Preparation and in-vitro evaluation of doxorubicin-loaded Fe3O4 magnetic nanoparticles modified with biocompatible copolymer

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
International Journal of Nanomedicine (Impact Factor: 4.38). 02/2012; 7:511-26. DOI: 10.2147/IJN.S24326
Source: PubMed


Superparamagnetic iron oxide nanoparticles are attractive materials that have been widely used in medicine for drug delivery, diagnostic imaging, and therapeutic applications. In our study, superparamagnetic iron oxide nanoparticles and the anticancer drug, doxorubicin hydrochloride, were encapsulated into poly (D, L-lactic-co-glycolic acid) poly (ethylene glycol) (PLGA-PEG) nanoparticles for local treatment. The magnetic properties conferred by superparamagnetic iron oxide nanoparticles could help to maintain the nanoparticles in the joint with an external magnet.
A series of PLGA:PEG triblock copolymers were synthesized by ring-opening polymerization of D, L-lactide and glycolide with different molecular weights of polyethylene glycol (PEG(2000), PEG(3000), and PEG(4000)) as an initiator. The bulk properties of these copolymers were characterized using (1)H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy, and differential scanning calorimetry. In addition, the resulting particles were characterized by x-ray powder diffraction, scanning electron microscopy, and vibrating sample magnetometry.
The doxorubicin encapsulation amount was reduced for PLGA:PEG(2000) and PLGA:PEG(3000) triblock copolymers, but increased to a great extent for PLGA:PEG(4000) triblock copolymer. This is due to the increased water uptake capacity of the blended triblock copolymer, which encapsulated more doxorubicin molecules into a swollen copolymer matrix. The drug encapsulation efficiency achieved for Fe(3)O(4) magnetic nanoparticles modified with PLGA:PEG(2000), PLGA:PEG(3000), and PLGA:PEG(4000) copolymers was 69.5%, 73%, and 78%, respectively, and the release kinetics were controlled. The in vitro cytotoxicity test showed that the Fe(3)O(4)-PLGA:PEG(4000) magnetic nanoparticles had no cytotoxicity and were biocompatible.
There is potential for use of these nanoparticles for biomedical application. Future work includes in vivo investigation of the targeting capability and effectiveness of these nanoparticles in the treatment of lung cancer.

Download full-text


Available from: Amin Barkhordari, Mar 21, 2014
  • Source
    • "Experiments involving the endoprotease furin demonstrated that monomers crossed-linked with furin-cleavable peptides could form nanocapsules designed to only be degraded by this enzyme and release the therapeutically active drug, after entering the cells by endocytosis (Biswas et al., 2011). Finally, antibodies can be attached to the particles surface to bind selectively to specific receptors, improving the biocompatibility of synthetic polymers and increasing the drug delivery efficiency (Akbarzadeh et al., 2012). One problem related with these approaches is that after being inside the cells, the proteins are entrapped inside endosomes and, eventually, are degraded in lysosomes and cleared out of the cells (Biswas et al. 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: This chapter reviews the most significant discovers in biomaterial-based systems for drug delivery in the last decades. Biomaterials have been explored as drug delivery systems in medicine since the mid-1960’s and, almost half a century later, incessant advances in basic sciences, engineering, medicine and pharmaceutical sciences led to the development of new biomaterials and improvement of the existing ones. Many materials, much as lipids, proteins, polysaccharides and also polyester polymers are successfully used as encapsulation materials. Recent works focus their attention on the arrangement of different biomacromolecules and biomaterials for enhancing the properties of the drug delivery systems. Advantages in controlled drug release, targeting delivery and more flexibility and in vivo stability have been demonstrated with these new materials. Finally, adaptation of “smart” materials to the biological conditions and modification of cells and lipid bilayers interactions also increased the drug nanocarriers’ applications in medical field.
    Biomaterials of Nanotechnology, Edited by J.N. Govil, 01/2014: chapter 5: pages 484; Studium Press LLC., ISBN: 1-626990-11-5
  • Source
    • "QDs may be advantageous because administration of a QDs formulation is non-invasive and eliminates the need for a biopsy. QDs toxicity, however, remains a major concern for clinical applications [43] [44] [45] [46] [47] [48] [49]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This review describes the state of art in nanoparticle and nanodevice applications for medical diagnosis and disease treatment. Nanodevices, such as cantilevers, have been integrated into high-sensitivity disease marker diagnostic detectors and devices, are stable over long periods of time, and display reliable performance properties. Nanotechnology strategies have been applied to therapeutic purposes as well. For example, nanoparticle-based delivery systems have been developed to protect drugs from degradation, thereby reducing the required dose and dose frequency, improving patient comfort and convenience during treatment, and reducing treatment expenses. The main objectives for integrating nanotechnologies into diagnostic and therapeutic applications in the context of intestinal diseases are reviewed.
    Digestive and Liver Disease 05/2013; 45(12). DOI:10.1016/j.dld.2013.03.019 · 2.96 Impact Factor
  • Source
    • "[28] [29] Therefore, a site-specific and targeted DDS is essential to overcome these problems in the effective treatment of cancers using Dox as an anticancer agent. Application of liposomes,[30] [31] hydrogels,[32] microspheres,[33] polymeric micelles,[34] drug-polymer conjugates,[35] magnetic nanoparticles [36] [37] and nanofibrous scaffolds [38] [39] have been reported in literature. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In this study, stimuli-responsive nanofibers (NFs) were successfully prepared via electrospinning method. Poly(N-isopropylacrylamide-co-acrylamide-co-vinylpyrrolidone) P(NIPAAM-AAm-VP) was used as the material for preparing the electrospinning NFs. Doxorubicin (Dox)-loaded NFs were prepared and characterized by XRD, Scanning electron microscopy and FTIR. A response surface methodology was used to evaluate the effect of key parameters on the fiber diameter. The cytotoxicity of Dox-loaded NFs was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole assay on lung cancer A549 cell lines. In vitro cytotoxicity assay showed that the P(NIPAAM-AAm-VP) fibers themselves did not affect the growth of A549 cells. Antitumor activity of the Dox-loaded fibers against the cells was kept over the whole experimental process, while that of pristine Dox disappeared within 48 h. Drug release pattern from these systems is in zero order and drug release rate is not dependent on drug/polymer ratio in different implant formulations. These novel NFs were stable and preserved their morphology even after incubation in release medium (pH 7.4, 37 °C), while collapsed and dispersed quickly in aqueous solution of acidic medium at room. The reported incorporation of stimuli-responsive properties into NFs takes advantage of their extremely large surface area and porosity and is expected to provide a simple platform for smart drug delivery.
    Designed Monomers & Polymers 02/2013; 16(6). DOI:10.1080/15685551.2013.771303 · 2.78 Impact Factor
Show more