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1.
Int J Nanomedicine ; 16: 1377-1390, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33658778

RESUMO

Background: Vascular drug delivery becomes a promising direction in the development of novel therapeutic strategies in the treatment of cardiovascular pathologies, such as hypertension. However, targeted delivery of hydrophobic substances, with poor bioavailability, remains a challenge. Here, we described the hypotensive effects of a low dose of curcumin delivered to the vascular wall using hyaluronic acid-based nanocapsules. Methods: The group of hypertensive TGR(m-Ren2)27 rats, was administrated respectively with the vehicle, curcumin solution or curcumin delivered using hyaluronic acid-based nanocapsules (HyC12-Cur), for 7 days each, maintaining the wash-out period between treatments. Arterial blood pressure (systolic - SBP, diastolic - DBP) and heart rate (HR) were monitored continuously using a telemetry system (Data Science International), and Mean Arterial Pressure (MAP) was calculated from SBP and DBP. Results: In hypertensive rats, a low dose of curcumin (4.5 mg/kg) administrated in HyC12-Cur for 7 days resulted in a gradual inhibition of SBP, DBP and MAP increase without an effect on HR. At the end of HyC12-Cur - based treatment changes in SBP, DBP and MAP amounted to -2.0±0.8 mmHg, -3.9±0.7 mmHg and -3.3±0.7 mmHg, respectively. In contrast, the administration of a curcumin solution (4.5 mg/kg) did not result in a significant hypotensive effect and the animals constantly developed hypertension. Vascular delivery of capsules with curcumin was confirmed using newly developed fluorine-rich nanocapsules (HyFC10-PFOB) with a shell based on a HA derivative and similar size as HyC12-Cur. HyFC10-PFOB gave fluorine signals in rat aortas analyzed ex vivo with a 19F NMR technique after a single intragastric administration. Conclusion: These results suggest that nanocapsules based on hyaluronic acid, the ubiquitous glycosaminoglycan of the extracellular matrix and an integral part of endothelial glycocalyx, may represent a suitable approach to deliver hydrophobic, poorly bioavailable compounds, to the vascular wall.


Assuntos
Curcumina/administração & dosagem , Curcumina/uso terapêutico , Ácido Hialurônico/química , Hipertensão/tratamento farmacológico , Nanocápsulas/química , Administração Oral , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Pressão Sanguínea/efeitos dos fármacos , Curcumina/farmacologia , Diástole/efeitos dos fármacos , Relação Dose-Resposta a Droga , Flúor/química , Frequência Cardíaca/efeitos dos fármacos , Hidrodinâmica , Interações Hidrofóbicas e Hidrofílicas , Hipertensão/fisiopatologia , Espectroscopia de Ressonância Magnética , Masculino , Tamanho da Partícula , Ratos , Eletricidade Estática , Sístole/efeitos dos fármacos
2.
Food Chem ; 351: 129301, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33639433

RESUMO

A major challenge in delivering curcumin effectively to the gut is its low solubility. One interesting approach to increase curcumin bioaccessibility is its emulsification. Here, we present curcumin-loaded liquid lipid nanocapsules (LLNs), obtained through olive oil emulsification, in which LLNs are coated by a protective shell composed of Bovine Serum Albumin (BSA) and hyaluronic acid (HA). Bioaccessibility of curcumin is evaluated following a standard in vitro digestion protocol. The presence of HA in the shell increases the amount of curcumin retained in the LLNs after in vitro gastric digestion from ~25% to ~85%. This protective effect occurs when HA binds to BSA in the shell. Moreover, this binding appears to be reinforced under gastric conditions, hence evidencing the crucial role of interfacial composition in protecting encapsulated curcumin. Interfacial engineering of nanoemulsions provides a route to improve the bioaccessibility of encapsulated curcumin at different stages in the gut.


Assuntos
Curcumina/farmacocinética , Digestão , Emulsões/química , Ácido Hialurônico/farmacologia , Disponibilidade Biológica , Humanos , Lipídeos , Nanocápsulas/química
3.
Int J Mol Sci ; 22(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33430158

RESUMO

(1) Background: Chiral nanoparticular systems have recently emerged as a compelling platform for investigating stereospecific behavior at the nanoscopic level. We describe chiroselective supramolecular interactions that occur between DNA oligonucleotides and chiral polyurea nanocapsules. (2) Methods: We employ interfacial polyaddition reactions between toluene 2,4-diisocyanate and lysine enantiomers that occur in volatile oil-in-water nanoemulsions to synthesize hollow, solvent-free capsules with average sizes of approximately 300 nm and neutral surface potential. (3) Results: The resultant nanocapsules exhibit chiroptical activity and interact differentially with single stranded DNA oligonucleotides despite the lack of surface charge and, thus, the absence of significant electrostatic interactions. Preferential binding of DNA on D-polyurea nanocapsules compared to their L-counterparts is demonstrated by a fourfold increase in capsule size, a 50% higher rise in the absolute value of negative zeta potential (ζ-potential), and a three times lower free DNA concentration after equilibration with the excess of DNA. (4) Conclusions: We infer that the chirality of the novel polymeric nanocapsules affects their supramolecular interactions with DNA, possibly through modification of the surface morphology. These interactions can be exploited when developing carriers for gene therapy and theranostics. The resultant constructs are expected to be highly biocompatible due to their neutral potential and biodegradability of polyurea shells.


Assuntos
DNA/química , Portadores de Fármacos/farmacologia , Nanocápsulas/química , Oligonucleotídeos/química , Aptâmeros de Nucleotídeos/química , DNA/antagonistas & inibidores , Portadores de Fármacos/química , Emulsões/química , Emulsões/farmacologia , Humanos , Oligonucleotídeos/genética , Tamanho da Partícula , Polímeros/química
4.
ACS Appl Mater Interfaces ; 13(2): 2165-2178, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33400482

RESUMO

Oxidative damage to cells from metabolites at a wound site is one of the trickiest factors inhibiting tissue regeneration, especially with bulk damage. In addition, an excessive inflammatory reaction by the body at the wound site can make it even worse. How to scavenge the reactive oxygen species (ROS) produced from metabolism and inflammatory reactions has become a critical issue in tissue engineering. Here, we utilize the natural bioactive small molecules l-arginine and l-phenylalanine and the growth factor inositol to synthesize a branched poly(ester amide) (BPEA) to fabricate BPEA nanocapsules for vitamin E delivery at wound sites. BPEA nanocapsules loaded with vitamin E (BPEA@VE NCs) could protect cells from both extracellular and intracellular damage by scavenging ROS. Simultaneously, the inflammatory reaction could also be downregulated, benefiting from the introduction of l-arginine. Furthermore, the biodegradation products of BPEA are natural metabolites of the body, such as amino acids and growth factors, guaranteeing the biocompatibility of the BPEA@VE NCs. The protective ability of the BPEA@VE NCs was also investigated in vivo for accelerated wound healing. All the results indicate that the BPEA@VE NCs have promising potential for the modulation of the local microenvironment in tissue engineering for excellent antioxidative and anti-inflammatory properties.


Assuntos
Aminoácidos/administração & dosagem , Antioxidantes/administração & dosagem , Inositol/administração & dosagem , Nanocápsulas/química , Vitamina E/administração & dosagem , Cicatrização/efeitos dos fármacos , Aminoácidos/farmacologia , Aminoácidos/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Arginina/administração & dosagem , Arginina/farmacologia , Arginina/uso terapêutico , Células Endoteliais da Veia Umbilical Humana , Humanos , Inositol/farmacologia , Inositol/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Masculino , Camundongos , Células NIH 3T3 , Fenilalanina/administração & dosagem , Fenilalanina/farmacologia , Fenilalanina/uso terapêutico , Poliésteres/química , Células RAW 264.7 , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Engenharia Tecidual , Vitamina E/farmacologia , Vitamina E/uso terapêutico
5.
J Mater Chem B ; 9(3): 783-792, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33333547

RESUMO

Pesticides play a very important role in pest control and plant protection. However, they can be limited by a tendency to cause ecological system damage due to significant losses into the environment. To increase pesticide utilization efficiency, we developed highly leaf-adhesive avermectin nanocapsules (Av-pH-cat@CS) with pH-responsive controlled release properties. The Av-pH-cat@CS nanocapsules displayed good thermal stability and photostability in response to UV light irradiation. The Av-pH-cat@CS nanocapsules could be disrupted at low pH and they exhibited excellent controlled release in response to pH, which improved the release of avermectins. In addition, the Av-pH-cat@CS nanocapsules were highly adhesive to crop leaves as a result of strong hydrogen bonding, which prolonged the retention time on crop leaves. The Av-pH-cat@CS nanocapsules with pH-responsive release and strong leaf adhesion improved the control efficacy and enhanced the utilization efficiency. Our findings offer a promising approach to prolonging pesticide duration on crop leaves and improving the utilization efficiency.


Assuntos
Adesivos/química , Antiprotozoários/química , Ivermectina/análogos & derivados , Nanocápsulas/química , Praguicidas/química , Adesivos/síntese química , Antiprotozoários/síntese química , Liberação Controlada de Fármacos , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Ivermectina/síntese química , Ivermectina/química , Estrutura Molecular , Tamanho da Partícula , Praguicidas/síntese química , Folhas de Planta/química , Propriedades de Superfície , Fatores de Tempo , Zea mays/química
6.
J Mater Chem B ; 9(3): 846-856, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33367418

RESUMO

The indiscriminate and sporadic use of antibiotics has contributed to the emergence of drug resistance phenomenon in bacteria including but not limited to Staphylococcus aureus. These drug-resistant bacteria have been threatening safety in hospitals and adversely affecting human health. Here we report a strategy to design photo-stimulated theranostic nanoprobes against methicillin-resistant Staphylococcus aureus (MRSA) "superbug" USA300. The nanocapsule probe is based on gold nanorods (GNRs) coated with pegylated thiol, mPEG-SH, which has been further modified by adding successively a natural antibacterial compound such as curcumin, and a cell targeting deoxyribonucleic acid (DNA) aptamer. We have used this novel gold nanocapsules for near-infrared (NIR) photophysical stimulation against pathogenic bacteria. We have found that the novel nanocapsule blocks biofilm formation and kills bacteria by photothermal action that causes disruption of the bacterial cell wall and membrane. In this approach, multiple drug-resistant Staphylococcus aureus has been captured by these nanocapsules through DNA aptamer targeting. All of the trapped bacteria could be killed in 30 minutes during the NIR stimulation due to the combination of photothermal effect, the generation of reactive oxygen species (ROS) and a loss of transmembrane potential (Δψ). Importantly we did not notice any resistance developed against the photothermal treatment. This is remarkable from an anti-biofilm activity point of view. Importantly, these multifunctional nanocapsules have also shown a surface enhanced Raman spectroscopy (SERS) effect, which could be used to evaluate the success of the inactivation effect during treatment. These results indicate that nanocapsule-based photo treatment can be an alternative antibacterial strategy without contributing to antibiotic resistance, and thus can be used for both environmental and therapeutic applications.


Assuntos
Antibacterianos/farmacologia , Ouro/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Nanocápsulas/química , Antibacterianos/química , Ouro/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Tamanho da Partícula , Processos Fotoquímicos , Propriedades de Superfície
7.
Methods Mol Biol ; 2208: 101-121, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32856258

RESUMO

Spherical viruses are unique nanocapsules formed by self-assembly of coat proteins (capsids). By mimicking natural spherical capsids, various artificial viral capsids are developed by using self-assembled proteins and peptides as building blocks. We developed an artificial viral capsid consisting of a ß-annulus peptide designed from natural viruses. The "ß-annulus capsid" can be functionalized by encapsulating guest molecules to the inside and decoration of exogenous molecules on the outside. Here, we describe the encapsulation and decoration on the ß-annulus capsids by connecting additional sequences to the ß-annulus peptide, conjugation with objective molecules, and subsequent self-assembly in aqueous solutions.


Assuntos
Nanocápsulas/química , Peptídeos/química , Sequência de Aminoácidos , Capsídeo/química , Proteínas do Capsídeo/química
8.
Int J Mol Sci ; 21(24)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339139

RESUMO

There are many nanoencapsulation systems available today. Among all these, mesoporous silica particles (MSPs) have received great attention in the last few years. Their large surface-to-volume ratio, biocompatibility, and versatility allow the encapsulation of a wide variety of drugs inside their pores. However, their chemical instability in biological fluids is a handicap to program the precise release of the therapeutic compounds. Taking advantage of the dissolving capacity of silica, in this study, we generate hollow capsules using MSPs as transitory sacrificial templates. We show how, upon MSP coating with different polyelectrolytes or proteins, fully customized hollow shells can be produced. These capsules are biocompatible, flexible, and biodegradable, and can be decorated with nanoparticles or carbon nanotubes to endow the systems with supplementary intrinsic properties. We also fill the capsules with a fluorescent dye to demonstrate intracellular compound release. Finally, we document how fluorescent polymeric capsules are engulfed by cells, releasing their encapsulated agent during the first 96 h. In summary, here, we describe how to assemble a highly versatile encapsulation structure based on silica mesoporous cores that are completely removed from the final polymeric capsule system. These drug encapsulation systems are highly customizable and have great versatility as they can be made using silica cores of different sizes and multiple coatings. This provides capsules with unique programmable attributes that are fully customizable according to the specific needs of each disease or target tissue for the development of nanocarriers in personalized medicine.


Assuntos
Nanocápsulas/química , Dióxido de Silício/química , Liberação Controlada de Fármacos , Corantes Fluorescentes/administração & dosagem , Células HeLa , Humanos , Polieletrólitos/química
9.
Nat Commun ; 11(1): 5448, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116131

RESUMO

Compartmentalization is a ubiquitous building principle in cells, which permits segregation of biological elements and reactions. The carboxysome is a specialized bacterial organelle that encapsulates enzymes into a virus-like protein shell and plays essential roles in photosynthetic carbon fixation. The naturally designed architecture, semi-permeability, and catalytic improvement of carboxysomes have inspired rational design and engineering of new nanomaterials to incorporate desired enzymes into the protein shell for enhanced catalytic performance. Here, we build large, intact carboxysome shells (over 90 nm in diameter) in the industrial microorganism Escherichia coli by expressing a set of carboxysome protein-encoding genes. We develop strategies for enzyme activation, shell self-assembly, and cargo encapsulation to construct a robust nanoreactor that incorporates catalytically active [FeFe]-hydrogenases and functional partners within the empty shell for the production of hydrogen. We show that shell encapsulation and the internal microenvironment of the new catalyst facilitate hydrogen production of the encapsulated oxygen-sensitive hydrogenases. The study provides insights into the assembly and formation of carboxysomes and paves the way for engineering carboxysome shell-based nanoreactors to recruit specific enzymes for diverse catalytic reactions.


Assuntos
Proteínas de Bactérias/metabolismo , Reatores Biológicos , Hidrogênio/metabolismo , Organelas/metabolismo , Proteínas de Bactérias/genética , Biocatálise , Bioengenharia , Reatores Biológicos/microbiologia , Escherichia coli/genética , Escherichia coli/metabolismo , Genes Bacterianos , Halothiobacillus/genética , Halothiobacillus/metabolismo , Hidrogenase/metabolismo , Proteínas com Ferro-Enxofre/metabolismo , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Organelas/genética , Organelas/ultraestrutura , Fotossíntese , Ribulose-Bifosfato Carboxilase/genética , Ribulose-Bifosfato Carboxilase/metabolismo
10.
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
11.
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
12.
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
13.
AAPS PharmSciTech ; 21(6): 229, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778976

RESUMO

Lung cancer is the most frequent type of cancer and the leading cause of cancer-related mortality worldwide. This study aimed to develop erlotinib (ELB)-loaded poly(ε-caprolactone) nanocapsules (NCELB) and evaluated their in vitro cytotoxicity in A549 cells. The formulation was characterized in relation to hydrodynamic diameter (171 nm), polydispersity index (0.076), zeta potential (- 8 mV), drug content (0.5 mg.mL-1), encapsulation efficiency (99%), and pH (6.0). NCELB presented higher cytotoxicity than ELB in solution against A549 cells in the MTT and LIVE/DEAD cell viability assays after 24 h of treatment. The main mechanism of cytotoxicity of NCELB was the induction of apoptosis in A549 cells. Further, a significant decrease in A549 colony formation was verified after NCELB treatment in comparison with the unencapsulated drug treatment. The reduction in clonogenic capacity is very relevant as it can reduce the risk of tumor recurrence and metastasis. In conclusion, erlotinib-loaded PCL nanocapsules are promising nanoparticles carriers to increase the efficacy of ELB in lung cancer treatment.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Poliésteres/química , Células A549 , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Cloridrato de Erlotinib/química , Cloridrato de Erlotinib/farmacologia , Humanos , Nanocápsulas/química , Nanopartículas/química
14.
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
15.
Pharm Res ; 37(6): 92, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32394200

RESUMO

PURPOSE: The aim of the study was to evaluate organogel nanoparticles as a lipophilic vehicle to increase the oral bioavailability of poorly soluble compounds. Efavirenz (EFV), a Biopharmaceutical Classification System (BCS) Class II, was used as drug model. METHODS: Organogel nanoparticles loaded with EFV were formulated with sunflower oil, 12-hydroxystearic acid (HSA) and polyvinyl alcohol (PVA). Various parameters have been investigated in the current study such as (i) the release profile of organogel assessed by USP 4 cell flow dialysis, (ii) the impact of organogel on intestinal absorption, using Caco-2 cells as in vitro model and jejunum segments as ex vivo assay and (iii) the bioavailability of organogel following oral pharmacokinetic study. RESULTS: 250-300 nm spherical particles with a final concentration of 4.75 mg/mL drug loading were obtained, corresponding to a thousand fold increase in EFV solubility, combined to a very high encapsulation efficiency (>99.8%). Due to rapid diffusion, drug was immediately released from the nanoparticles. The biopharmaceutical evaluation on ex vivo jejunum segments demonstrated an increased absorption of EFV from organogel nanoparticles compare to a native EFV suspension. In vitro assays combining Caco-2 cell cultures with TEM and confocal microscopy demonstrated passive diffusion, while paracellular integrity and endocytosis activity remain expelled. Oral pharmacokinetics of EFV organogel nanoparticles improve oral bioavailability (Fr: 249%) and quick absorption compared to EFV suspension. CONCLUSION: Organogel nanoparticles increase the bioavailability of BCS Class II drugs. The main phenomena is simply oil transfer from the gelled particles through the cell membrane.


Assuntos
Benzoxazinas/química , Portadores de Fármacos/química , Géis/química , Nanocápsulas/química , Álcool de Polivinil/química , Ácidos Esteáricos/química , Óleo de Girassol/química , Alquinos , Animais , Benzoxazinas/administração & dosagem , Benzoxazinas/farmacocinética , Disponibilidade Biológica , Células CACO-2 , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclopropanos , Difusão , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Excipientes/química , Humanos , Absorção Intestinal , Masculino , Solubilidade , Suspensões/química , Distribuição Tecidual
16.
Pharm Res ; 37(6): 91, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385723

RESUMO

PURPOSE: Bevacizumab (BCZ) is a recombinant monoclonal antibody that inhibits the biological activity of the vascular endothelial growth factor, which has an important role in angiogenesis for tumoral growth and progression. In this way, our objective was to develop chitosan-coated lipid-core nanocapsules functionalized with BCZ by an organometallic complex using gold-III. METHODS: The formulation was produced and characterized in relation to physicochemical characteristics. Furthermore, the antitumoral and antiangiogenic activities were evaluated against C6 glioma cell line and chicken embryo chorioallantoic membrane (CAM), respectively. RESULTS: Final formulation showed nanometric size, narrow polydispersity, positive zeta potential and gold clusters size lower than 2 nm. BCZ in aqueous solution (0.01-0.10 µmol L-1) did not show cytotoxic activity in vitro against C6 glioma cell line; although, MLNC-Au-BCZ showed cytotoxicity with a median inhibition concentration of 30 nmol L-1 of BCZ. Moreover, MLNC-Au-BCZ demonstrated cellular internalization dependent on incubation time and BCZ concentration. BCZ solution did not induce significant apoptosis as compared to MLNC-Au-BCZ within 24 h of treatment. CAM assay evidenced potent antiangiogenic activity for MLNC-Au-BCZ, representing a decrease of 5.6 times in BCZ dose comparing to BCZ solution. CONCLUSION: MLNC-Au-BCZ is a promising product for the treatment of solid tumors.


Assuntos
Inibidores da Angiogênese/química , Bevacizumab/química , Quitosana/química , Glioma/tratamento farmacológico , Ouro/química , Lipídeos/química , Nanocápsulas/química , Inibidores da Angiogênese/farmacologia , Animais , Apoptose/efeitos dos fármacos , Bevacizumab/metabolismo , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Composição de Medicamentos/métodos , Hexoses/química , Humanos , Lectinas de Plantas/química , Polissorbatos/química , Proteínas de Soja/química , Propriedades de Superfície , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Food Chem ; 326: 126997, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32422511

RESUMO

The increased demand for pesticide-free foods has also increased the search for healthier and environmentally friendly alternatives in agriculture. Essential oils are known to possess natural antifungal properties, becoming a reliable alternative for commercial fungicides, especially for postharvest decay control. However, essential oils are volatile and photodegradable, which reduces their long-term activities. This work presents the development of a lemongrass essential oil-containing poly(lactic acid) nanocapsules. They have shown in vitro antifungal activity against Colletotrichum acutatum and Colletotrichum gloeosporioides with a MIC dosage of 0.1% (v/v) for both phytopathogens. In the in vivo assay with postharvest apples, the ones treated with encapsulated essential oil showed bitter rot lesions three times smaller than the ones treated with non-encapsulated essential oil, or in comparison to the apples in positive control. The methodology led to stable nanocapsules with spherical morphology, a mean diameter of 96.4 nm, and with an encapsulation efficiency of 99%.


Assuntos
Antifúngicos/farmacologia , Colletotrichum/efeitos dos fármacos , Cymbopogon/química , Fungicidas Industriais/farmacologia , Nanocápsulas/química , Óleos Voláteis/química , Poliésteres/farmacologia , Malus/efeitos dos fármacos , Malus/microbiologia , Poliésteres/química
18.
Int J Nanomedicine ; 15: 1267-1281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32161457

RESUMO

Background: Joint arthroplasty has improved the quality of life of patients worldwide, but infections of the prosthesis are frequent and cause significant morbidity. Antimicrobial coatings for implants promise to prevent these infections. Methods: We have synthesized nanocapsules of titanium dioxide in amorphous or anatase form containing silver as antibacterial agent and tested their impact on bacterial growth. Furthermore, we explored the possible effect of the nanocapsules on the immune system. First, we studied their uptake into macrophages using a combination of electron microscopy and energy-dispersive spectroscopy. Second, we exposed immune cells to the nanocapsules and checked their activation state by flow cytometry and enzyme-linked immunosorbent assay. Results: Silver-containing titanium dioxide nanocapsules show strong antimicrobial activity against both E. coli and S. aureus and even against a multidrug-resistant strain of S. aureus. We could demonstrate the presence of the nanocapsules in macrophages, but, importantly, the nanocapsules did not affect cell viability and did not activate proinflammatory responses at doses up to 20 µg/mL. Conclusion: Our bactericidal silver-containing titanium dioxide nanocapsules fulfill important prerequisites for biomedical use and represent a promising material for the coating of artificial implants.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Nanocápsulas/química , Animais , Materiais Revestidos Biocompatíveis/química , Escherichia coli/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Nanocápsulas/uso terapêutico , Prata/química , Prata/farmacocinética , Staphylococcus aureus/efeitos dos fármacos , Titânio/química
19.
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
20.
Eur J Histochem ; 64(2)2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32214284

RESUMO

Environmental concerns have driven scientists to research new eco-friendly approaches for the preparation of nanosystems. For this purpose, novel bio-polymers have been selected. Among these, one of the most promising is lignin, which is biodegradable and biocompatible. Additionally, lignin is one of the main by-products of the paper industry and can be re-used in nanosystems building. Lignin-based nanosystems could be used in agriculture, to improve the uptake of bioactive compounds, thus avoiding soil pollution. However, the mechanism of penetration in the plant and the route of transportation within the internal plant tissues are unknown and need to be clearly elucidated. Here we present a method of lignin nanocapsules staining and tracking by fluorochrome: Fluoral Yellow 088, which is a well-suited dye for the tracking of lipids and other oil phases. Two different applications were applied: in the first one fourteen-day plants were soaked with fluorescent nanocapsules (fNCs) pure solution and in the second one, Eragrostis tef plants were laid down on blotting paper and soaked with diluted fNCs solution. Wetting the roots of Teff plantlets with the pure fNCs solution resulted in the most efficient way of nanocapsule entrance. The dyeing of lignin nanocapsules allowed us to track them in Eragrostis tef plant tissues through microscopic observations. In particular, fNCs were proven to be able to permeate roots, reaching xylem vessels where, through water pressure, they reached the leaf.


Assuntos
Eragrostis/metabolismo , Lignina/metabolismo , Nanocápsulas/química , Corantes Fluorescentes/química , Microscopia de Fluorescência/métodos , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Xilema/metabolismo
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