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      Self-Assembled Mucin-Containing Microcarriers via Hard Templating on CaCO 3 Crystals

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          Abstract

          Porous vaterite crystals of CaCO 3 are extensively used for the fabrication of self-assembled polymer-based microparticles (capsules, beads, etc.) utilized for drug delivery and controlled release. The nature of the polymer used plays a crucial role and discovery of new perspective biopolymers is essential to assemble microparticles with desired characteristics, such as biocompatibility, drug loading efficiency/capacity, release rate, and stability. Glycoprotein mucin is tested here as a good candidate to assemble the microparticles because of high charge due to sialic acids, mucoadhesive properties, and a tendency to self-assemble, forming gels. Mucin loading into the crystals via co-synthesis is twice as effective as via adsorption into preformed crystals. Desialylated mucin has weaker binding to the crystals most probably due to electrostatic interactions between sialic acids and calcium ions on the crystal surface. Improved loading of low-molecular-weight inhibitor aprotinin into the mucin-containing crystals is demonstrated. Multilayer capsules (mucin/protamine) 3 have been made by the layer-by-layer self-assembly. Interestingly, the deposition of single mucin layers (mucin/water) 3 has also been proven, however, the capsules were unstable, most probably due to additional (to hydrogen bonding) electrostatic interactions in the case of the two polymers used. Finally, approaches to load biologically-active compounds (BACs) into the mucin-containing microparticles are discussed.

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          Most cited references57

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          Mucin structure, aggregation, physiological functions and biomedical applications

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            The biology of mucus: Composition, synthesis and organization.

            In this review we discuss mucus, the viscoelastic secretion from goblet or mucous producing cells that lines the epithelial surfaces of all organs exposed to the external world. Mucus is a complex aqueous fluid that owes its viscoelastic, lubricating and hydration properties to the glycoprotein mucin combined with electrolytes, lipids and other smaller proteins. Electron microscopy of mucosal surfaces reveals a highly convoluted surface with a network of fibers and pores of varying sizes. The major structural and functional component, mucin is a complex glycoprotein coded by about 20 mucin genes which produce a protein backbone having multiple tandem repeats of Serine, Threonine (ST repeats) where oligosaccharides are covalently O-linked. The N- and C-terminals of this apoprotein contain other domains with little or no glycosylation but rich in cysteines leading to dimerization and further multimerization via SS bonds. The synthesis of this complex protein starts in the endoplasmic reticulum with the formation of the apoprotein and is further modified via glycosylation in the cis and medial Golgi and packaged into mucin granules via Ca2+ bridging of the negative charges on the oligosaccharide brush in the trans Golgi. The mucin granules fuse with the plasma membrane of the secretory cells and following activation by signaling molecules release Ca2+ and undergo a dramatic change in volume due to hydration of the highly negatively charged polymer brush leading to exocytosis from the cells and forming the mucus layer. The rheological properties of mucus and its active component mucin and its mucoadhesivity are briefly discussed in light of their importance to mucosal drug delivery.
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              Stimuli-responsive LbL capsules and nanoshells for drug delivery.

              Review of basic principles and recent developments in the area of stimuli responsive polymeric capsules and nanoshells formed via layer-by-layer (LbL) is presented. The most essential attributes of the LbL approach are multifunctionality and responsiveness to a multitude of stimuli. The stimuli can be logically divided into three categories: physical (light, electric, magnetic, ultrasound, mechanical, and temperature), chemical (pH, ionic strength, solvent, and electrochemical) and biological (enzymes and receptors). Using these stimuli, numerous functionalities of nanoshells have been demonstrated: encapsulation, release including that inside living cells or in tissue, sensors, enzymatic reactions, enhancement of mechanical properties, and fusion. This review describes mechanisms and basic principles of stimuli effects, describes progress in the area, and gives an outlook on emerging trends such as theranostics and nanomedicine. Copyright © 2011. Published by Elsevier B.V.
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                Author and article information

                Journal
                Micromachines (Basel)
                Micromachines (Basel)
                micromachines
                Micromachines
                MDPI
                2072-666X
                19 June 2018
                June 2018
                : 9
                : 6
                : 307
                Affiliations
                [1 ]Department of Chemistry, Lomonosov Moscow State University, Leninskiye Gory 1-3, 119991 Moscow, Russia; nbalab2008@ 123456gmail.com (N.G.B.); sholina-katya@ 123456mail.ru (E.A.S.); luboff.filatova@ 123456gmail.com (L.Y.F.)
                [2 ]Federal Research and Clinical Centre of Physical-Chemical Medicine, Malaya Pirogovskaya, 1A, 119992 Moscow, Russia; lemik2007@ 123456yandex.ru
                [3 ]Nottingham Trent University, School of Science and Technology, Clifton Lane, Nottingham NG11 8NS, UK; anna.vikulina@ 123456ntu.ac.uk
                Author notes
                [* ]Correspondence: dmitry.volodkin@ 123456ntu.ac.uk ; Tel.: +44-115-848-3140
                Author information
                https://orcid.org/0000-0001-9427-2055
                https://orcid.org/0000-0001-7474-5329
                Article
                micromachines-09-00307
                10.3390/mi9060307
                6187553
                299fdbed-cc19-4e02-a3c5-95ce85747df7
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 May 2018
                : 11 June 2018
                Categories
                Article

                caco3,mucin,adsorption,co-synthesis,layer-by-layer,protamine,aprotinin

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