RESUMEN
Conventional cancer chemotherapies cannot differentiate between healthy and cancer cells, and lead to severe side effects and systemic toxicity. Another major problem is the drug resistance development before or during the treatment. In the last decades, different kinds of controlled drug delivery systems have been developed to overcome these shortcomings. The studies aim targeted drug delivery to tumor site. Magnetic nanoparticles (MNP) are potentially important in cancer treatment since they can be targeted to tumor site by an externally applied magnetic field. In this study, MNPs were synthesized, covered with biocompatible polyethylene glycol (PEG) and conjugated with folic acid. Then, anti-cancer drug idarubicin was loaded onto the nanoparticles. Shape, size, crystal and chemical structures, and magnetic properties of synthesized nanoparticles were characterized. The characterization of synthesized nanoparticles was performed by dynamic light scattering (DLS), Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM) analyses. Internalization and accumulation of MNPs in MCF-7 cells were illustrated by light and confocal microscopy. Empty MNPs did not have any toxicity in the concentration ranges of 0-500µg/mL on MCF-7 cells, while drug-loaded nanoparticles led to significant toxicity in a concentration-dependent manner. Besides, idarubicin-loaded MNPs exhibited higher toxicity compared to free idarubicin. The results are promising for improvement in cancer chemotherapy.
Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias de la Mama/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Ácido Fólico/administración & dosificación , Idarrubicina/administración & dosificación , Nanopartículas de Magnetita/administración & dosificación , Antineoplásicos/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Femenino , Ácido Fólico/metabolismo , Humanos , Idarrubicina/metabolismo , Células MCF-7RESUMEN
BACKGROUND: In recent years nano-sized dendrimer/hyperbranched polymers gained importance in drug delivery applications. OBJECTIVE: In this study, a novel fatty acid-based hyperbranched resin (HBR) was synthesized and used for tamoxifen (TAM) and idarubicin (IDA) delivery. METHODS: The core of the HBR was dipentaerythritol, and the branching was provided by dimethylolpropionic acid. The molecule was terminated by ricinoleic acid. Chemical and structural characterization of the resin was carried out and then drug-loading experiments were performed. CONCLUSION: The loading efficiencies were found to be 73.3% for TAM and 74% for IDA. The Fourier transform infrared spectroscopy analysis showed that TAM physically bounded onto the resin whereas IDA interacted chemically. Controlled release in phosphate buffer was improved by Pseudomonas sp. lipase and sodium dodecyl sulfate. The release rates decreased with the increase of loading concentrations. The cytotoxicity analyses were carried out on MCF-7 breast cancer cells for both drug-free and drug-loaded HBR. Drug-free particles did not have significant toxicity. Drug-loaded nanoparticles caused higher levels of cell death than pure drugs.
Asunto(s)
Antineoplásicos/administración & dosificación , Portadores de Fármacos , Ácidos Grasos , Idarrubicina/administración & dosificación , Nanopartículas , Polímeros , Tamoxifeno/administración & dosificación , Antineoplásicos/uso terapéutico , Neoplasias de la Mama , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/uso terapéutico , Dendrímeros/síntesis química , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Idarrubicina/uso terapéutico , Lipasa/metabolismo , Ácidos Ricinoleicos/química , Tamoxifeno/uso terapéuticoRESUMEN
Immersion of electrospun polycaprolactone (PCL) nanofiber mats in calcium phosphate solutions similar to simulated body fluid resulted in deposition of biomimetic calcium phosphate layer on the nanofibers and thus a highly bioactive novel scaffold has been developed for bone tissue engineering. Coatings with adequate integrity, favorable chemistry and morphology were achieved in less than 6h of immersion. In the coating solutions, use of lower concentrations of phosphate sources with respect to the literature values (i.e., 3.62 vs. 10 mM) was substantiated by a thermodynamic modeling approach. Recipe concentration combinations that were away from the calculated dicalcium phosphate phase stability region resulted in micron-sized calcium phosphates with native nanostructures. While the nano/microstructure formed by the deposited calcium phosphate layer is controlled by increasing the solution pH to above 6.5 and increasing the duration of immersion experimentally, the nanostructure imposed by the dimensions of the fibers was controlled by the polymer concentration (12% w/v), applied voltage (25 kV) and capillary tip to collector distance (35 cm). The deposited coating increased quantitatively by extending the soak up to 6h. On the other hand, the porosity values attained in the scaffolds were around 87% and the biomimetic coatings did not alter the nanofiber mat porosities negatively since the deposition continued along the fibers after the first 2h. Upon confirming the non-toxic nature of the electrospun PCL nanofiber mats, the effects of different nano/microstructures formed were evaluated by the osteoblastic activity. The levels of both alkaline phosphatase activity and osteocalcin were found to be higher in the coated PCL nanofibers than in the uncoated PCL nanofibers, indicating that biomimetic calcium phosphate on PCL nanofibers supports osteoblastic differentiation.