Tailoring magnetic PLGA nanoparticles suitable for doxorubicin delivery

One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells, which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale-based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an external magnetic field. Thus, the drug can be carried to the targeted site safely. The aim of this study is to prepare poly(dl-lactic-co-glycolic acid) (PLGA)-coated magnetic nanoparticles and load anti-cancer drug, doxorubicin to them. For this purpose, magnetite (Fe3O4) iron oxide nanoparticles were synthesized as a magnetic core material (MNP) and then coated with oleic acid. Oleic acid-coated MNP (OA-MNP) was encapsulated into PLGA. Effects of different OA-MNP/PLGA ratios on magnetite entrapment efficiency were investigated. Doxorubicin-loaded magnetic polymeric nanoparticles (DOX-PLGA-MNP) were prepared. After the characterization of prepared nanoparticles, their cytotoxic effects on MCF-7 cell line were studied. PLGA-coated magnetic nanoparticles (PLGA-MNP) had a proper size and superparamagnetic character. The highest magnetite entrapment efficiency of PLGA-MNP was estimated as 63 % at 1:8 ratio. Cytotoxicity studies of PLGA-MNP did not indicate any notable cell death between the concentration ranges of 2 and 125 mu g/ml. Drug loading efficiency was estimated as 32 %, and it was observed that DOX-PLGA-MNP showed significant cytotoxicity on MCF-7 cells compared to PLGA-MNP. The results showed that prepared nanoparticles have desired size and superparamagnetic characteristics without serious toxic effects on cells. These nanoparticles may be suitable for targeted drug delivery applications

Tailoring the magnetic behavior of polymeric particles for bioapplications

In this study, magnetic polymeric nanoparticles were prepared use in for targeted drug delivery. First, iron oxide (Fe3O4) magnetic nanoparticles (MNPs) were synthesized by coprecipitation with ferrous and ferric chloride salts. Then, to render the MNPs hydrophobic, the surfaces were covered with oleic acid. Finally, the hydrophobic MNPs (H-MNPs) were encapsulated with polymer. The emulsion evaporation technique was used for the preparation of polymer-coated H-MNP. Poly(DL-lactide-co-glycolide) (PLGA) and chitosan-modified PLGA were used as polymers. The polymeric nanoparticles were characterized and compared. X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, small-angle X-ray scattering, size distribution, zeta potential, magnetic properties, and magnetite entrapment efficiency measurements were performed to investigate the properties of the nanoparticles. The XTT assay was performed to understand the biocompatibility (i.e., toxicity) of MNPs and magnetic polymeric nanoparticles to MCF-7 cells

Mineralized peptide nanofiber gels for enhanced osteogenic differentiation

\u3cp\u3eMineral deposition is observed in both bacterial and eukaryotic organisms through a broad range of mechanisms. Both organic and inorganic components play crucial roles in the formation of mineralized tissues, and acidic proteins are particularly important in this context owing to their ability to stimulate nucleation of minerals. Here, we present negatively-charged self-assembling peptide amphiphile molecules as a template to nucleate calcium phosphate mineralization in a bioactive scaffold environment. Acidic peptide molecules were shown to induce formation of hydroxyapatite like calcium phosphate mineralization, which was characterized by scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, X-ray diffractometry, oscillatory rheology and atomic force microscopy. The osteoblast-like cells were found to reveal enhanced osteogenic differentiation on pre-mineralized peptide nanofiber networks, suggesting that mineral deposition can be used as a means of enhancing the bioactivity of peptide-based scaffold systems.\u3c/p\u3

Engineering anisotropic cardiac monolayers on microelectrode arrays for non-invasive analyses of electrophysiological properties

A standard culture of cardiac cells as unorganized monolayers on tissue culture plastic or glass does not recapitulate the architectural or the mechanical properties of native myocardium. We investigated the physical and protein cues from the extracellular matrix to engineer anisotropic cardiac tissues as highly aligned monolayers on top of the microelectrode array (MEA). The MEA platform allows non-invasive measurement of beating rate and conduction velocity. The effect of different extracellular proteins was tested by using the most common extracellular matrix proteins in the heart, fibronectin and gelatin, after aligning myocytes using a microcontact (μC) printing technique. Both proteins showed similar electrophysiological results before the monolayer began to delaminate after the sixth day of culture. Additionally, there were no significant differences on day 4 between the two microcontact printed proteins in terms of sarcomere alignment and gap junction expression. To test the effect of substrate stiffness, a micromolded (μM) gelatin hydrogel was fabricated in different concentrations (20% and 2%), corresponding to the elastic moduli of approximately 33 kPa and 0.7 kPa, respectively, to cover both spectra of the in vivo range of myocardium. Cardiac monolayers under micromolded conditions beat in a much more synchronized fashion, and exhibited conduction velocity that was close to the physiological value. Both concentrations of gelatin hydrogel conditions yielded similar sarcomere alignment and gap junction expression on day 4 of culture. Ultimately, the 3D micromolded gelatin hydrogel that recapitulated myocardial stiffness improved the synchronicity and conduction velocity of neonatal rat ventricular myocytes (NRVM) without any stimulation. Identifying such microenvironmental factors will lead to future efforts to design heart on a chip platforms that mimic in vivo environment and predict potential cardiotoxicity when testing new drugs

Idarubicin-loaded folic acid conjugated magnetic nanoparticles as a targetable drug delivery system for breast cancer

WOS: 000342668300008PubMed ID: 25194441Conventional 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 transforminfrared 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 0-500 mu g/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. (C) 2014 Elsevier Masson SAS. All rights reserved.TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TBAG-109T949]This study was supported by TUBITAK (TBAG-109T949)