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1.
Nanomedicine ; 52: 102695, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37394106

RESUMO

Chitosan-functionalized magnetite/poly(ε-caprolactone) nanoparticles were formulated by interfacial polymer disposition plus coacervation, and loaded with gemcitabine. That (core/shell)/shell nanostructure was confirmed by electron microscopy, elemental analysis, electrophoretic, and Fourier transform infrared characterizations. A short-term stability study proved the protection against particle aggregation provided by the chitosan shell. Superparamagnetic properties of the nanoparticles were characterized in vitro, while the definition of the longitudinal and transverse relaxivities was an initial indication of their capacity as T2 contrast agents. Safety of the particles was demonstrated in vitro on HFF-1 human fibroblasts, and ex vivo on SCID mice. The nanoparticles demonstrated in vitro pH- and heat-responsive gemcitabine release capabilities. In vivo magnetic resonance imaging studies and Prussian blue visualization of iron deposits in tissue samples defined the improvement in nanoparticle targeting into the tumor when using a magnetic field. This tri-stimuli (magnetite/poly(ε-caprolactone))/chitosan nanostructure could find theranostic applications (biomedical imaging & chemotherapy) against tumors.


Assuntos
Quitosana , Nanopartículas de Magnetita , Nanopartículas , Neoplasias , Camundongos , Animais , Humanos , Óxido Ferroso-Férrico/uso terapêutico , Quitosana/uso terapêutico , Medicina de Precisão , Camundongos SCID , Nanopartículas de Magnetita/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Gencitabina , Imageamento por Ressonância Magnética/métodos
2.
Polymers (Basel) ; 14(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36433039

RESUMO

Magnetite nanorods (MNRs) are synthesized based on the use of hematite nanoparticles of the desired geometry and dimensions as templates. The nanorods are shown to be highly monodisperse, with a 5:1 axial ratio, and with a 275 nm long semiaxis. The MNRs are intended to be employed as magnetic hyperthermia and photothermia agents, and as drug vehicles. To achieve a better control of their photothermia response, the particles are coated with a layer of gold, after applying a branched polyethyleneimine (PEI, 2 kDa molecular weight) shell. Magnetic hyperthermia is performed by application of alternating magnetic fields with frequencies in the range 118-210 kHz and amplitudes up to 22 kA/m. Photothermia is carried out by subjecting the particles to a near-infrared (850 nm) laser, and three monochromatic lasers in the visible spectrum with wavelengths 480 nm, 505 nm, and 638 nm. Best results are obtained with the 505 nm laser, because of the proximity between this wavelength and that of the plasmon resonance. A so-called dual therapy is also tested, and the heating of the samples is found to be faster than with either method separately, so the strengths of the individual fields can be reduced. Due to toxicity concerns with PEI coatings, viability of human hepatoblastoma HepG2 cells was tested after contact with nanorod suspensions up to 500 µg/mL in concentration. It was found that the cell viability was indistinguishable from control systems, so the particles can be considered non-cytotoxic in vitro. Finally, the release of the antitumor drug doxorubicin is investigated for the first time in the presence of the two external fields, and of their combination, with a clear improvement in the rate of drug release in the latter case.

3.
Nanomaterials (Basel) ; 12(3)2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35159698

RESUMO

Therapeutics are habitually characterized by short plasma half-lives and little affinity for targeted cells. To overcome these challenges, nanoparticulate systems have entered into the disease arena. Poly(d,l-lactide-co-glycolide) (PLGA) is one of the most relevant biocompatible materials to construct drug nanocarriers. Understanding the physical chemistry of this copolymer and current knowledge of its biological fate will help in engineering efficient PLGA-based nanomedicines. Surface modification of the nanoparticle structure has been proposed as a required functionalization to optimize the performance in biological systems and to localize the PLGA colloid into the site of action. In this review, a background is provided on the properties and biodegradation of the copolymer. Methods to formulate PLGA nanoparticles, as well as their in vitro performance and in vivo fate, are briefly discussed. In addition, a special focus is placed on the analysis of current research in the use of surface modification strategies to engineer PLGA nanoparticles, i.e., PEGylation and the use of PEG alternatives, surfactants and lipids to improve in vitro and in vivo stability and to create hydrophilic shells or stealth protection for the nanoparticle. Finally, an update on the use of ligands to decorate the surface of PLGA nanomedicines is included in the review.

4.
Front Immunol ; 13: 1077914, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36700196

RESUMO

Introduction: Spondyloarthritis (SpA) is a common autoinflammatory disease. S100A8/ S100A9 alarmin is strongly expressed in the synovial sublining layers of psoriatic arthritis. S100A8/ S100A9 is the most abundant protein in rheumatoid arthritis synovial fluid (SF) and has a key role in promoting IL-6 expression in fibroblast-like synoviocytes (FLS). The molecular mechanisms and the role of S100-alarmins in the synovial microenvironment of SpA have never been demonstrated. Methods and Results: Here, we confirm the effect of the synovial microenvironment of peripheral SpA on interleukin-6 (IL-6) and metalloproteinase (MMP)-9 production by FLS. MMP-9 expression and activity were detected, which were reduced in the presence of anti-IL-6R. Analyzing cell signaling mechanisms, we found that stimulation with IL-6 co-triggered MMP-9 and IL-10 secretion. MMP-9 secretion depended on JNK and p38 MAPKs, whereas IL-10 secretion was dependent on the JAK pathway as a potential feedback mechanism controlling IL-6-induced MMP-9 expression. Using a proteomic approach, we identified S100A8 in the peripheral SpA SF. This presence was confirmed by immunoblotting. S100A8 increased the IL-6 secretion via ERK and p38 MAPK pathways. Furthermore, anti-S100A8/A9 reduced both IL-6 and MMP-9 production induced by SpA SF in FLS. Discussion: Our data reveal a marked relationship between S100A8 alarmin with IL-6 and MMP-9 secretion by FLS in the real synovial microenvironment of peripheral SpA. These results identify a mechanism linking S100A8 to the pathogenesis of peripheral SpA.


Assuntos
Calgranulina A , Interleucina-6 , Espondilartrite , Humanos , Alarminas/metabolismo , Calgranulina A/metabolismo , Calgranulina B/metabolismo , Fibroblastos/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteômica , Espondilartrite/patologia
5.
Pharmaceutics ; 13(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34452193

RESUMO

A (core/shell)/shell nanostructure (production performance ≈ 50%, mean diameter ≈ 330 nm) was built using maghemite, PLGA, and chitosan. An extensive characterization proved the complete inclusion of the maghemite nuclei into the PLGA matrix (by nanoprecipitation solvent evaporation) and the disposition of the chitosan shell onto the nanocomposite (by coacervation). Short-term stability and the adequate magnetism of the nanocomposites were demonstrated by size and electrokinetic determinations, and by defining the first magnetization curve and the responsiveness of the colloid to a permanent magnet, respectively. Safety of the nanoparticles was postulated when considering the results from blood compatibility studies, and toxicity assays against human colonic CCD-18 fibroblasts and colon carcinoma T-84 cells. Cisplatin incorporation to the PLGA matrix generated appropriate loading values (≈15%), and a dual pH- and heat (hyperthermia)-responsive drug release behaviour (≈4.7-fold faster release at pH 5.0 and 45 °C compared to pH 7.4 and 37 °C). The half maximal inhibitory concentration of the cisplatin-loaded nanoparticles against human lung adenocarcinoma A-549 cells was ≈1.6-fold less than that of the free chemotherapeutic. Such a biocompatible and tri-stimuli responsive (maghemite/PLGA)/chitosan nanostructure may found a promising use for the effective treatment of lung cancer.

6.
J Mater Chem B ; 9(24): 4963-4980, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34114575

RESUMO

(Maghemite/poly(d,l-lactide-co-glycolide))/chitosan (core/shell)/shell nanoparticles have been prepared reproducibly by nanoprecipitation solvent evaporation plus coacervation (production performance ≈ 45%, average size ≈ 325 nm). Transmission electron microscopy, energy dispersive X-ray spectroscopy, electrophoretic determinations, and X-ray diffraction patterns demonstrated the satisfactory embedment of iron oxide nanocores within the solid polymer matrix and the formation of an external shell of chitosan in the nanostructure. The adequate magnetic responsiveness of the nanocomposites was characterized in vitro by hysteresis cycle determinations and by visualization of the nanosystem under the influence of a 0.4 T permanent magnet. Safety and biocompatibility of the (core/shell)/shell particles were based on in vitro haemocompatibility studies and cytotoxicity tests against HFF-1 human foreskin fibroblasts and on ex vivo toxicity assessments on tissue samples from Balb/c mice. Transversal relaxivities, determined in vitro at a low magnetic field of 1.44 T, demonstrated their capability as T2 contrast agents for magnetic resonance imaging, being comparable to that of some iron oxide-based contrast agents. Heating properties were evaluated in a high frequency alternating electromagnetic gradient: a constant maximum temperature of ≈46 °C was generated within ≈50 min, while antitumour hyperthermia tests on T-84 colonic adenocarcinoma cells proved the relevant decrease in cell viability (to ≈ 39%) when treated with the nanosystem under the influence of that electromagnetic field. Finally, in vivo magnetic resonance imaging studies and ex vivo histology determinations of iron deposits postulated the efficacy of chitosan to provide long-circulating capabilities to the nanocomposites, retarding nanoparticle recognition by the mononuclear phagocyte system. To our knowledge, this is the first study describing such a type of biocompatible and long-circulating nanoplatform with promising theranostic applications (biomedical imaging and hyperthermia) against cancer.


Assuntos
Quitosana/química , Engenharia , Hipertermia Induzida , Nanopartículas de Magnetita/química , Nanocompostos/química , Neoplasias/tratamento farmacológico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Nanocompostos/uso terapêutico
7.
Polymers (Basel) ; 12(12)2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33255803

RESUMO

A reproducible and efficient interfacial polymer disposition method has been used to formulate magnetite/poly(ε-caprolactone) (core/shell) nanoparticles (average size ≈ 125 nm, production performance ≈ 90%). To demonstrate that the iron oxide nuclei were satisfactorily embedded within the polymeric solid matrix, a complete analysis of these nanocomposites by, e.g., electron microscopy visualizations, energy dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, electrophoresis, and contact angle goniometry was conducted. The magnetic responsive behaviour of these nanoparticles was quantitatively characterized by the hysteresis cycle and qualitatively investigated by visualization of the colloid under exposure to a 0.4 T magnet. Gemcitabine entrapment into the polymeric shell reported adequate drug loading values (≈11%), and a biphasic and pH-responsive drug release profile (≈ four-fold faster Gemcitabine release at pH 5.0 compared to pH 7.4). Cytotoxicity studies in MCF-7 human breast cancer cells proved that the half maximal inhibitory concentration of Gem-loaded nanocomposites was ≈ two-fold less than that of the free drug. Therefore, these core/shell nanoparticles could have great possibilities as a magnetically targeted Gemcitabine delivery system for breast cancer treatment.

8.
Pharm Dev Technol ; 25(7): 892-898, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32321344

RESUMO

Praziquantel (PZQ), a broad spectrum anthelmintic drug, cannot be found in acceptable dosage forms for elderly patients, paediatric patients, and for veterinary use. In fact, very little has been done up to now in the formulation of liquid dosage forms, being they always formulated for parenteral administration. To beat this important challenge, it was accomplished a comprehensive analysis of the influence of two elementary physicochemical aspects, i.e. surface thermodynamic and electrokinetic properties, on the colloidal stability of PZQ nanosuspensions. The hydrophobic character of the drug, intensely determining the flocculation curves, was confirmed by the thermodynamic characterization. The electrophoretic characterization, in combination with the sedimentation and relative absorbance versus time curves, highlighted that the electrical double layer thickness and the surface charge can play an essential role in the stability of the pharmaceutical colloid. Finally, it was demonstrated that controlling the pH values and the incorporation of electrolytes can help in formulating PZQ aqueous nanosuspensions with appropriate stability and redispersibility behaviours for pharmaceutical use.


Assuntos
Anti-Helmínticos/síntese química , Composição de Medicamentos/métodos , Nanosferas/química , Praziquantel/síntese química , Anti-Helmínticos/farmacocinética , Química Farmacêutica/métodos , Eletrólitos/síntese química , Eletrólitos/farmacocinética , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Nanosferas/metabolismo , Praziquantel/farmacocinética , Água/química , Água/metabolismo
9.
Expert Opin Ther Pat ; 29(11): 891-907, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31603360

RESUMO

Introduction: Pharmacotherapy is limited by the inefficient drug targeting of non-healthy cells/tissues. In this pharmacological landscape, liposomes are contributing to the impulse given by Nanotechnology to optimize drug therapy. Areas covered: The analysis of the state-of-the-art in liposomal formulations for drug delivery purposes have underlined that lately published patents (since 2014) are exploring alternative compositions and ways to optimize the stability and drug loading content/release profile. These improvements are complemented by improved long-circulating structures and further liposome functionalizations, which have definitively opened the road for the (co-)delivery of therapeutics to the site of action. Liposomes are also contributing to new drug delivery approaches involving the generation of extracellular vesicles by targeted cells, while opening new ways to combine disease diagnosis and therapy (theranosis). Expert opinion: Patent publications on liposomal formulations have expanded new ways in drug delivery. New lipid compositions and strategies to optimize stability and drug vehiculization capabilities have settle solid pillars in liposome fabrication. Despite, their architecture has been satisfactorily adapted for combining passive and active drug targeting concepts, new inputs of liposomes into the disease arena should answer for: a simple/scalable/cost-effective formulation; a safe/stable/controllable formulation meeting quality control regulations; and, a confirmed therapeutic efficiency in clinical investigations.


Assuntos
Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos , Lipídeos/química , Animais , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Lipossomos , Nanotecnologia/métodos , Patentes como Assunto
10.
Neuroimmunomodulation ; 25(3): 153-162, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30304732

RESUMO

OBJECTIVE: Circadian rhythms are generated by the suprachiasmatic nucleus of the hypothalamus and involve rhythmic expression of clock genes and proteins. This rhythmicity is transferred to peripheral tissues by neural and hormonal signals. Late pregnancy is considered a state of inflammation which impacts on peripheral tissues such as joints. Tumor necrosis factor (TNF) mediates inflammatory and circadian responses through its p55 receptor (TNFRp55). Neuroimmunoendocrine interactions in joints have not been studied completely. The purpose of this study was to analyze these interactions, investigating the circadian rhythms of progesterone (Pg) and pro- and anti-inflammatory cytokines in the joints at the end of pregnancy (gestational day 18). Moreover, the impact of TNFRp55 deficiency on these temporal oscillations was explored. METHODS: Wild-type and TNFRp55-deficient (KO) C57BL/6 mice were kept under constant darkness in order to study their endogenous circadian rhythms. The expression of the clock genes Bmal1 and Per1 at circadian time 7 was studied by reverse transcription polymerase chain reaction in the ankle joints of nonpregnant and pregnant (gestational day 18) mice. In late pregnancy, Pg and the cytokines interleukin 17 (IL-17), IL-6, and IL-10 were measured in the joints throughout a 24-h period by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. RESULTS: A significant increase in Bmal1 and Per1 mRNA expression was detected in the joints of pregnant KO mice. Furthermore, KO mice displayed a desynchronization of articular Pg and cytokine production. CONCLUSIONS: Our results show that TNF, via TNFRp55 signaling, modulates articular Pg and cytokine circadian rhythms in late pregnancy. These findings suggest a temporal neuroimmunoendocrine association in peripheral tissues in late pregnancy.


Assuntos
Ritmo Circadiano/fisiologia , Citocinas/metabolismo , Articulações/metabolismo , Neuroimunomodulação/fisiologia , Progesterona/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Receptores Chamariz do Fator de Necrose Tumoral/metabolismo , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Gravidez
11.
Colloids Surf B Biointerfaces ; 171: 553-565, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30096477

RESUMO

Magnetoliposomes (MLPs) offer many new possibilities in cancer therapy and diagnosis, including the transport of antitumor drugs, hyperthermia treatment, detection using imaging techniques, and even cell migration. However, high biocompatibility and functionality after cell internalization are essential to their successful application. We synthesized maghemite nanoparticles (γ-Fe2O3) by oxidizing magnetite cores (Fe3O4) and coating them with phosphatidylcholine (PC) liposomes, obtained using the thin film hydration method, to generate MLPs. The MLPs were tested in vitro, using human tumor and non-tumor colon cell lines, for cytotoxicity, cell uptake and cellular distribution, and magnetically-induced cell mobility. In addition, blood cells biocompatibility studies were performed. The mean size of the MLPs, with a core of γ-Fe2O3 completely surrounded by PC liposomes, was 90 ± 20 nm, showing a soft magnetic character and a great biocompatibility in all the cell lines assayed including blood cells. Prussian blue staining showed a high MLP cell uptake with maximum internalization at 24 h. TEM analysis showed the MLPs surrounded by the cell membrane and in the cell periphery, suggesting internalization by endocytosis and/or macropinocytosis. Interestingly, the mitochondria presented MLP accumulations, particularly in tumor cells. Finally, MLPs within colon cancer cells were able to induce cell migration when a magnetic field was applied in vitro, indicating the functionality of our nanoformulation. A promising biomedical application of these MLPs is anticipated based on their physical, chemical and biological properties.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Compostos Férricos/química , Nanopartículas de Magnetita/química , Nanotecnologia , Fosfatidilcolinas/química , Animais , Antineoplásicos/química , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Neoplasias Colorretais/patologia , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Férricos/síntese química , Compostos Férricos/farmacologia , Humanos , Lipossomos/química , Camundongos , Tamanho da Partícula , Fosfatidilcolinas/farmacologia , Células RAW 264.7 , Propriedades de Superfície
12.
Rev. Fac. Med. UNAM ; 61(4): 38-40, jul.-ago. 2018. graf
Artigo em Espanhol | LILACS | ID: biblio-977001

RESUMO

Resumen La apendagitis aguda es una causa de dolor abdominal subdiagnosticada, ya que puede simular un cuadro de diverticulitis o apendicitis. Se debe a una torsión o trombosis del pedículo vascular de un apéndice epiploico que resulta en isquemia e infarto. El diagnóstico suele ser un hallazgo radiológico; sin embargo, tiene un curso autolimitado con resolución espontánea de 5 a 7 días.


Abstract Acute appendagitis is a cause of undiagnosed abdominal pain, as it may mimic diverticulitis or appendicitis. Torsion or thrombosis of the vascular pedicle of an epiploic appendage resulting in ischemia and infarction is due. The diagnosis is usually a radiological finding; however it has a self-limited course with spontaneous resolution of 5 to 7 days.

13.
Rev. Fac. Med. UNAM ; 61(2): 20-23, mar.-abr. 2018. graf
Artigo em Espanhol | LILACS | ID: biblio-957158

RESUMO

Resumen Las malformaciones congénitas müllerianas son una entidad clínica de relevancia, más significativa en pacientes que se encuentran en edad reproductiva. Existen múltiples avances tecnológicos que contribuyen al diagnóstico por imagen de las malformaciones, que van desde simples hasta complejas, con el objetivo de ofrecer el mejor tratamiento.


Abstract Müllerian congenital malformations are a relevant clinical entity, most significantly in patients of reproductive age. There are multiple technological advances that contribute in the diagnosis by image of the malformations that go from simple to complex; with the aim of offering the best treatment.

14.
J Pharm Pharmacol ; 70(4): 488-497, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29380384

RESUMO

OBJECTIVES: Liposomes have attracted the attention of researchers due to their potential to act as drug delivery systems for cancer treatment. The present investigation aimed to develop liposomes loaded with prednisolone base and the evaluation of the antiproliferative effect on human colon carcinoma cell lines. METHODS: Liposomes were elaborated by following a reproducible thin film hydration technique. The physicochemical characterization of liposomes included photon correlation spectroscopy, microscopy analysis, Fourier transform infrared spectroscopy, rheological behaviour and electrophoresis. On the basis of these data and drug loading values, the best formulation was selected. Stability and drug release properties were also tested. KEY FINDINGS: Resulting liposomes exhibited optimal physicochemical and stability properties, an excellent haemocompatibility and direct antiproliferative effect on human colon carcinoma T-84 cell lines. CONCLUSIONS: This study shows direct antitumour effect of prednisolone liposomal formulation, which opens the door for liposomal glucocorticoids as novel antitumour agents.


Assuntos
Antineoplásicos Hormonais/toxicidade , Neoplasias do Colo , Citotoxinas/toxicidade , Nanotecnologia/métodos , Prednisolona/toxicidade , Antineoplásicos Hormonais/química , Antineoplásicos Hormonais/farmacocinética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Citotoxinas/química , Citotoxinas/farmacocinética , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Liberação Controlada de Fármacos/fisiologia , Humanos , Lipossomos , Prednisolona/química , Prednisolona/farmacocinética
15.
Int J Pharm ; 530(1-2): 155-164, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28739502

RESUMO

In the present investigation solvent displacement or nanoprecipitation, and emulsion/solvent evaporation methods were utilized to optimize poly(D,L-lactide-co-glycolide) nanoparticles for the vehiculization of the 5-fluorouracil. Formulation components from both the aqueous and organic phases, as well as, operating conditions were varied. Particles were characterized in terms of particle size and morphology, electrical properties, rheology, drug loading, stability, and drug release. Furthermore, in vitro cytotoxicity on human colon cells and different colon carcinoma cells was evaluated. Four types of nanoparticles were selected for drug loading, revealing differences between variables. Low viscosity values and their Newtonian behavior could assure the suitability of the nanoformulation for the intravenous route of administration. The greatest drug entrapment efficiency and best stability was achieved when the chemotherapeutic agent was incorporated into the internal aqueous phase of particles prepared by double emulsion/solvent evaporation. However, a more sustained drug release at pH 7.4 was possible when 5-fluorouracil was added to the external aqueous phase. These were the nanoformulations reporting the greatest antiproliferative efficacy compared with the free drug. The nanocarrier can optimize the antitumor activity of 5-fluorouracil, thus being a potential nanotool against colon cancer.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Portadores de Fármacos/química , Fluoruracila/química , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Linhagem Celular Tumoral , Humanos , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
16.
AAPS PharmSciTech ; 18(8): 3042-3052, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28508129

RESUMO

A great attention is presently paid to the design of drug delivery vehicles based on surface-modified magnetic nanoparticles. They can, in principle, be directed to a desired target area for releasing their drug payload, a process triggered by pH, temperature, radiation, or even magnetic field. To this, the possibility of forming part of diagnostic tools by enhanced magnetic resonance imaging or that of further treatment by magnetic hyperthermia can be added. Bare particles are rapidly eliminated from the bloodstream by the phagocyte mononuclear system, leading to short biological half-life. It is hence required to coat them in order to increase their biocompatibility and facilitate the drug incorporation. In this work, magnetite nanoparticles were coated with poly(butylcyanoacrylate) (PBCA) manufactured and characterized with regard to their physical properties and their suitability as a platform for magnetically controlled drug delivery. The average diameter of magnetite and core-shell nanoparticles was 97 ± 19 and 140 ± 20 nm, respectively. Infrared analysis, electrophoretic mobility, surface thermodynamics analysis, and X-ray diffraction all confirmed that the magnetic particles were sufficiently covered by the polymer in the composite nanoparticles. In addition, assays using normal (CCD-18 and MCF-10A) and tumoral (T-84 and MCF-7) cell lines derived from colon and breast tissue, respectively, demonstrated that nanocomposites have low or negligible cytotoxicity. It is concluded that PBCA-coated magnetite core-shell nanoparticles represent a remarkable promise as a platform for magnetically controlled drug delivery.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Embucrilato/administração & dosagem , Nanopartículas de Magnetita/administração & dosagem , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Embucrilato/química , Células Hep G2 , Humanos , Células MCF-7 , Nanopartículas de Magnetita/química , Difração de Raios X
17.
Eur J Pharm Sci ; 102: 24-34, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28219748

RESUMO

Poly(ε-caprolactone) (PCL) nanoparticles (NPs) offer many possibilities for drug transport because of their good physicochemical properties and biocompatibility. Doxorubicin-loaded PCL NPs have been synthesized to try to reduce the toxicity of doxorubicin (DOX) for healthy tissues and enhance its antitumor effect in two tumor models, breast and lung cancer, which have a high incidence in the global population. PCL NPs were synthesized using a modified nanoprecipitation solvent evaporation method. The in vitro toxicity of PCL NPs was evaluated in breast and lung cancer cell lines from both humans and mice, as was the inhibition of cell proliferation and cell uptake of DOX-loaded PCL NPs compared to free DOX. Breast and lung cancer xenografts were used to study the in vivo antitumor effect of DOX-loaded NPs. Moreover, healthy mice were used for in vivo toxicity studies including weight loss, blood toxicity and tissue damage. The results showed good biocompatibility of PCL NPs in vitro, as well as a significant increase in the cytotoxicity and cell uptake of the drug-loaded in PCL NPs, which induced almost a 98% decrease of the IC50 (E0771 breast cancer cells). Likewise, DOX-loaded PCL NPs led to a greater reduction in tumor volume (≈36%) in studies with C57BL/6 mice compared to free DOX in both lung and breast tumor xenograft models. Nevertheless, no differences were found in terms of mouse weight. Only in the lung cancer model were significant differences in mice survival observed. In addition, DOX-loaded PCL NPs were able to reduce myocardial and blood toxicity in mice compared to free DOX. Our results showed that DOX-loaded PCL NPs were biocompatible, enhanced the antitumor effect of DOX and reduced its toxicity, suggesting that they may have an important potential application in lung and breast cancer treatments.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Mamárias Experimentais/tratamento farmacológico , Nanopartículas/administração & dosagem , Poliésteres/administração & dosagem , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/uso terapêutico , Poliésteres/química , Poliésteres/farmacologia , Poliésteres/uso terapêutico , Ratos
18.
Int J Pharm ; 516(1-2): 61-70, 2017 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-27825867

RESUMO

5-Fluorouracil (5-FU) is a broad spectrum cytotoxic agent being used in chemotherapy of malignancies. However, 5-FU shows a number of limitations like short half-life, non-selective biodistribution, and the development of drug resistances by tumour cells. It was investigated the potential use of folic acid-decorated and PEGylated poly(D,L-lactide-co-glycolide) nanoparticles (FOL-PEG-PLGA NPs) for the targeted delivery of 5-FU to colon and breast cancers. PEG-PLGA and FOL-PEG-PLGA conjugates were synthesized and characterized. NPs of PLGA, PEG-PLGA, and FOL-PEG-PLGA were prepared by nanoprecipitation under optimal formulation conditions. They were found to be haemocompatible, and exhibited negligible cytotoxicity in normal (CCD-18 and MCF-10A) and tumour (HT-29 and MCF-7) human cell lines. 5-FU loading capabilities were also defined, and the NPs exhibited an initial burst drug release followed by a sustained 5-FU release. In vitro cytotoxicity studies in folate-overexpressed HT-29 colon cancer cells and MCF-7 breast cancer cells demonstrated that the half maximal inhibitory concentration (IC50) of 5-FU-loaded FOL-PEG-PLGA NPs was approximately 4-fold less than that of the 5-FU-loaded PLGA NPs (p<0.05). Consequently, FOL-PEG-PLGA NPs could have great potential as a targeted 5-FU delivery system for colon and breast cancer treatment.


Assuntos
Sistemas de Liberação de Medicamentos , Fluoruracila/administração & dosagem , Ácido Fólico/administração & dosagem , Nanopartículas , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular , Química Farmacêutica/métodos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Portadores de Fármacos/química , Feminino , Fluoruracila/farmacologia , Ácido Fólico/farmacologia , Células HT29 , Humanos , Concentração Inibidora 50 , Células MCF-7 , Poliésteres/química , Polietilenoglicóis/química , Distribuição Tecidual
19.
Int J Pharm ; 518(1-2): 270-280, 2017 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-28011343

RESUMO

It is described the reproducible formulation and complete physicochemical characterization of nanohybrids based on magnetite (Fe3O4) cores embedded within a polyethylenimine (PEI) matrix. Particle size, surface electrical charge, X-ray diffraction and Fourier transform infrared spectroscopy (FTIR) analyses, and magnetic field-responsive behaviour characterizations defined that the 4:3 (Fe3O4:PEI) weight proportion led to the best production performances of magnetically responsive nanocomposites in which the magnetic nuclei are completely covered by the polymeric shell. Agarose gel electrophoresis assays demonstrated the capacity of the Fe3O4/PEI particles to condense, release, and protect the DNA against enzymatic degradation. In vitro assays were performed to evaluate the transfection efficiency (up to 4.5% of transfected HEK-293 cells at a 10/1 PEI/DNA ratio), iron absorption by D1-mesenchymal stem cells (D1-MSCs, high values after only 15min of magnetic incubation), influence on metabolic activity (negligible effect up to 44µg nanocomposites/105 cells), and cell isolation capacity of the core/shell particles (significant increase in the retention of D1-MSCs transduced with green fluorescent protein). The Fe3O4/PEI nanohybrids hold promising characteristics suggestive of their capacity for transfection and cell isolation applications.


Assuntos
DNA/química , Óxido Ferroso-Férrico/química , Nanopartículas/química , Polietilenoimina/química , Animais , Sobrevivência Celular , Células Cultivadas , DNA/administração & dosagem , Óxido Ferroso-Férrico/administração & dosagem , Proteínas de Fluorescência Verde/genética , Células HEK293 , Humanos , Células-Tronco Mesenquimais , Camundongos , Nanopartículas/administração & dosagem , Tamanho da Partícula , Polietilenoimina/administração & dosagem , Espectroscopia de Infravermelho com Transformada de Fourier , Transfecção , Difração de Raios X
20.
Rev. Fac. Med. UNAM ; 59(6): 23-26, nov.-dic. 2016. graf
Artigo em Espanhol | LILACS | ID: biblio-957112

RESUMO

Resumen La obesidad es considerada en la actualidad como una epidemia mundial en niños, adolescentes y adultos. La causa fundamental del sobrepeso y la obesidad es un desequilibrio energético entre las calorías consumidas y las gastadas. Se considera además como una enfermedad que conlleva al desarrollo de otras enfermedades crónico-degenerativas como la diabetes, la hipertensión y las enfermedades cardiovasculares principalmente. De ahí que es imprescindible incrementar los recursos de salud, reforzar la información educativa y utilizar los recursos médico-quirúrgicos disponibles que han demostrado excelentes resultados para lograr la reducción de los índices de obesidad en nuestro país y así evitar el desarrollo de comorbilidades.


Abstract Obesity is considered today as an epidemic world in children, adolescents and adults. The principal cause of overweight and obesity in an energy imbalance between consumed calories and expended. It is also considered as a disease that leads to the development of other cronic diseases such as diabetes, hypertension and cardiovascular diseases mainly. Of hence is important to increase health resources, strengthen the educational information and utilize medical-surgical available today that have shown excellent results in obesity reduction rates in our country population and prevent co-morbidities development.

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