficacy than ABZ suspension administered by the oral route as 4 out of the 10 ABZ-LNCs treated mice did not develop any cysts, whereas the infection progressed in all mice from the ABZ suspension group. Regarding the ultrastructural studies of cysts, mice treated with ABZ-LNCs or ABZ suspension revealed changes in the germinal layer. However, the extent of the damage appeared to be greater after ABZ-LNC administration compared to the suspension treatment. These results suggest that ABZ-LNCs could be a promising novel candidate for ABZ delivery to treat CE.


Assuntos
Albendazol/uso terapêutico , Anticestoides/uso terapêutico , Equinococose/tratamento farmacológico , Echinococcus granulosus/efeitos dos fármacos , Albendazol/administração & dosagem , Albendazol/química , Animais , Anticestoides/administração & dosagem , Anticestoides/química , Bovinos , Cromatografia Líquida de Alta Pressão , Equinococose/prevenção & controle , Echinococcus granulosus/ultraestrutura , Feminino , Intestinos/química , Camundongos , Microscopia Eletrônica de Varredura , Nanocápsulas/normas , Nanocápsulas/ultraestrutura , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/prevenção & controle , Tamanho da Partícula , Pós , Estômago/química
9.
Mater Sci Eng C Mater Biol Appl ; 94: 694-702, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30423756

RESUMO

Cilostazol (CLZ) acts as a vasodilator and antiplatelet agent and is the main drug for the treatment of intermittent claudication (IC) related to peripheral arterial disease (PAD). The usual oral dose is 100 mg twice a day, which represents a disadvantage in treatment compliance. CLZ presents several side effects, such as headache, runny nose, and dizziness. This paper aimed to obtain novel polymeric nanocapsules prepared from poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG) blend containing CLZ. Nanocapsules showed pH values between 6.1 and 6.3, average size lower than 137 nm, low polydispersity index (<0.22) and negative zeta potential. These nanoformulations demonstrated spherical shape with smooth surface. Results achieved by X-ray diffraction (XRD) and differential scanning calorimetry (DSC) indicated drug amorphization compared to pure CLZ. Fourier-transformed infrared spectroscopy (FTIR) showed no chemical bonds between drug and polymers. Formulations presented suitable stability for physical parameters. The in vitro drug release demonstrated prolonged release with no burst effect. Drug release was controlled by both mechanisms of polymer relaxation/degradation and Fickian diffusion. Moreover, chosen CLZ-loaded nanocapsules provided an in vivo prolonged antiplatelet effect for CLZ statistically similar to aspirin. These formulations can be further used as a feasible oral drug delivery carrier for controlled release of CLZ in order to treat PAD and IC events.


Assuntos
Cilostazol/farmacologia , Nanocápsulas/química , Inibidores da Agregação de Plaquetas/farmacologia , Poliésteres/química , Polietilenoglicóis/química , Animais , Varredura Diferencial de Calorimetria , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Masculino , Nanocápsulas/ultraestrutura , Tamanho da Partícula , Agregação Plaquetária/efeitos dos fármacos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
10.
J Control Release ; 291: 157-168, 2018 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-30343137

RESUMO

Peptides represent a promising therapeutic class with the potential to alleviate many severe diseases. A key limitation of these active molecules relies on the difficulties for their efficient oral administration. The objective of this work has been the rational design of polymer nanocapsules (NCs) intended for the oral delivery of peptide drugs. For this purpose, we selected insulin glulisine as a model peptide. The polymer shell of the NCs was made of a single layer of protamine, a cationic polypeptide selected for its cell penetration properties, or a double protamine/polysialic acid (PSA) layer. Insulin glulisine-loaded protamine and protamine/PSA NCs, prepared by the solvent displacement method, exhibited a size that varied in the range of 200-400 nm and a neutral surface charge (from +8 mV to -6 mV), depending on the formulation. The stability of the encapsulated peptide was assessed using circular dichroism and an in vitro cell activity study. Colloidal stability studies were also performed in simulated intestinal media containing enzymes and the results indicated that protamine NCs were stable and able to protect insulin from the harsh intestinal environment, and that this capacity could be further enhanced with a double PSA-Protamine layer. These NCs were freeze-dried and stored at room temperature without alteration of the physicochemical properties. When the insulin-loaded protamine NCs were administered intra-intestinally to diabetic rats (12 h fasting) it resulted in a prolonged glucose reduction (60%) as compared to the control insulin solution. This work raises prospects that protamine NCs may have a potential as oral peptide delivery nanocarriers.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/análogos & derivados , Nanocápsulas/química , Protaminas/química , Ácidos Siálicos/química , Administração Oral , Animais , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Células Hep G2 , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/uso terapêutico , Masculino , Nanocápsulas/ultraestrutura , Ratos Sprague-Dawley
11.
Sci Rep ; 8(1): 13158, 2018 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-30177767

RESUMO

Clinical applications of oral protein therapy for the treatment of various chronic diseases are limited due to the harsh conditions encounter the proteins during their journey in the Gastrointestinal Tract. Although nanotechnology forms a platform for the development of oral protein formulations, obtaining physiochemically stable formulations able to deliver active proteins is still challenging because of harsh preparation conditions. This study proposes the use of poly (D, L-lactic-co-caprolactone)-based polymeric nanocapsules at different monomers' ratios for protein loading and oral delivery. All formulations had a spherical shape and nano-scale size, and lysozyme encapsulation efficiency reached 80% and significantly affected by monomers' ratio. Trehalose and physical state of lysozyme had a significant effect on its biological activity (P < 0.05). Less than 10% of the protein was released in simulated gastric fluid, and 73% was the highest recorded accumulative release percentage in simulated intestinal fluid (SIF) over 24 h. The higher caprolactone content, the higher encapsulation efficiency (EE) and the lower SIF release recorded. Therefore, the formulation factors were optimised and the obtained system was PEGylated wisely to attain EE 80%, 81% SIF release within 24 h, and 98% lysozyme biological activity. The optimum formulation was prepared to deliver DNase, and similar attributes were obtained.


Assuntos
Desoxirribonuclease I/química , Sistemas de Liberação de Medicamentos , Muramidase/química , Nanocápsulas/química , Poliésteres/química , Administração Oral , Animais , Materiais Biomiméticos/química , Bovinos , Galinhas , Desoxirribonuclease I/metabolismo , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Análise Fatorial , Suco Gástrico/química , Cinética , Muramidase/metabolismo , Nanocápsulas/ultraestrutura , Tamanho da Partícula
12.
Colloids Surf B Biointerfaces ; 172: 471-479, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30199764

RESUMO

This study aimed to obtain bioactive nanosystems by combining cellulose acetate with three selected essential oils (EOs) to create spherical nanocapsules (NCs) using the solvent/anti-solvent technique. The biological activity of the obtained NCs was promoted by the use of some antimicrobial EOs: Peppermint, Cinnamon and lemongrass which were grafted on the cellulose acetate molecules. Due to their chemistry, such as long hydrocarbon tails and heads with functional groups these EOs were playing also the role of surfactant-like substance facilitating the formation of NCs. A dispersion of NCs was obtained in water and various spectroscopy techniques used to examine their size, morphology and chemistry. Dynamic light scattering calculate the size of the NCs whereas scanning electron microscopy showed their morphology. Fluorescent microscopy and Raman spectroscopy proved the attachment of the EOs in the cellulose acetate molecules. The antimicrobial activity of the obtained nanomaterials was tested against four microbial strains (bacteria: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and a yeast strain of Candida albicans). The obtained results demonstrated that such NCs can be used in a variety of applications including medical, pharmaceutical recipients and in household products for treating or preventing microbial colonization and biofilm development.


Assuntos
Anti-Infecciosos/farmacologia , Tecnologia Biomédica , Celulose/análogos & derivados , Nanocápsulas/química , Óleos Voláteis/química , Celulose/química , Difusão Dinâmica da Luz , Humanos , Testes de Sensibilidade Microbiana , Microscopia de Fluorescência , Nanocápsulas/ultraestrutura , Espectrofotometria Ultravioleta , Análise Espectral Raman , Eletricidade Estática
13.
Mater Sci Eng C Mater Biol Appl ; 91: 859-867, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30033321

RESUMO

In the present work, lipid nanocapsules (LNC) for curcumin (CCM) encapsulation have been developed and optimized. The objective was to increase drug cytotoxicity on 9L glioma cells and drug bioavailability following intravenous administration (IV). Using the phase inversion technique, we obtained 50 nm LNC loaded with CCM (4 and 6 mg/mL) and, due to the hydrophobic nature of the drug, the encapsulation efficiency was very high, being around 90%. Following 48 h of incubation with 9L cells, CCM-loaded LNC were able to reduce the viability of glioma cells resulting in significant twofold lower IC50 in comparison with the free drug solution. Moreover, CCM-loaded LNC induced both the apoptosis of 9L cells and a strong release of ATP. This suggests a cellular uptake of the LNC and an enhanced anti-proliferative effect. In order to evaluate any alteration in the pharmacokinetic behavior of the encapsulated drug, CCM-loaded LNC were injected IV into healthy rats, at a dose of 10 mg/kg. CCM pharmacokinetic studies were carried out quantifying the CCM concentration from the blood of rats, receiving either CCM-loaded LNC or free CCM solution as a control. The results demonstrated that loaded LNC exhibited a significantly higher AUC, Cmax and t1/2 in comparison with the control, while the clearance was strongly reduced. Globally, these results encouraged the use of CCM-loaded LNC to enhance the in vivo therapeutic activity of the drug after systemic administration.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Curcumina/farmacologia , Curcumina/farmacocinética , Lipídeos/química , Nanocápsulas/química , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Nanocápsulas/ultraestrutura , Tamanho da Partícula , Ratos Endogâmicos F344
14.
Molecules ; 23(7)2018 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-29937532

RESUMO

The primary objective of this study is the synthesis of nanocapsules (NC) that allow the reduction of the adsorption process of surfactant over the porous media in enhanced oil recovery processes. Nanocapsules were synthesized through the nanoprecipitation method by encapsulating commercial surfactants Span 20 and Petro 50, and using type II resins isolated from vacuum residue as a shell. The NC were characterized using dynamic light scattering, transmission electron microscopy, Fourier transform infrared, solvency tests, softening point measurements and entrapment efficiency. The obtained NC showed spherical geometry with sizes of 71 and 120 nm for encapsulated Span 20 (NCS20), and Petro 50 surfactant (NCP50), respectively. Also, the NCS20 is composed of 90% of surfactant and 10% of type II resins, while the NCP50 material is 94% of surfactant and 6% of the shell. Nanofluids of nanocapsules dispersed in deionized water were prepared for evaluating the nanofluid­sandstone interaction from adsorption phenomena using a batch-mode method, contact angle measurements, and FTIR analysis. The results showed that NC adsorption was null at the different conditions of temperatures evaluated of 25, 50, and 70 °C, and stirring velocities up to 10,000 rpm. IFT measurements showed a reduction from 18 to 1.62 and 0.15 mN/m for the nanofluids with 10 mg/L of NCS20, and NCP50 materials, respectively. Displacements tests were conducted using a 20 °API crude oil in a quarter five-spot pattern micromodel and showed an additional oil recovery of 23% in comparison with that of waterflooding, with fewer pore volumes injected than when using a dissolved surfactant.


Assuntos
Óleos Industriais/análise , Nanocápsulas/química , Campos de Petróleo e Gás , Resinas Sintéticas/química , Tensoativos/química , Adsorção , Composição de Medicamentos/métodos , Humanos , Teste de Materiais , Nanocápsulas/ultraestrutura , Porosidade , Extração em Fase Sólida/instrumentação , Extração em Fase Sólida/métodos , Temperatura Ambiente , Água/química
15.
Methods Mol Biol ; 1798: 57-67, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29868951

RESUMO

The controlled self-assembly of protein cages is vital for the use of these nanocompartments in biomedical and nanotechnological applications. Recently, we showed that by combining different structural peptide elements, it is possible to assemble viral capsid proteins in distinct well-defined morphologies. In this chapter, a triblock copolypeptide is discussed, consisting of a metal ion-coordinating hexahistidine tag, a stimulus-responsive elastin-like polypeptide and a pH-responsive self-assembling viral capsid protein. This protein is able to form two different types of capsids, depending on the assembly pathway that is followed. Here, we focus on the metal ion-induced assembly process and describe the relevant experimental procedures to induce and utilize this assembly behavior.


Assuntos
Bromovirus , Proteínas do Capsídeo , Capsídeo , Íons , Metais , Nanocápsulas , Bromovirus/fisiologia , Capsídeo/química , Capsídeo/metabolismo , Capsídeo/ultraestrutura , Proteínas do Capsídeo/química , Proteínas do Capsídeo/isolamento & purificação , Proteínas do Capsídeo/metabolismo , Íons/química , Metais/química , Modelos Moleculares , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Conformação Proteica , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Análise Espectral , Vírion/ultraestrutura , Montagem de Vírus
16.
Methods Mol Biol ; 1798: 69-83, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29868952

RESUMO

In cellular systems, compartmentalization plays an important role in the protection and regulation of enzymes. Controlled encapsulation of enzymes in nanocompartments is crucial in understanding biocatalytic processes in the cellular environment. We have recently described an enzymatic method to covalently attach enzymes, equipped with a small recognition peptide, to the interior of viral capsids. Viral capsids are especially interesting in this respect, as they form very well-defined nanoparticles with a uniform size and shape. Here, we describe the relevant experimental procedures to encapsulate a model enzyme into the interior of a viral capsid, purify the resulting viral capsids, and measure the catalytic activity of the encapsulated enzymes.


Assuntos
Bromovirus , Proteínas do Capsídeo , Capsídeo , Enzimas Imobilizadas , Nanocápsulas , Aminoaciltransferases/química , Aminoaciltransferases/genética , Aminoaciltransferases/isolamento & purificação , Aminoaciltransferases/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Proteínas de Bactérias/metabolismo , Capsídeo/química , Capsídeo/metabolismo , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/isolamento & purificação , Proteínas do Capsídeo/metabolismo , Cromatografia de Afinidade , Cisteína Endopeptidases/química , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/isolamento & purificação , Cisteína Endopeptidases/metabolismo , Enzimas Imobilizadas/química , Expressão Gênica , Concentração de Íons de Hidrogênio , Espectrometria de Massas , Modelos Moleculares , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Conformação Proteica , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Montagem de Vírus
17.
Methods Mol Biol ; 1798: 85-93, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29868953

RESUMO

Virus-like particles (VLPs) resemble viruses, but are devoid their genetic material, rendering them as noninfectious, hollow protein shells. VLPs are ideal templates to synthesize nanoparticles because they have homogeneous size and their empty cavity can provide a confined environment for selectively directed synthesis. Atom-transfer radical polymerization (ATRP) is well suited for directed synthesis of polymers inside VLPs. In addition to being rapid, monomer-promiscuous, and resulting in products with relatively low polydispersity, the simplicity of the ATRP initiator allows it to be readily modified for amending to biomolecules. This chapter describes the polymerization of 2-aminoethyl methacrylate (AEMA) via ATRP in a viral capsid derived from the bacteriophage P22.


Assuntos
Bacteriófago P22 , Proteínas do Capsídeo , Capsídeo , Nanocápsulas , Bacteriófago P22/química , Bacteriófago P22/metabolismo , Bacteriófago P22/ultraestrutura , Capsídeo/química , Capsídeo/metabolismo , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Reagentes para Ligações Cruzadas , Expressão Gênica , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Multimerização Proteica , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Montagem de Vírus
18.
Bioconjug Chem ; 29(5): 1505-1509, 2018 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-29688702

RESUMO

Vesicle-shaped supramolecular polymers are formed by self-assembly of a DNA duplex containing phenanthrene overhangs at both ends. In the presence of spermine, the phenanthrene overhangs act as sticky ends linking the DNA duplexes together. In aqueous solution, the assembly leads to vesicles with a diameter in the range of 50-200 nm. Fluorescence measurements show that the assembled phenanthrene units act as light-harvesting complexes and transfer absorbed energy to an acceptor, such as pyrene or Cy3, which can either be directly added to the polymer or attached via a complementary DNA strand. The presence of DNA in the nanostructures allows the construction of light-harvesting vesicles that are amenable to derivatization with different functional groups.


Assuntos
Carbocianinas/química , DNA/química , Transferência de Energia , Luz , Nanocápsulas/química , Fenantrenos/química , Pirenos/química , Sequência de Bases , Modelos Moleculares , Nanocápsulas/ultraestrutura
19.
ACS Nano ; 12(3): 2846-2857, 2018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29489325

RESUMO

The physicochemical properties of nanoparticles (size, charge, and surface chemistry, etc.) influence their biological functions often in complex and poorly understood ways. This complexity is compounded when the nanostructures involved have variable mechanical properties. Here, we report the synthesis of liquid-filled silica nanocapsules (SNCs, ∼ 150 nm) having a wide range of stiffness (with Young's moduli ranging from 704 kPa to 9.7 GPa). We demonstrate a complex trade-off between nanoparticle stiffness and the efficiencies of both immune evasion and passive/active tumor targeting. Soft SNCs showed 3 times less uptake by macrophages than stiff SNCs, while the uptake of PEGylated SNCs by cancer cells was independent of stiffness. In addition, the functionalization of stiff SNCs with folic acid significantly enhanced their receptor-mediated cellular uptake, whereas little improvement for the soft SNCs was conferred. Further in vivo experiments confirmed these findings and demonstrated the critical role of nanoparticle mechanical properties in regulating their interactions with biological systems.


Assuntos
Sistemas de Liberação de Medicamentos , Ácido Fólico/metabolismo , Nanocápsulas/química , Neoplasias/metabolismo , Peptídeos/metabolismo , Dióxido de Silício/metabolismo , Animais , Linhagem Celular Tumoral , Módulo de Elasticidade , Ácido Fólico/química , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Nanocápsulas/ultraestrutura , Peptídeos/química , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo , Dióxido de Silício/química , Propriedades de Superfície
20.
Colloids Surf B Biointerfaces ; 165: 103-110, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29471218

RESUMO

Liquid lipid nanocapsules (LLN) represent a promising new generation of drug-delivery systems. They can carry hydrophobic drugs in their oily core, but the composition and structure of the surrounding protective shell determine their capacity to survive in the circulatory system and to achieve their goal: penetrate tumor cells. Here, we present a study of LLN covered by the protein human serum albumin (HSA) and loaded with curcumin as a hydrophobic model drug. A cross-linking procedure was performed to further strengthen the protective protein layer. Physicochemical properties and release kinetics of the nanocapsules were investigated, and cellular uptake and killing capacity were evaluated on the human breast-cancer line MCF-7. The nanocapsules exhibited a half maximal inhibitory concentration (IC50) capacity similar to that of free curcumin, but avoiding problems associated with excipients, and displayed an outstanding uptake performance, entering cells massively in less than 1 min.


Assuntos
Neoplasias da Mama/metabolismo , Endocitose , Lipídeos/química , Nanocápsulas/química , Albumina Sérica/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/química , Curcumina/farmacologia , Curcumina/uso terapêutico , Liberação Controlada de Fármacos , Feminino , Humanos , Células MCF-7 , Nanocápsulas/ultraestrutura , Tiazóis/química
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