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      A swarm of slippery micropropellers penetrates the vitreous body of the eye

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          Abstract

          A swarm of microrobots propels through the vitreous humor of the eye and reaches a small targeted spot on the retina.

          Abstract

          The intravitreal delivery of therapeutic agents promises major benefits in the field of ocular medicine. Traditional delivery methods rely on the random, passive diffusion of molecules, which do not allow for the rapid delivery of a concentrated cargo to a defined region at the posterior pole of the eye. The use of particles promises targeted delivery but faces the challenge that most tissues including the vitreous have a tight macromolecular matrix that acts as a barrier and prevents its penetration. Here, we demonstrate novel intravitreal delivery microvehicles—slippery micropropellers—that can be actively propelled through the vitreous humor to reach the retina. The propulsion is achieved by helical magnetic micropropellers that have a liquid layer coating to minimize adhesion to the surrounding biopolymeric network. The submicrometer diameter of the propellers enables the penetration of the biopolymeric network and the propulsion through the porcine vitreous body of the eye over centimeter distances. Clinical optical coherence tomography is used to monitor the movement of the propellers and confirm their arrival on the retina near the optic disc. Overcoming the adhesion forces and actively navigating a swarm of micropropellers in the dense vitreous humor promise practical applications in ophthalmology.

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          Most cited references 42

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          Global data on visual impairment in the year 2002.

          This paper presents estimates of the prevalence of visual impairment and its causes in 2002, based on the best available evidence derived from recent studies. Estimates were determined from data on low vision and blindness as defined in the International statistical classification of diseases, injuries and causes of death, 10th revision. The number of people with visual impairment worldwide in 2002 was in excess of 161 million, of whom about 37 million were blind. The burden of visual impairment is not distributed uniformly throughout the world: the least developed regions carry the largest share. Visual impairment is also unequally distributed across age groups, being largely confined to adults 50 years of age and older. A distribution imbalance is also found with regard to gender throughout the world: females have a significantly higher risk of having visual impairment than males. Notwithstanding the progress in surgical intervention that has been made in many countries over the last few decades, cataract remains the leading cause of visual impairment in all regions of the world, except in the most developed countries. Other major causes of visual impairment are, in order of importance, glaucoma, age-related macular degeneration, diabetic retinopathy and trachoma.
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            Controlled propulsion of artificial magnetic nanostructured propellers.

            For biomedical applications, such as targeted drug delivery and microsurgery, it is essential to develop a system of swimmers that can be propelled wirelessly in fluidic environments with good control. Here, we report the construction and operation of chiral colloidal propellers that can be navigated in water with micrometer-level precision using homogeneous magnetic fields. The propellers are made via nanostructured surfaces and can be produced in large numbers. The nanopropellers can carry chemicals, push loads, and act as local probes in rheological measurements.
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              Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues.

              Mucus is a viscoelastic and adhesive gel that protects the lung airways, gastrointestinal (GI) tract, vagina, eye and other mucosal surfaces. Most foreign particulates, including conventional particle-based drug delivery systems, are efficiently trapped in human mucus layers by steric obstruction and/or adhesion. Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on anatomical location, thereby strongly limiting the duration of sustained drug delivery locally. A number of debilitating diseases could be treated more effectively and with fewer side effects if drugs and genes could be more efficiently delivered to the underlying mucosal tissues in a controlled manner. This review first describes the tenacious mucus barrier properties that have precluded the efficient penetration of therapeutic particles. It then reviews the design and development of new mucus-penetrating particles that may avoid rapid mucus clearance mechanisms, and thereby provide targeted or sustained drug delivery for localized therapies in mucosal tissues.
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                Author and article information

                Journal
                Sci Adv
                Sci Adv
                SciAdv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                November 2018
                02 November 2018
                : 4
                : 11
                Affiliations
                [1 ]Max Planck Institute for Intelligent Systems, Heisenbergstrasse 3, 70569 Stuttgart, Germany.
                [2 ]Key Laboratory of Microsystems and Microstructures Manufacturing, Ministry of Education, Harbin Institute of Technology, Yi Kuang Jie 2, Harbin 150080, China.
                [3 ]Institute of Physical Chemistry, University of Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
                [4 ]Max Planck Institute for Medical Research, Jahnstraße 29, 69120 Heidelberg, Germany.
                [5 ]Center of Ophthalmology, University Eye Hospital Tübingen, Tübingen, Germany.
                [6 ]Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, Denmark.
                Author notes
                [* ]Corresponding author. Email: qiu@ 123456is.mpg.de (T.Q.); fischer@ 123456is.mpg.de (P.F.)
                Article
                aat4388
                10.1126/sciadv.aat4388
                6214640
                Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                Funding
                Funded by: doi http://dx.doi.org/10.13039/100005156, Alexander von Humboldt-Stiftung;
                Funded by: doi http://dx.doi.org/10.13039/501100000781, European Research Council;
                Award ID: 278213
                Categories
                Research Article
                Research Articles
                SciAdv r-articles
                Applied Sciences and Engineering
                Applied Sciences and Engineering
                Custom metadata
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