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      Drug Design, Development and Therapy (submit here)

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      Preparation and characterization of 6-mercaptopurine-coated magnetite nanoparticles as a drug delivery system


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          Iron oxide nanoparticles are of considerable interest because of their use in magnetic recording tape, ferrofluid, magnetic resonance imaging, drug delivery, and treatment of cancer. The specific morphology of nanoparticles confers an ability to load, carry, and release different types of drugs.

          Methods and results

          We synthesized superparamagnetic nanoparticles containing pure iron oxide with a cubic inverse spinal structure. Fourier transform infrared spectra confirmed that these Fe 3O 4 nanoparticles could be successfully coated with active drug, and thermogravimetric and differential thermogravimetric analyses showed that the thermal stability of iron oxide nanoparticles coated with chitosan and 6-mercaptopurine (FCMP) was markedly enhanced. The synthesized Fe 3O 4 nanoparticles and the FCMP nanocomposite were generally spherical, with an average diameter of 9 nm and 19 nm, respectively. The release of 6-mercaptopurine from the FCMP nanocomposite was found to be sustained and governed by pseudo-second order kinetics. In order to improve drug loading and release behavior, we prepared a novel nanocomposite (FCMP-D), ie, Fe 3O 4 nanoparticles containing the same amounts of chitosan and 6-mercaptopurine but using a different solvent for the drug. The results for FCMP-D did not demonstrate “burst release” and the maximum percentage release of 6-mercaptopurine from the FCMP-D nanocomposite reached about 97.7% and 55.4% within approximately 2,500 and 6,300 minutes when exposed to pH 4.8 and pH 7.4 solutions, respectively. By MTT assay, the FCMP nanocomposite was shown not to be toxic to a normal mouse fibroblast cell line.


          Iron oxide coated with chitosan containing 6-mercaptopurine prepared using a coprecipitation method has the potential to be used as a controlled-release formulation. These nanoparticles may serve as an alternative drug delivery system for the treatment of cancer, with the added advantage of sparing healthy surrounding cells and tissue.

          Most cited references67

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          Chitosan microspheres as a potential carrier for drugs.

          Chitosan is a biodegradable natural polymer with great potential for pharmaceutical applications due to its biocompatibility, high charge density, non-toxicity and mucoadhesion. It has been shown that it not only improves the dissolution of poorly soluble drugs but also exerts a significant effect on fat metabolism in the body. Gel formation can be obtained by interactions of chitosans with low molecular counterions such as polyphosphates, sulphates and crosslinking with glutaraldehyde. This gelling property of chitosan allows a wide range of applications such as coating of pharmaceuticals and food products, gel entrapment of biochemicals, plant embryo, whole cells, microorganism and algae. This review is an insight into the exploitation of the various properties of chitosan to microencapsulate drugs. Various techniques used for preparing chitosan microspheres and evaluation of these microspheres have also been reviewed. This review also includes the factors that affect the entrapment efficiency and release kinetics of drugs from chitosan microspheres.
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            Pseudo-second-order model for lead ion sorption from aqueous solutions onto palm kernel fiber.

            The sorption of lead ion onto palm kernel fiber was studied by performing batch kinetic sorption experiments. The batch sorption model, based on a pseudo-second-order mechanism, was applied to predict the rate constant of sorption, the equilibrium capacity and the initial sorption rate with the effects of the initial solution pH and fiber dose. Equilibrium concentrations were evaluated with the equilibrium capacity obtained from the pseudo-second-order rate equation. In addition, pseudo-isotherms were also obtained by changing fiber doses using the equilibrium concentration and equilibrium capacity obtained based on the pseudo-second-order constants.
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              Preparation and characterization of protein-loaded N-trimethyl chitosan nanoparticles as nasal delivery system.

              In this study, the potential of N-trimethyl chitosan (TMC) nanoparticles as a carrier system for the nasal delivery of proteins was investigated. TMC nanoparticles were prepared by ionic crosslinking of TMC solution (with or without ovalbumin) with tripolyphosphate, at ambient temperature while stirring. The size, zeta-potential and morphology of the nanoparticles were investigated as a function of the preparation conditions. Protein loading, protein integrity and protein release were studied. The toxicity of the TMC nanoparticles was tested by ciliary beat frequency measurements of chicken embryo trachea and in vitro cytotoxicity assays. The in vivo uptake of FITC-albumin-loaded TMC nanoparticles by nasal epithelia tissue in rats was studied by confocal laser scanning microscopy. The nanoparticles had an average size of about 350 nm and a positive zeta-potential. They showed a loading efficiency up to 95% and a loading capacity up to 50% (w/w). The integrity of the entrapped ovalbumin was preserved. Release studies showed that more than 70% of the protein remained associated with the TMC nanoparticles for at least 3 h on incubation in PBS (pH 7.4) at 37 degrees C. Cytotoxicity tests with Calu-3 cells showed no toxic effects of the nanoparticles, whereas a partially reversible cilio-inhibiting effect on the ciliary beat frequency of chicken trachea was observed. In vivo uptake studies indicated the transport of FITC-albumin-associated TMC nanoparticles across the nasal mucosa. In conclusion, TMC nanoparticles are a potential new delivery system for transport of proteins through the nasal mucosa.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Dove Medical Press
                25 September 2013
                : 7
                : 1015-1026
                [1 ]Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology, Selangor, Malaysia
                [2 ]Vaccines and Immunotherapeutics Laboratory, Selangor, Malaysia
                [3 ]Physics Department, Faculty of Science, Selangor, Malaysia
                [4 ]Chemical Pathology Unit, Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia
                Author notes
                Correspondence: Mohd Zobir bin Hussein, Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia, Tel +603 8946 8092, Fax +603 8943 8470, Email mzobir@ 123456upm.edu.my
                © 2013 Dorniani et al, publisher and licensee Dove Medical Press Ltd

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Original Research

                Pharmacology & Pharmaceutical medicine
                superparamagnetic nanoparticles,6-mercaptopurine,controlled release,cytotoxicity,drug delivery


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