Nanotechnology for ocular therapeutics and tissue repair

Raju, Hemalatha B.; Goldberg, Jeffrey L.

doi:10.1586/17469899.3.4.431

Cited by 33 publications

(15 citation statements)

References 28 publications

(15 reference statements)

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“…As such particles may prove to be excellent delivery vehicles for gene, drug or cellular delivery [1], understanding their interaction with ocular tissues will continue to be an important part of moving them towards potential therapeutic use.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Magnetic Micro- and Nanoparticle Toxicity to Ocular Tissues

Raju

Vedula

et al. 2011

PLoS ONE

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PurposeMagnetic nanoparticles (MNPs) may be used for focal delivery of plasmids, drugs, cells, and other applications. Here we ask whether such particles are toxic to ocular structures.MethodsTo evaluate the ocular toxicity of MNPs, we asked if either 50 nm or 4 µm magnetic particles affect intraocular pressure, corneal endothelial cell count, retinal morphology including both cell counts and glial activation, or photoreceptor function at different time points after injection. Sprague-Dawley rats (n = 44) were injected in the left eye with either 50 nm (3 µl, 1.65 mg) or 4 µm (3 µl, 1.69 mg) magnetic particles, and an equal volume of PBS into the right eye. Electroretinograms (ERG) were used to determine if MNPs induce functional changes to the photoreceptor layers. Enucleated eyes were sectioned for histology and immunofluorescence.ResultsCompared to control-injected eyes, MNPs did not alter IOP measurements. ERG amplitudes for a-waves were in the 100–250 µV range and b-waves were in the 500–600 µV range, with no significant differences between injected and non-injected eyes. Histological sectioning and immunofluorescence staining showed little difference in MNP-injected animals compared to control eyes. In contrast, at 1 week, corneal endothelial cell numbers were significantly lower in the 4 µm magnetic particle-injected eyes compared to either 50 nm MNP- or PBS-injected eyes. Furthermore, iron deposition was detected after 4 µm magnetic particle but not 50 nm MNP injection.ConclusionsIntravitreal or anterior chamber injections of MNPs showed little to no signs of toxicity on retinal structure, photoreceptor function or aqueous drainage in the eye. Our results suggest that MNPs are safe for intraocular use.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Magnetic Micro- and Nanoparticle Toxicity to Ocular Tissues

Raju

Vedula

et al. 2011

PLoS ONE

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“…Other obstacles facing treatment of ocular infections include patient incompliance, difficulty to maintain the required dose at site of action, and the limited transcorneal permeation of applied drugs [7]. Therefore, nanosuspensions could be a more suitable drug delivery system for the ocular route of administration [8]. Ocular nanosized drug delivery systems protect the ocular-instilled drugs from metabolism by tear fluid enzymes and increase their permeation through corneal membranes [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Modeling, Optimization, and In Vitro Corneal Permeation of Chitosan-Lomefloxacin HCl Nanosuspension Intended for Ophthalmic Delivery

et al. 2015

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Lomefloxacin HCl (LF) is a widely used fourthgeneration fluoroquinolone antibiotic. Like most drug solutions administered via ocular route, it is usually eliminated by eye protective mechanisms. Chitosan (CS) is a natural polysaccharide polymer with numerous advantages in ocular delivery with, antibacterial, and antifungal properties. The aims were to formulate and optimize LF nanosuspensions (NS) with enhanced antimicrobial activity and prolonged duration using ionic gelation technique. Formulation variables included drug load, CS concentration, crosslinker type (tripolyphosphate and sodium alginate), and concentration. Nanosuspension properties (particle size, zeta potential, polydispersity index, entrapment efficiency, drug release, and permeation through bovine cornea) were evaluated. The artificial neural networks (ANNs) model showed optimum entrapment efficiency of 70.63 % w/w, particle size of 176±0.28 nm, and zeta potential of 13.65 mV. Transmission electron microscopy illustrated the production of well-defined spherical nanoparticles. The nanosuspensions showed prolonged release of LF for more than 8 h and threefold increase in amount permeated through bovine cornea compared to drug solution. Improved antibacterial activity of the nanosuspension was noted where 2-and 3.5-fold decrease in minimum inhibitory concentration (MIC) of drug against Gram-positive and Gram-negative bacteria were observed, respectively. Twofold decrease in minimum bactericidal concentration (MBC) of drug nanosuspension against both types of bacteria was also demonstrated. Histopathological examination showed compatibility of optimized formulation with eye tissues in rabbit model. Therefore, model-optimized LF nanosuspension could be an ideal solution to ocular infections by virtue of their augmented activity, high compatibility, and improved permeability.

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“…Nanomaterials are currently used clinically to augment the potency of prostate cancer therapy, to enhance imaging modalities, and to improve drug bioavailability, among other applications. 24–30 Nanoparticle drug delivery systems have been designed to target drugs and genes to specific tissues, to evade the immune system, and to study subcellular biological processes. 31–36 Recently, magnetic nanoparticles have also been explored to deliver cell therapies throughout the body.…”

Section: Discussionmentioning

confidence: 99%

Magnetic field-guided cell delivery with nanoparticle-loaded human corneal endothelial cells

Moysidis

Álvarez-Delfín

Peschansky

et al. 2015

Nanomedicine: Nanotechnology, Biology and Medicine

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To improve the delivery and integration of cell therapy using magnetic cell guidance for replacement of corneal endothelium, here we assess magnetic nanoparticles’ (MNPs) effects on human corneal endothelial cells (HCECs) in vitro. Biocompatible, 50 nm superparamagnetic nanoparticles endocytosed by cultured HCECs induced no short- or long-term change in viability or identity. Assessment of guidance of the magnetic HCECs in the presence of different magnet shapes and field strengths showed a 2.4-fold increase in delivered cell density compared to gravity alone. After cell delivery, HCECs formed a functional monolayer, with no difference in tight junction formation between MNP-loaded and control HCECs. These data suggest that nanoparticle-mediated magnetic cell delivery may increase the efficiency of cell delivery without compromising HCEC survival, identity or function. Future studies may assess the safety and efficacy of this therapeutic modality in vivo.

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Nanotechnology for ocular therapeutics and tissue repair

Cited by 33 publications

References 28 publications

Evaluation of Magnetic Micro- and Nanoparticle Toxicity to Ocular Tissues

Evaluation of Magnetic Micro- and Nanoparticle Toxicity to Ocular Tissues

Modeling, Optimization, and In Vitro Corneal Permeation of Chitosan-Lomefloxacin HCl Nanosuspension Intended for Ophthalmic Delivery

Magnetic field-guided cell delivery with nanoparticle-loaded human corneal endothelial cells

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