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      A Novel Nanoparticle Mediated Selective Inner Retinal Photocoagulation for Diseases of the Inner Retina

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          Abstract

          <p class="first" id="P1">A novel nanoparticle mediated methodology for laser photocoagulation of the inner retina to achieve tissue selective treatment is presented. </p><div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d4640285e119">Methods</h5> <p id="P2">Transport of 527 nm, 577 nm, and 810 nm laser, heat deposition and eventual thermal damage in vitreous, retina, RPE, choroid and sclera were modelled using Bouguer-Beer-Lambert law of absorption and solved numerically using the finite volume method. Nanoparticles were designed using Mie theory of scattering. Performance of the new photocoagulation strategy using gold nanospheres and gold-silica nanoshells was compared to that of conventional methods without nanoparticles. For experimental validation, vitreous cavity of <i>ex vivo</i> porcine eyes was infused with gold nanospheres. After ~6 hours of nanoparticle diffusion, the porcine retina was irradiated with a green laser and imaged simultaneously using a spectral domain optical coherence tomography (Spectralis SD-OCT, Heidelberg Engineering). </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <h5 class="section-title" id="d4640285e127">Results</h5> <p id="P3">Our computational model predicted a significant spatial shift in the peak temperature from RPE to the inner retinal region when infused with nanoparticles. Arrhenius thermal damage in the mid-retinal location was achieved in ~14 ms for 527 nm laser thereby reducing the irradiation duration by ~30 ms compared to treatment without nanoparticles. In <i>ex vivo</i> porcine eyes infused with gold nanospheres, SD-OCT retinal images revealed a lower thermal damage and expansion at RPE due to laser photocoagulation. </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <h5 class="section-title" id="d4640285e135">Conclusion</h5> <p id="P4">Nanoparticle infused laser photocoagulation strategy provided a selective inner retinal thermal damage with significant decrease in laser power and laser exposure time. </p> </div><div class="section"> <a class="named-anchor" id="S4"> <!-- named anchor --> </a> <h5 class="section-title" id="d4640285e140">Significance</h5> <p id="P5">The proposed treatment strategy shows possibilities for an efficient and highly selective inner retinal laser treatment. </p> </div>

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          Most cited references72

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          Ocular drug delivery.

          Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases.
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            Nanoshell-enabled photonics-based imaging and therapy of cancer.

            Metal nanoshells are a novel type of composite spherical nanoparticle consisting of a dielectric core covered by a thin metallic shell which is typically gold. Nanoshells possess highly favorable optical and chemical properties for biomedical imaging and therapeutic applications. By varying the relative the dimensions of the core and the shell, the optical resonance of these nanoparticles can be precisely and systematically varied over a broad region ranging from the near-UV to the mid-infrared. This range includes the near-infrared (NIR) wavelength region where tissue transmissivity peaks. In addition to spectral tunability, nanoshells offer other advantages over conventional organic dyes including improved optical properties and reduced susceptibility to chemical/thermal denaturation. Furthermore, the same conjugation protocols used to bind biomolecules to gold colloid are easily modified for nanoshells. In this article, we first review the synthesis of gold nanoshells and illustrate how the core/shell ratio and overall size of a nanoshell influences its scattering and absorption properties. We then describe several examples of nanoshell-based diagnostic and therapeutic approaches including the development of nanoshell bioconjugates for molecular imaging, the use of scattering nanoshells as contrast agents for optical coherence tomography (OCT), and the use of absorbing nanoshells in NIR thermal therapy of tumors.
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              Nanocarriers, such as nanoparticles, have the capacity to deliver ocular drugs to specific target sites and hold promise to revolutionize the therapy of many eye diseases. Results to date strongly suggest that ocular medicine will benefit enormously from the use of this nanometric scale technology. One of the most important handicaps of the eye as a target organ for drugs is the presence of several barriers that impede direct and systemic drug access to the specific site of action. Superficial barriers include the ocular surface epithelium and the tear film, and internal barriers include the blood-aqueous and blood-retina barriers. Topical application is the preferred route for most drugs, even when the target tissues are at the back part of the eye where intraocular injections are currently the most common route of administration. Direct administration using any of these two routes faces many problems related to drug bioavailability, including side effects and repeated uncomfortable treatments to achieve therapeutic drug levels. In this regard, the advantages of using nanoparticles include improved topical passage of large, poorly water-soluble molecules such as glucocorticoid drugs or cyclosporine for immune-related, vision-threatening diseases. Other large and unstable molecules, such as nucleic acids, delivered using nanoparticles offer promising results for gene transfer therapy in severe retinal diseases. Also, nanoparticle-mediated drug delivery increases the contact time of the administered drug with its target tissue, such as in the case of brimonidine, one of the standard treatments for glaucoma, or corticosteroids used to treat autoimmune uveitis, a severe intraocular inflammatory process. In addition, nanocarriers permit the non-steroidal anti-inflammatory drug indomethacin to reach inner eye structures using the transmucosal route. Finally, nanoparticles allow the possibility of targeted delivery to reach specific types of cancer, such as melanoma, leaving normal cells untouched. This review summarizes experimental results from our group and others since the beginnings of nanocarrier technology to deliver drugs to different locations in the eye. Also, it explores the future possibilities of nanoparticles not only as drug delivery systems but also as aides for diagnostic purposes. Copyright © 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                IEEE Transactions on NanoBioscience
                IEEE Trans.on Nanobioscience
                Institute of Electrical and Electronics Engineers (IEEE)
                1536-1241
                1558-2639
                October 2017
                October 2017
                : 16
                : 7
                : 542-554
                Article
                10.1109/TNB.2017.2741490
                5926191
                28829313
                0f313933-d1f7-4a9f-9c26-a060a5a67f67
                © 2017
                History

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