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1.
Int J Pharm ; 655: 124024, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38537920

RESUMEN

Controlling the drug release and restricting its presence in healthy organs is extremely valuable. In this study, mesoporous silica nanoparticles (MSN) as the core, loaded with paclitaxel (PTX), were coated with a non-porous silica shell functionalized with disulfide bonds. The nanoparticles were further coated with polyethylene glycol (PEG) via disulfide linkages. We analyzed the physicochemical properties of nanoparticles, including hydrodynamic size via Dynamic Light Scattering (DLS), zeta potential, X-ray Diffraction (XRD) patterns, Fourier-Transform Infrared (FTIR) spectra, and imaging through Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). The drug release profile in two distinct glutathione (GSH) concentrations of 2 µM and 10 µM was measured. The cellular uptake of nanoparticles by MCF-7 cell line was determined using Confocal Laser Scanning Microscopy (CLSM) images and flow cytometry. Furthermore, the cell viability and the capability of nanoparticles to induce apoptosis in MCF-7 cell line were studied using the MTT assay and flow cytometry, respectively. Our investigations revealed that the release of PTX from the drug delivery system was redox-responsive. Also, results indicated an elevated level of cellular uptake and efficient induction of apoptosis, underscoring the promising potential of this redox-responsive drug delivery system for breast cancer therapy.


Asunto(s)
Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Dióxido de Silicio/química , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Polietilenglicoles/química , Glutatión/química , Oxidación-Reducción , Disulfuros , Portadores de Fármacos/química , Porosidad
2.
Int J Pharm ; 646: 123495, 2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37806507

RESUMEN

In this study, surface modified mesoporous silica nanoparticles (MSNs) were prepared for the targeted delivery of the anticancer agents, daunorubicin (DNR) and cytarabine (CTR), against K562 leukemia cancer cell lines. The MSNs were surface-modified with pH-sensitive chitosan (CS) to prevent the burst release of anticancer agents at the physiological pH of 7.4 and to enable a higher drug release at lower pH and higher concentration of glutathione. Finally, the MSNs were surface modified with KK1B10 aptamer (Apt) to enhance their uptake by K562 cells through ligand-receptor interactions. The MSNs were characterized using different methods and both in vitro and in vivo experiments were utilized to demonstrate their suitability as targeted anticancer agents. The resultant MSNs exhibited an average particle size of 295 nm, a surface area of 39.06 m2/g, and a cumulative pore volume of 0.09 cm3/g. Surface modification of MSNs with chitosan (CS) resulted in a more regulated and acceptable continuous release rate of DNR. The drug release rate was significantly higher at pH 5 media enriched with glutathione, compared to pH 7.4. Furthermore, MSNs coated with CS and conjugated with aptamer (MSN-DNR + CTR@CS-Apt) exhibited a lower IC50 value of 2.34 µg/ml, compared to MSNs without aptamer conjugation, which displayed an IC50 value of 12.27 µg/ml. The results of the cell cycle analysis indicated that the administration of MSN-DNR + CTR@CS-Apt led to a significant increase in the population of apoptotic cells in the sub-G1 phase. Additionally, the treatment arrested the remaining cells in various other phases of the cell cycle. Furthermore, the interactions between Apt-receptors were found to enhance the uptake of MSNs by cancer cells. The results of in vivo studies demonstrated that the administration of MSN-DNR + CTR@CS-Apt led to a significant reduction in the expression levels of CD71 and CD235a markers, as compared to MSN-DNR + CTR@CS (p < 0.001). In conclusion, the surface modified MSNs prepared in this study showed lower IC50 against cancer cell lines and higher anticancer activity in animal models.


Asunto(s)
Antineoplásicos , Quitosano , Leucemia , Nanopartículas , Animales , Daunorrubicina , Quitosano/química , Citarabina , Dióxido de Silicio/química , Antineoplásicos/química , Nanopartículas/química , Glutatión , Porosidad , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/química
3.
Iran J Pharm Res ; 21(1): e130474, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36915404

RESUMEN

Background: Stimuli-responsive drug delivery systems have been proven to be a promising strategy to enhance tumor localization, overcome multidrug resistance (MDR), and reduce the side effects of chemotherapy agents. Objectives: In this study, a temperature and redox dual stimuli-responsive system using mesoporous silica nanoparticles (MSNs) for targeted delivery of doxorubicin (DOX) was developed. Methods: Mesoporous silica nanoparticles were capped with poly(N-isopropylacrylamide) (PNIPAM), a thermo-sensitive polymer, with atom transfer radical polymerization (ATRP) method, via disulfide bonds (DOX-MSN-S-S-PNIPAM) to attain a controlled system that releases DOX under glutathione-rich (GSH-rich) environments and temperatures above PNIPAM's lower critical solution temperature (LCST). Morphological and physicochemical properties of the nanoparticles were indicated using transmission electron microscopy (TEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Brunauer-Emmett-Teller (BET). The drug release tests were performed at 25°C and 41°C in the absence and presence of the DTT, and the obtained results confirmed the synergic effect of temperature and reductive agent on a dual responsive release profile with a 73% cumulative release at 41°C and reductive environment during 240 min. Results: The average loaded drug content and encapsulation efficacy were reported as 42% and 29.5% at the drug: nanoparticle ratio of 1.5: 1. In vitro cytotoxicity assays on MCF-7 cell lines indicated significant viability decreased in cells exposed to DOX-MSN-S-S-PNIPAM compared to the free drug (DOX). Conclusions: Based on the results, DOX-MSN-S-S-PNIPAM has shown much more efficiency with stimuli-responsive properties in comparison to DOX on MCF-7 cancer cell lines.

4.
Daru ; 28(1): 171-180, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32006342

RESUMEN

Rod-like mesoporous silica nanoparticles with pH-responsive amphiphilic hyperbranched polyester shells were prepared for doxorubicin (DOX) delivery. First, rod-shaped mesoporous silica nanoparticles (MSNs) were obtained, then hydrophobic hyperbranched polyester Boltorn H40 (H40) was grafted on their surface. The H40 coated MSNs were next treated with amine-functionalized polyethylene glycol (PEG) to achieve the hydrophilic and pH-responsive material denoted as PEG-H40-MSNs. The experimental results showed that PEG-H40-MSNs were successfully synthesized. BET analysis showed that rod MSNs exhibits a type IV standard isotherm. TEM revealed that the thin gray polymer layer was formed around the SBA-15 particle with a diameter of around 150 nm. DOX was effectively loaded, which can be released according to the ambient pH inside the cell as follow: at pH 7.4, only 9.7% of the DOX was released after 48 h; as the pH decreased to 5.5, the cumulative release reached to 49% at the same time. PEG-H40-MSNs showed less than 1.6% of hemolytic activity and a slight effect on the liver and kidney of treated mice were observed at a high disposal dosage implying negligible toxicities were caused by PEG-H40-MSNs in both in vitro hemolysis analysis and in vivo biochemical in mice. However, the in vitro cytotoxicity evaluation of the DOX-PEG-H40-MSNs showed that the cell cytotoxicity of both pure DOX and DOX-loaded PEG-H40-MSNs generally enhanced by increasing the concentration of DOX. Graphical abstract Schematic of cellular uptake and DOX release of PEG-H40-MSNs nanoparticle.


Asunto(s)
Antibióticos Antineoplásicos , Doxorrubicina , Portadores de Fármacos , Nanopartículas , Polietilenglicoles , Dióxido de Silicio , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/química , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Liberación de Fármacos , Eritrocitos/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Células MCF-7 , Masculino , Ratones Endogámicos BALB C , Nanopartículas/administración & dosificación , Nanopartículas/química , Polietilenglicoles/administración & dosificación , Polietilenglicoles/química , Dióxido de Silicio/administración & dosificación , Dióxido de Silicio/química
5.
Ultrason Sonochem ; 39: 144-152, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28732931

RESUMEN

pH-responsive magnetic carriers at the nanoscale are one of the most important agents for the targeted treatment of cancer. In this study, Fe3O4 nanoparticles were prepared by co-precipitation method and functionalized with three types of PEG using ultrasound waves. PEGlated particles were modified with chitosan shell through ultrasound-assisted double emulsion method. The prepared material which was used as a pH responsive carrier for pinpointed 5-FU delivery. The chemico-physical properties of prepared nanoparticles have been investigated. Results demonstrated that pure Fe3O4 had a mean diameter of 20nm with the regular spherical shape which was increased after modification step depending on the type of PEG. 5-FU loading properties and releasing behaviors studies in different pHs which showed that 5-FU can be efficiently loaded in the Fe3O4@Cs-PEG. Also, in the case of release, the amount of 5-FU released at pH=5.8 is noticeably higher compared to the released amount at pH=7.4 in all three samples at any distinct time. For instance at pH=7.4, 27% of the 5-FU was released from the Fe3O4@Cs-PEG2 during 48h; as the pH decreases to 5.8, the cumulative amount of 5-FU released enhanced to 52%. The in vitro MTT assay results demonstrated that the cell viability decreases in all synthesized nanoparticles as the pH medium of MCF-7 culture became to 5.8. For example, cell viability of Fe3O4@Cs-sPEG decreased from 44±2% to 36±1.9% at a concentration of 5 (µg/ml) as the pH varied from 7.4 to 5.8.


Asunto(s)
Quitosano/química , Portadores de Fármacos/química , Portadores de Fármacos/síntesis química , Fluorouracilo/química , Nanopartículas de Magnetita/química , Polietilenglicoles/química , Ondas Ultrasónicas , Supervivencia Celular/efectos de los fármacos , Técnicas de Química Sintética , Liberación de Fármacos , Fluorouracilo/farmacología , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7
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