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1.  Magnetic Nanoparticles as Intraocular Drug Delivery System to Target Retinal Pigmented Epithelium (RPE) 
One of the most challenging efforts in drug delivery is the targeting of the eye. The eye structure and barriers render this organ poorly permeable to drugs. Quite recently the entrance of nanoscience in ocular drug delivery has improved the penetration and half-life of drugs, especially in the anterior eye chamber, while targeting the posterior chamber is still an open issue. The retina and the retinal pigment epithelium/choroid tissues, located in the posterior eye chamber, are responsible for the majority of blindness both in childhood and adulthood. In the present study, we used magnetic nanoparticles (MNPs) as a nanotool for ocular drug delivery that is capable of specific localization in the retinal pigmented epithelium (RPE) layer. We demonstrate that, following intraocular injection in Xenopus embryos, MNPs localize specifically in RPE where they are retained for several days. The specificity of the localization did not depend on particle size and surface properties of the MNPs used in this work. Moreover, through similar experiments in zebrafish, we demonstrated that the targeting of RPE by the nanoparticles is not specific for the Xenopus species.
PMCID: PMC3907888  PMID: 24451140
magnetic nanoparticle (MNP); intraocular delivery; retinal pigmented epithelium (RPE); Xenopus laevis
2.  Generation of Magnetized Olfactory Ensheathing Cells for Regenerative Studies in the Central and Peripheral Nervous Tissue 
As olfactory receptor axons grow from the peripheral to the central nervous system (CNS) aided by olfactory ensheathing cells (OECs), the transplantation of OECs has been suggested as a plausible therapy for spinal cord lesions. The problem with this hypothesis is that OECs do not represent a single homogeneous entity, but, instead, a functionally heterogeneous population that exhibits a variety of responses, including adhesion and repulsion during cell-matrix interactions. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical gradients. In this paper, we report a system based on modified OECs carrying magnetic nanoparticles as a proof of concept experiment enabling specific studies aimed at exploring the potential of OECs in the treatment of spinal cord injuries. Our studies have confirmed that magnetized OECs (i) survive well without exhibiting stress-associated cellular responses; (ii) in vitro, their migration can be modulated by magnetic fields; and (iii) their transplantation in organotypic slices of spinal cord and peripheral nerve showed positive integration in the model. Altogether, these findings indicate the therapeutic potential of magnetized OECs for CNS injuries.
PMCID: PMC3709706  PMID: 23708092
nerve regeneration; olfactory ensheathing cell; magnetic nanoparticle; organotypic culture
3.  Poly-l-lysine-coated magnetic nanoparticles as intracellular actuators for neural guidance 
It has been proposed in the literature that Fe3O4 magnetic nanoparticles (MNPs) could be exploited to enhance or accelerate nerve regeneration and to provide guidance for regenerating axons. MNPs could create mechanical tension that stimulates the growth and elongation of axons. Particles suitable for this purpose should possess (1) high saturation magnetization, (2) a negligible cytotoxic profile, and (3) a high capacity to magnetize mammalian cells. Unfortunately, the materials currently available on the market do not satisfy these criteria; therefore, this work attempts to overcome these deficiencies.
Magnetite particles were synthesized by an oxidative hydrolysis method and characterized based on their external morphology and size distribution (high-resolution transmission electron microscopy [HR-TEM]) as well as their colloidal (Z potential) and magnetic properties (Superconducting QUantum Interference Devices [SQUID]). Cell viability was assessed via Trypan blue dye exclusion assay, cell doubling time, and MTT cell proliferation assay and reactive oxygen species production. Particle uptake was monitored via Prussian blue staining, intracellular iron content quantification via a ferrozine-based assay, and direct visualization by dual-beam (focused ion beam/scanning electron microscopy [FIB/SEM]) analysis. Experiments were performed on human neuroblastoma SH-SY5Y cell line and primary Schwann cell cultures of the peripheral nervous system.
This paper reports on the synthesis and characterization of polymer-coated magnetic Fe3O4 nanoparticles with an average diameter of 73 ± 6 nm that are designed as magnetic actuators for neural guidance. The cells were able to incorporate quantities of iron up to 2 pg/cell. The intracellular distribution of MNPs obtained by optical and electronic microscopy showed large structures of MNPs crossing the cell membrane into the cytoplasm, thus rendering them suitable for magnetic manipulation by external magnetic fields. Specifically, migration experiments under external magnetic fields confirmed that these MNPs can effectively actuate the cells, thus inducing measurable migration towards predefined directions more effectively than commercial nanoparticles (fluidMAG-ARA supplied by Chemicell). There were no observable toxic effects from MNPs on cell viability for working concentrations of 10 μg/mL (EC25 of 20.8 μg/mL, compared to 12 μg/mL in fluidMAG-ARA). Cell proliferation assays performed with primary cell cultures of the peripheral nervous system confirmed moderate cytotoxicity (EC25 of 10.35 μg/mL).
These results indicate that loading neural cells with the proposed MNPs is likely to be an effective strategy for promoting non-invasive neural regeneration through cell magnetic actuation.
PMCID: PMC3394465  PMID: 22811603
magnetic nanoparticle; actuator; migration; neural regeneration
4.  Magnetically-triggered Nanocomposite Membranes: a Versatile Platform for Triggered Drug Release 
Nano letters  2011;11(3):1395-1400.
Drug delivery devices based on nanocomposite membranes containing thermoresponsive nanogels and superparamagnetic nanoparticles have been demonstrated to provide reversible, on-off drug release upon application (and removal) of an oscillating magnetic field. We show that the dose of drug delivered across the membrane can be tuned by engineering the phase transition temperature of the nanogel, the loading density of nanogels in the membrane, and the membrane thickness, allowing for on-state delivery of model drugs over at least two orders of magnitude (0.1–10 µg/hr). The zero-order kinetics of drug release across the membranes permit drug doses from a specific device to be tuned according to the duration of the magnetic field. Drugs over a broad range of molecular weights (500–40,000 Da) can be delivered by the same membrane device. Membrane-to-membrane and cycle-to-cycle reproducibility is demonstrated, suggesting the general utility of these membranes for drug delivery.
PMCID: PMC3065496  PMID: 21344911
Iron oxide; nanogel; nanoparticles; triggered drug release; on-demand; superparamagnetism
5.  The influence of colloidal parameters on the specific power absorption of PAA-coated magnetite nanoparticles 
Nanoscale Research Letters  2011;6(1):383.
The suitability of magnetic nanoparticles (MNPs) to act as heat nano-sources by application of an alternating magnetic field has recently been studied due to their promising applications in biomedicine. The understanding of the magnetic relaxation mechanism in biocompatible nanoparticle systems is crucial in order to optimize the magnetic properties and maximize the specific absorption rate (SAR). With this aim, the SAR of magnetic dispersions containing superparamagnetic magnetite nanoparticles bio-coated with polyacrylic acid of an average particle size of ≈10 nm has been evaluated separately by changing colloidal parameters such as the MNP concentration and the viscosity of the solvent. A remarkable decrease of the SAR values with increasing particle concentration and solvent viscosity was found. These behaviours have been discussed on the basis of the magnetic relaxation mechanisms involved.
PACS: 80; 87; 87.85jf
PMCID: PMC3211476  PMID: 21711915
6.  A Magnetically-Triggered Composite Membrane for On-Demand Drug Delivery 
Nano letters  2009;9(10):3651-3657.
Nanocomposite membranes based on thermosensitive, poly(N-isopropylacrylamide)-based nanogels and magnetite nanoparticles have been designed to achieve “on-demand” drug delivery upon the application of an oscillating magnetic field. On-off release of sodium fluorescein over multiple magnetic cycles has been successfully demonstrated using prototype membrane-based devices. The total drug dose delivered was directly proportional to the duration of the “on” pulse. The membranes were non-cytotoxic, biocompatible, and retained their switchable flux properties after 45 days of subcutaneous implantation.
PMCID: PMC2761986  PMID: 19736912

Results 1-6 (6)