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1.
Int Orthod ; 22(2): 100871, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38613861

RESUMO

OBJECTIVES: This study aimed to prepare a glass ionomer (GI) cement reinforced with silver-hydroxyapatite-silica (Ag/HA/Si) hybrid nanoparticles and assess its compressive strength and fluoride release profile. MATERIAL AND METHODS: In this in vitro, experimental study, 60 cylindrical specimens were fabricated with 4mm diameter and 6mm height in 6 groups (n=10) using BracePaste composite, GC Fuji II LC pure RMGI, and RMGI reinforced with 0.1wt%, 0.5wt%, 1wt%, and 2wt% Ag/HA/Si hybrid nanoparticles. The specimens were subjected to compressive force in a universal testing machine to measure their compressive strength (MPa). To assess their fluoride release profile, discs with 3mm diameter and 2mm thickness were fabricated from Fuji II LC pure resin-modified glass ionomer (RMGI), and RMGI with 0.1wt%, 0.5wt%, 1wt%, and 2wt% hybrid nanoparticles, and the concentration of released fluoride was measured by a digital ion-selective electrode. Data were analysed by ANOVA and Scheffe test (alpha=0.05). RESULTS: The compressive strength was 114.14MPa for BracePaste composite, and 97.14, 97.84, 100.65, 109.5, and 89.33MPa for GI groups with 0%, 0.1%, 0.5%, 1% and 2% hybrid nanoparticles, respectively, with no significant difference among them (P=0.665). Addition of 1% (0.21±0.07µg/mL, P=0.029) and 2% (0.45±0.22µg/mL, P=0.000) hybrid nanoparticles to RMGI significantly increased the amount of released fluoride, compared with the control group (0.09±0.03µg/mL). CONCLUSIONS: Addition of Ag/HA/Si hybrid nanoparticles to RMGI in the tested concentrations had no significant effect on its compressive strength but addition of 1wt% and 2wt% concentrations of Ag/HA/Si hybrid nanoparticles increased its fluoride release potential.


Assuntos
Força Compressiva , Durapatita , Fluoretos , Cimentos de Ionômeros de Vidro , Teste de Materiais , Nanopartículas , Dióxido de Silício , Prata , Cimentos de Ionômeros de Vidro/química , Fluoretos/química , Prata/química , Dióxido de Silício/química , Nanopartículas/química , Durapatita/química , Técnicas In Vitro , Análise do Estresse Dentário , Humanos
2.
Int J Pharm ; 645: 123418, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37716484

RESUMO

Multifunctional nanocarriers are increasingly promising for disease treatment aimed at finding effective therapy and overcoming barriers in drug delivery. Herein, valine conjugated chitosan (VLCS) was used for surface modification of nanocarriers (NCs) based on Poly (ε-caprolactone)-Poly (ethylene glycol)-Poly (ε-caprolactone) (PCL-PEG-PCL) triblock copolymers (NCs@VLCS). The nanocarriers were co-loaded with rivastigmine (RV) and quercetin (QT) to yield the final RV/QT-NCs@VLCS as a multifunctional nanocarrier for Alzheimer's disease (AD) treatment. The large amino acid transporter 1 (LAT-1) was selected for the direction of the NCs to the brain. The biocompatibility of the nanocarrier was studied in HEK-293 and SH-SY5Y cells and rats. The Morris water maze test demonstrated a faster regain of memory loss with RV/QT-NCs@VLCS compared to the other groups. Furthermore, RV/QT-NCs@VLCS and RV/QT-NCs improved GSH depletion induced by scopolamine (SCO), with RV/QT-NCs@VLCS having a superior effect. The real-time PCR analysis revealed that co-delivery of RV and QT by NCs@VLCS showed significantly higher efficacy than sole delivery of RV. RV/QT-NCs@VLCS treatment also modulated the expression of BDNF, ACHE, and TNF-α. The findings revealed that NCs@VLCS co-loaded with RV and QT, significantly increased efficacy relative to the single use of RV and could be considered a potent multifunctional drug delivery system for Alzheimer's treatment.


Assuntos
Doença de Alzheimer , Neuroblastoma , Humanos , Ratos , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Rivastigmina/uso terapêutico , Quercetina/uso terapêutico , Células HEK293 , Neuroblastoma/tratamento farmacológico , Polímeros/uso terapêutico , Polietilenoglicóis/química , Poliésteres/química , Portadores de Fármacos/química
3.
Int Orthod ; 21(3): 100761, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37244178

RESUMO

OBJECTIVES: This study aimed to assess the effect of addition of silica-hydroxyapatite-silver (Si-HA-Ag) hybrid nanoparticles to light-cure glass ionomer (GI) on shear bond strength (SBS) of metal brackets bonded with this adhesive and the adhesive remnant index (ARI) score. MATERIAL AND METHODS: In this in vitro experimental study, 50 sound extracted premolars were assigned to 5 groups (n=10) for orthodontic metal bracket bonding with BracePaste® composite, Fuji ORTHO™ pure resin modified GI (RMGI), and RMGI reinforced with 2wt%, 5wt% and 10wt% Si-HA-Ag nanoparticles. The SBS of brackets was measured by a universal testing machine. Debonded specimens were inspected under a stereomicroscope at×10 magnification to determine the ARI score. Data were analyzed by one-way ANOVA, Scheffe test, Chi-square test, and Fisher's exact test (alpha=0.05). RESULTS: The maximum mean SBS was recorded in BracePaste® composite followed by 2% RMGI, 0% RMGI, 5% RMGI and 10% RMGI. Only the difference between the BracePaste® composite and 10% RMGI was significant in this regard (P=0.006). The groups were not significantly different regarding the ARI scores (P=0.665). All the SBS values were within the clinically acceptable range. CONCLUSION: Addition of 2wt% and 5wt% Si-HA-Ag hybrid nanoparticles to RMGI as orthodontic adhesive caused no significant change in SBS of orthodontic metal brackets while addition of 10wt% hybrid nanoparticles significantly decreased the SBS. Nonetheless, all the SBS values were within the clinically acceptable range. Addition of hybrid nanoparticles had no significant effect on the ARI score.


Assuntos
Colagem Dentária , Nanopartículas Metálicas , Braquetes Ortodônticos , Humanos , Cimentos Dentários , Prata , Cimentos de Resina/química , Dióxido de Silício , Hidroxiapatitas , Resistência ao Cisalhamento , Teste de Materiais , Propriedades de Superfície , Análise do Estresse Dentário
4.
Int J Pharm ; 628: 122260, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36241033

RESUMO

The application of nano-based materials in intelligent, innovative drug delivery systems (SDDS) is developing rapidly to treat infectious diseases like malaria. In the present study, magnetite (Fe3O4) nanocomposite coated with heparin (Hep) was designed to deliver quinine (Q) for anti-plasmodial purposes. The MTT assay, Artemia salina lethality, and hemolysis test were adopted to evaluate the nanocomposite's cytotoxicity, biotoxicity, and biocompatibility. The cumulative drug release profile revealed that this Q-loaded nanocomposite could accelerate the release of its payload in an acidic condition (pH 5.4), which mimics the digestive vacuole (DV) of the parasite. The in vivo anti-plasmodial activity indicated that the Q-loaded nanocomposite exhibited great anti-plasmodial activity than free quinine. The experimental results showed that the presence of heparin on the surface of the nanocomposite could significantly reduce cytotoxicity, biotoxicity, and acute toxicity. Besides, SEM, TEM, and HRTEM images indicated that nonstabilized Fe3O4 particles have significant aggregation, but the presence of heparin can play a role as a stabilizing agent. These biocompatible, nontoxic nanocomposites offer great potential for anti-plasmodial drug delivery.


Assuntos
Heparina , Nanocompostos , Quinina/farmacologia , Liberação Controlada de Fármacos , Fenômenos Magnéticos
5.
J Biomater Sci Polym Ed ; 33(3): 279-298, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34547988

RESUMO

Multifunctional nanocarriers as a promising platform could provide numerous opportunities in the field of drug delivery. Drug carriers loaded with both magnetic nanoparticles (MNPs) and therapeutic agents would allow the combination of chemotherapy with the possibility of monitoring or controlling the distribution of the nano vehicles in the body which may improve the effectiveness of the therapy. Furthermore, by applying these strategies, triggering drug release and/or synergistic hyperthermia treatment are also reachable. This study aimed to explore the potential of the quercetin (QUR) loaded magnetic nano-micelles for improving drug bioavailability while reducing the drug adverse effects. The bio-safety of developed QUR loaded magnetic nano-micelles (QMNMs) were conducted via mitochondrial toxicity using isolated rat liver mitochondria including glutathione (GSH), malondialdehyde (MDA), and the ferric reducing ability of plasma (FRAP). QMNMs with a mean particle size of 85 nm (PDI value of 0.269) and great physical stability were produced. Also, TEM images indicated that the prepared QMNMs were semi-spherical in shape. These findings also showed that the constructed QMNMs, as a pH-sensitive drug delivery system, exhibited a stable and high rate of QUR release under mildly acidic conditions pH (5.3) compared to neutral pH (7.4). The most striking result to emerge from the data is that an investigation of various mitochondrial functional parameters revealed that both QMNMs and QUR have no specific mitochondrial toxicity. Altogether, these results offer overwhelming evidence for the bio-safety of QMNMs and might be used as an effective drug delivery system for targeting and stimuli-responsive QUR delivery.


Assuntos
Micelas , Quercetina , Animais , Doxorrubicina , Portadores de Fármacos/toxicidade , Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio , Fenômenos Magnéticos , Mitocôndrias Hepáticas , Tamanho da Partícula , Polímeros , Quercetina/toxicidade , Ratos
6.
Heliyon ; 8(12): e12545, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36619431

RESUMO

This study aimed to directly detect the V617F point mutation of the Janus kinase 2 (JAK2) gene in the target DNA using a FRET-based biosensor. The water-soluble GSH-CdTe-QDs were synthesized by a one-step process, then GSH-QD conjugated to the termini amino-modified oligonucleotides target via carboxylic groups on the QD surface. The prepared QDs-DNA biosensor was applied in the quantitative and rapid detection of V617F mutation with a detection limit of 3 × 10-9 mol L-1 based on the FRET mechanism. In other words, detecting the V617F mutation by bio-sensing technology would be much simpler, cheaper, time-saving, highly sensitive, and more convenient than molecular diagnostic tools. Furthermore, the nano-biosensor was applied to detect the V617F mutation in clinical samples compared to the common ARMS-PCR (Amplification Refractory Mutation System-Polymerase Chain Reaction) standard method. The results revealed that the GSH-capped biosensors would be effective for V617F mutation detection in samples distinguished with satisfactory analytical outcomes. Therefore, the designed fluorescence nanoprobe is suitable for the specific detection of V617F mutation of the JAK2 gene in clinical samples.

7.
J Biomater Appl ; 36(6): 1055-1063, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34304637

RESUMO

In this research, magnetic nanostructured lipid carriers (Mag-NLCs) were synthesized for curcumin (CUR) delivery. NLCs are drug-delivery systems prepared by mixing solid and liquid (oil) lipids. For preparation of NLCs, cetylpalmitate was selected as solid lipid and fish oil as liquid lipid. CUR-Mag-NLCs were prepared using high-pressure homogenization technique and were characterized by methods including X-ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), and dynamic light scattering (DLS). The CUR-Mag-NLCs were developed as a particle with a size of 140 ± 3.6 nm, a polydispersity index of 0.196, and a zeta potential of -22.6 mV. VSM analysis showed that the CUR-Mag-NLCs have excellent magnetic properties. Release rate of the drug was higher at 42 °C than 37 °C, indicating that release of the synthesized nanoparticles is temperature-dependent. Evaluation of mitochondrial toxicity was done using the isolated rats liver mitochondria including glutathione (GSH), malondialdehyde (MDA), and the ferric- reducing ability of plasma (FRAP) assays to study biosafety of the CUR-Mag-NLCs. Results of In vitro study on the isolated mitochondria revealed that both CUR-Mag-NLCs and curcumin have no specific mitochondrial toxicity.


Assuntos
Curcumina , Nanopartículas , Nanoestruturas , Animais , Curcumina/toxicidade , Portadores de Fármacos/toxicidade , Lipídeos/toxicidade , Fenômenos Magnéticos , Mitocôndrias Hepáticas , Nanopartículas/toxicidade , Tamanho da Partícula , Ratos
8.
ACS Biomater Sci Eng ; 7(6): 2701-2715, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34061500

RESUMO

The present study introduces a superparamagnetic nanocomposite, Fe-Si-In, as a T2 magnetic resonance imaging (MRI) contrast agent with a core of iron oxide nanoparticles and a nonporous silica inner shell/carboxymethyl inulin outer shell. Due to its core/shell properties, the structure characterization, biocompatibility, and performance in MRI, as well as its potential as a drug delivery system, were thoroughly evaluated. The results have shown that the synthesized nanocomposite possesses excellent biocompatibility and acceptable magnetization (Ms = 20 emu g-1). It also has the potential to be a nanocarrier for drug delivery purposes, as evidenced by the results of curcumin administration studies. The developed nanocomposite has shown excellent performance in MRI, while the in vitro relaxivity measurements reveal a stronger T2 relaxivity (r2 = 223.2 ms) compared to the commercial samples available in the market. Furthermore, the in vivo MRI studies demonstrate an excellent contrast between injured livers and normal ones in rats which again upholds the high performance of Fe-Si-In in MRI diagnostics.


Assuntos
Inulina , Falência Hepática Aguda , Animais , Nanopartículas Magnéticas de Óxido de Ferro , Imageamento por Ressonância Magnética , Medicina de Precisão , Ratos
9.
J Biomater Sci Polym Ed ; 32(10): 1356-1369, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33882784

RESUMO

This paper proposed an engineered mesoporous silica-coated Fe3O4 nanoparticle, PVPMSFe, prepared by a sol-gel/surface-protected etching mechanism as an MRI T2 contrast agent. To this end, the structural characterization of the nanocomposite was performed by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) method, VSM, thermogravimetric analysis (TGA), TEM, FESEM, and energy-dispersive X-ray scanning electron microscopy (EDS). The findings show that the synthesized nanocomposite has a mesoporous structure with an average particle size of 11.8 nm and excellent magnetization properties. The biocompatibility of PVPMSFe was investigated by MTT assay and hemolysis assay of red blood cells and the results indicate that PVPMSFe has favorable biocompatibility. Besides, the effect of PVPMSFe was assessed with MRI relaxivity measurement (T2 signal). Regarding the in vitro MRI relaxivity measurements outputs (r2=144.4), PVPMSFe can attenuate the T2 signal of MRI, perfectly which makes it an efficient T2 contrast agent.


Assuntos
Nanopartículas de Magnetita , Nanopartículas , Meios de Contraste , Nanopartículas Magnéticas de Óxido de Ferro , Imageamento por Ressonância Magnética , Dióxido de Silício , Espectroscopia de Infravermelho com Transformada de Fourier
11.
Braz. arch. biol. technol ; 64: e21210069, 2021. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1355792

RESUMO

Abstract Rhus coriaria, popularly known as sumac, has been used as a spice powder in the Middle East for centuries. It contains a broad range of naturally occurring compounds such as flavonoids, proteins, anthocyanins and volatile oils. It showed a putative importance in treatment of different disorders including cancers. In the current study, R. coriaria fruit extract was used for green synthesis of silver nanostructures (Ag-NSs) and their anticancer activity was tested against human breast cancer cells (MCF-7). The aqueous fruit extract was prepared. The synthesis of Ag-NSs under different conditions was optimized. The optimal reaction medium comprised 1:2 concentration of fruit extract and 3 mM concentration of silver nitrate solution. The green-synthesized Ag-NSs were confirmed by using UV-Visible spectroscopy at a range 300-700 nm, transmission electron microscopy (TEM), X-ray diffraction (XRD) and zeta potential measurements. The anti-proliferative activity of Ag-NSs was confirmed with inhibitory activity on MCF-7 cell line growth. The results showed that the IC50 values at 24 and 48h were 14.27 and 13.4 μg/ml, respectively. In conclusion the results of this study provide a simple, rapid, non-toxic and eco-friendly protocol for green-synthesis of Ag-NSs, which could be used as an alternative and interesting approach for safe and simple synthesis of Ag nanoparticles for biomedical uses.

12.
Heliyon ; 6(9): e04928, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32995618

RESUMO

Synthetic hydroxyapatite (HA) due to its high biocompatibility, anti-inflammatory properties, high stability, and a flexible structure in combination with magnetic nanoparticles has the strong potential to be used in modern medicine including tissue engineering, imaging, and drug delivery. Herein, a hydrothermal process was used to prepare magnetite nanoparticles dispersed on the hydroxyapatite nanorods with cetyltrimethylammonium bromide (CTAB) as a surfactant. Characterization study of the synthesized iron oxide-hydroxyapatite (IO-HA) nanocomposite was performed by FT-IR spectroscopy, X-ray powder diffraction, energy dispersive X-Ray analysis (EDX) for elemental mapping, transmission electron microscopy, and vibrating sample magnetometer. Then, the biocompatibility of the synthesized nanocomposite studied by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) assay and hemocompatibility assay. Focus on this point, curcumin loaded IO-HA (Cur@IO-HA) was developed for exploring the pH-sensitivity of the drug carrier and then evaluating its cellular uptake. The in vitro efficacy of the synthesized nanocomposites as a magnetic resonance imaging (MRI) contrast agent was also investigated. Our results showed that IO-HA nanocomposite is non-cytotoxic and hemocompatible as well as a good pH-sensitive drug carrier and a favorable MRI T2 contrast agent. Comparing to the free curcumin, Cur@IO-HA displayed a good cellular uptake. Taking into account the above issues, IO-HA nanocomposite has the most potential for application as a theranostic MRI contrast agent.

13.
Curr Drug Deliv ; 16(10): 923-930, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31663477

RESUMO

BACKGROUND: It has been shown that curcumin (Cur) has anti-plasmodial activity; however, its weak bioavailability, rapid metabolism, and limited chemical stability have restricted its application in clinical usages. Nanostructured lipid carriers (NLCs) are a type of Drug-Delivery Systems (DDSs) whose core matrix is composed of both solid and liquid lipids. OBJECTIVE: The aim of the current study was to prepare and characterize curcumin-loaded nanostructured lipid carriers (Cur-NLC) for malaria treatment. METHODS: For producing NLC, coconut oil and cetyl palmitate were selected as a liquid and solid lipid, respectively. In order to prepare the Cur-NLC, the microemulsion method was applied. General toxicity assay on Artemia salina as well as hemocompatibility was investigated. Anti-plasmodial activity was studied on mice infected with Plasmodium berghei. RESULTS: The NLCs mean particle size and Polydispersity Index (PI) were 145 nm and 0.3, respectively. Further, the zeta potential of the Cur-NLC was -25 mV. The NLCs indicated a pseudo-spherical shape observed via transmission electron microscopy (TEM). The loading capacity and encapsulation efficacy of the obtained Cur-NLC were 3.1 ± 0.015% and 74 ± 3.32%, respectively. In vitro, Cur release profiles showed a sustained-release pattern up to 5 days in the synthesized Cur-NLC. The results of in vivo antiplasmodial activity against P. berghei revealed that antimalarial activity of Cur-NLC was significantly higher compared with that of free Cur at the dose of 40 mg/kg/day. CONCLUSION: The results of this study suggested that NLC would be used as a potential nanocarrier for the treatment of malaria.


Assuntos
Antimaláricos/farmacologia , Curcumina/farmacologia , Lipídeos/química , Malária/tratamento farmacológico , Nanoestruturas/química , Plasmodium berghei/efeitos dos fármacos , Animais , Antimaláricos/química , Artemia/efeitos dos fármacos , Curcumina/química , Modelos Animais de Doenças , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Camundongos , Tamanho da Partícula , Propriedades de Superfície
14.
Mater Sci Eng C Mater Biol Appl ; 100: 771-780, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30948114

RESUMO

The blood brain barrier is a major obstacle to the entry of the majority of CNS-active agents. In the present research, the potential of magnetic polymeric micelles (MPMs) for brain-targeting of naproxen was evaluated. The MPMs were made of methoxy poly(ethyleneglycol)-poly (caprolactone) copolymer and super paramagnetic iron oxide nanoparticles (SPIONs). To investigate the impact of particle size on the in vivo biofate of nanoparticles, MPMs with two different sizes were prepared. The prepared magnetic polymeric micelles had diameters of 137 ±â€¯3.5 nm (MPM137) and 242 ±â€¯6.2 nm (MPM242) and their surface charges were about -6.5 and - 4.5 mV, respectively. Pharmacokinetic and biodistribution of nanoparticles were characterized in rats using an external magnet of 0.4 Tesla field strength located on the skull of anesthetized animals. Significant differences in volumes of central as well as peripheral compartments were observed between both MPM formulations and free naproxen solution. After 8 h of administration, the brain concentration of naproxen was shown to be higher in the case of MPM137 in comparison with MPM242 and free drug. The findings revealed that the polymeric magnetic micelles with diameters smaller than 150 nm could be initially considered as a promising carrier to improve therapeutic agent accumulation in the brain for the treatment of CNS diseases.


Assuntos
Encéfalo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Magnetismo , Micelas , Naproxeno/farmacologia , Naproxeno/farmacocinética , Polímeros/química , Animais , Liberação Controlada de Fármacos , Masculino , Nanopartículas/química , Nanopartículas/ultraestrutura , Naproxeno/administração & dosagem , Naproxeno/sangue , Tamanho da Partícula , Poliésteres/síntese química , Poliésteres/química , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Espectroscopia de Prótons por Ressonância Magnética , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Fatores de Tempo , Distribuição Tecidual/efeitos dos fármacos
15.
Toxicol Lett ; 278: 18-29, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28642010

RESUMO

This study aimed to evaluate bio-safety of magnetic chitosan nanogels as dual triggered drug carrier for doxorubicin through analysis of mitochondrial function. In the present study, chitosan/TPP nanogels containing magnetite nanoparticles (NPs) were prepared according to the ionotropic gelation method as novel pH-sensitive magnetic nanogels. The NPs showed outstanding entrapment efficiency for doxorubicin (76.6%) with a sustained and high extent of drug release in the acidic media (pH=5-7) compared to the neutral media. Various mitochondrial functional parameters including complex II activity, MDA amount, GSH level, membrane potential collapse, swelling, apoptosis and release of cytochrome c were used to investigate the bio-safety of the nanogels. The findings revealed that the extent of mitochondrial dysfunction of doxorubicin were in the order of free doxorubicin>doxorubicin loaded magnetic nanogels=>doxorubicin loaded Nanogels. The results also revealed that the nanogels and the magnetite nanogels seem to possess promising capability as a safe carrier in comparison of the toxic potential effect of free doxorubicin.


Assuntos
Antineoplásicos/toxicidade , Quitosana/toxicidade , Doxorrubicina/toxicidade , Portadores de Fármacos , Fígado/efeitos dos fármacos , Magnetismo/métodos , Nanopartículas de Magnetita/toxicidade , Mitocôndrias Hepáticas/efeitos dos fármacos , Nanomedicina/métodos , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Quitosana/química , Citocromos c/metabolismo , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Glutationa/metabolismo , Cinética , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Nanopartículas de Magnetita/química , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/patologia , Dilatação Mitocondrial/efeitos dos fármacos , Medição de Risco , Solubilidade , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Succinato Desidrogenase/metabolismo , Termogravimetria
16.
Mater Sci Eng C Mater Biol Appl ; 61: 665-73, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26838895

RESUMO

A conjugate of the NSAIDs drug, naproxen, with diblock methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) copolymer was synthesized by the reaction of copolymer with naproxen in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. The naproxen conjugated copolymers were characterized with different techniques including (1)HNMR, FTIR, and DSC. The naproxen conjugated mPEG-PCL copolymers were self-assembled into micelles in aqueous solution. The TEM analysis revealed that the micelles had the average size of about 80 nm. The release behavior of conjugated copolymer was investigated in two different media with the pH values of 7.4 and 5.2. In vitro release study showed that the drug release rate was dependant on pH as it was higher at lower pH compared to neutral pH. Another feature of the conjugated micelles was a more sustained release profile compared to the conjugated copolymer. The kinetic of the drug release from naproxen conjugated micelles under different values of pH was also investigated by different kinetic models such as first-order, Makoid-Banakar, Weibull, Logistic, and Gompertz.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Micelas , Naproxeno , Poliésteres , Polietilenoglicóis , Linhagem Celular , Humanos , Naproxeno/química , Naproxeno/farmacocinética , Naproxeno/farmacologia , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/farmacologia
17.
Int J Pharm ; 500(1-2): 62-76, 2016 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-26721723

RESUMO

In this study, the aim was to introduce and characterize a new trimodally-targeted nanomagnetic onco-theranostic system for simultaneous early diagnosis and efficient treatment of cancer. The onco-theranostic system was designed as it could target the tumor site through three targeting approach, i.e. magnetic, folic acid receptor, and pH sensitivity, and concurrently, due to the presence of superparamagnetic iron oxide nanoparticles (SPIONs) with super paramagnetic characteristics could be useful as MRI contrast agent for early cancer diagnosis. To achieve this goal, SPIONs were coated with chitosan and folic acid-conjugated chitosan via ionic gelation method in order to obtain non-targeted nanomagnetic onco-diagnostic (NT/NOD) and targeted nanomagnetic onco-diagnostic (T/NOD) systems. Finally, doxorubicin was loaded successfully into NT/NOD and T/NOD in order to obtain nanomagnetic onco-theranostic (NT/NOT) and targeted nanomagnetic onco-theranostic (T/NOT) systems. The entrapment efficiency and drug loading of T/NOT was determined to be 62.33 ± 5.20% and 10.26 ± 1.36%, respectively. MTT assay revealed that all systems were biocompatible within the concentration range investigated. Also, the T/NOT system showed the lowest IC50 comparing with free doxorubicin and NT/NOT system. In addition, uptake studies and competitive inhibition study verified the folate receptor mediated endocytosis of targeted system by MCF-7 as a folate receptor-positive cell line. The finding revealed that the extent of drug release from theranostic systems was pH-sensitive as it was higher at acidic media compared to that of in the neutral condition. Finally, T2-weighted phantom images, with an acceptable and dose-dependent resolution, proved the potential of T/NOT system as promising T2 MR contrast agent for diagnostic purpose. These finding proved that the prepared T/NOT system have great potential as a novel tumor-targeting nanotheranostic agent for simultaneous MRI imaging and treatment of folate receptor-positive cancers. Further studies are needed to test their behavior in vivo.


Assuntos
Transportadores de Ácido Fólico/metabolismo , Nanopartículas de Magnetita , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Composição de Medicamentos , Desenho de Fármacos , Liberação Controlada de Fármacos , Ácido Fólico/química , Humanos , Concentração de Íons de Hidrogênio , Hipertermia Induzida , Células MCF-7 , Fenômenos Magnéticos , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Camundongos , Células NIH 3T3 , Neoplasias/metabolismo , Nanomedicina Teranóstica
18.
Bioimpacts ; 5(3): 141-50, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26457252

RESUMO

INTRODUCTION: Expansion of efficacious theranostic systems is of pivotal significance for medicine and human healthcare. Magnetic nanoparticles (MNPs) are known as drug delivery system and magnetic resonance imaging (MRI) contrast agent. MNPs as drug carriers have attracted significant attention because of the delivery of drugs loaded onto MNPs to solid tumors, maintaining them in the target site by an external electromagnetic field, and subsequently releasing drugs in a controlled manner. On the other hand, it is believed that MNPs possess high potential as MRI contrast agents. The aim of this work was to payload curcumin into dextran coated MNPs and investigate their potential as theranostic systems for controlled drug delivery and MRI imaging. METHODS: MNPs were synthesized as a core and coated with dextran as polymeric shell to provide steric stabilization. Curcumin as anticancer drug was selected to be loaded into NPs. To characterize the synthesized NPs, various techniques (e.g., DLS, FESEM, FT-IR, XRD, and VSM) were utilized. In vitro drug release of curcumin was evaluated at 37˚C at the pH value of 5.4 and 7.4.The feasibility of employment of dextran coated MNPs as MRI contrast agents were also studied. RESULTS: Formulations prepared from dextran coated MNPs showed high loading (13%) and encapsulation efficiency (95%). In vitro release study performed in the phosphate-buffered saline (PBS, pH= 7.4, 5.4) revealed that the dextran coated MNPs possess sustained release behavior at least for 4 days with the high extent of drug release in acidic media. Vibrating sample magnetometer (VSM) analysis proved the superparamagnetic properties of the dextran coated MNPs with relatively high-magnetization value indicating that they were sufficiently sensitive to external magnetic fields as magnetic drug carriers. Furthermore, dextran coated MNPs exhibited high potential as T2 contrast agents for MRI. CONCLUSION: Based on our findings, we propose the dextran coated MNPs as promising nanosystem for the delivery of various drugs such as curcumin and MRI contrast agent.

19.
Daru ; 23: 45, 2015 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-26381740

RESUMO

BACKGROUND: Superparamagnetic iron oxide nanoparticles (SPIONs) are the most commonly used negative MRI contrast agent which affect the transverse (T2) relaxation time. The aim of the present study was to investigate the impact of various polymeric coatings on the performance of magnetite nanoparticles as MRI contrast agents. METHODS: Ferrofluids based on magnetite (Fe3O4) nanoparticles (SPIONs) were synthesized via chemical co-precipitation method and coated with different biocompatible polymer coatings including mPEG-PCL, chitosan and dextran. RESULTS: The bonding status of different polymers on the surface of the magnetite nanoparticles was confirmed by the Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). The vibrating sample magnetometer (VSM) analysis confirmed the superparamagnetic behavior of all synthesized nanoparticles. The field-emission scanning electron microscopy (FE-SEM) indicated the formation of quasi-spherical nanostructures with the final average particle size of 12-55 nm depending on the type of polymer coating, and X-ray diffraction (XRD) determined inverse spinel structure of magnetite nanoparticles. The ferrofluids demonstrated sufficient colloidal stability in deionized water with the zeta potentials of -24.2, -16.9, +31.6 and -21 mV for the naked SPIONs, and for dextran, chitosan and mPEG-PCL coated SPIONs, respectively. Finally, the magnetic relaxivities of water based ferrofluids were measured on a 1.5 T clinical MRI instrument. The r2/r1 value was calculated to be 17.21, 19.42 and 20.71 for the dextran, chitosan and mPEG-PCL coated SPIONs, respectively. CONCLUSIONS: The findings demonstrated that the value of r2/r1 ratio of mPEG-PCL modified SPIONs is higher than that of some commercial contrast agents. Therefore, it can be considered as a promising candidate for T2 MRI contrast agent.


Assuntos
Meios de Contraste/química , Nanopartículas de Magnetita/química , Polímeros/química , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/ultraestrutura , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
20.
Adv Pharm Bull ; 5(1): 115-20, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25789228

RESUMO

PURPOSE: This paper evaluates the impact of cross linking strategy on the characteristics of magnetic chitosan nanogels (MCNs) as targeted drug delivery system for doxorubicin. METHODS: Sodium tripolyphosphate (TPP) and glutaraldehyde were used as physical (electrostatic) and chemical (covalent binding) cross-linker agents, respectively. MCNs were characterized by means of X-ray diffraction (XRD), Scanning electron microscopy (SEM), fourier transform infrared (FT-IR) spectroscopy and vibrating sample magnetometer (VSM). Scanning electron microscopy (SEM) indicated the formation of spherical nanostructures with the final average particle size of around 35-40 nm. RESULTS: The finding proved the superparamagnetic properties of the MCNs with relatively high-magnetization values which indicate that the MCNs were enough sensitive to external magnetic fields as a magnetic drug carrier. To understand the differences between the drug delivery properties of chemically and physically cross linked MCNs, the drug release studies were also conducted. Altogether, the results of this study clearly indicate that, however, both MCNs exhibited sustained drug release behaviour, the chemically cross linked MCNs provided enhanced controlled drug release characteristics in comparison to physically cross linked MCNs. Besides, according to the drug release behaviour of MCNs in buffer solutions in two different medium with the pH values of 5.3 and 7.4, it was clear that both nanoparticles exhibited pH sensitivity where the extent of drug release in the acidic media was significantly higher than neutral media. CONCLUSION: It can be concluded that chemically cross linked MCNs may serve as an ideal carrier for stimuli-triggered and controlled anticancer drug delivery.

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