Sugar-Mediated Disassembly of Mucin/Lectin Multilayers and Their Use as pH-Tolerant, On-Demand Sacrificial Layers

Abstract

The layer-by-layer (LbL) assembly of thin films on surfaces has proven to be an extremely useful technology for uses ranging from optics to biomedical applications. Releasing these films from the substrate to generate so-called free-standing multilayer films opens a new set of applications. Current approaches to generating such materials are limited because they can be cytotoxic, difficult to scale up, or have undesirable side reactions on the material. In this work, a new sacrificial thin film system capable of chemically triggered dissolution at physiological pH of 7.4 is described. The film was created through LbL assembly of bovine submaxillary mucin (BSM) and the lectin jacalin (JAC) for a (BSM/JAC) multilayer system, which remains stable over a wide pH range (pH 3-9) and at high ionic strength (up to 5 M NaCl). This stability allows for subsequent LbL assembly of additional films in a variety of conditions, which could be released from the substrate by incubation in the presence of a competitive inhibitor sugar, melibiose, which selectively disassembles the (BSM/JAC) section of the film. This novel multilayer system was then applied to generate free-standing, 7 μm diameter, circular ultrathin films, which can be attached to a cell surface as a "backpack". A critical thickness of about 100 nm for the (BSM/JAC) film was required to release the backpacks from the glass substrate, after incubation in melibiose solution at 37 °C for 1 h. Upon their release, backpacks were subsequently attached to murine monocytes without cytotoxicity, thereby demonstrating the compatibility of this mucin-based release system with living cells.

Covalently-crosslinked mucin biopolymer hydrogels for sustained drug delivery

“…a b s t r a c t 27 The sustained delivery of both hydrophobic and hydrophilic drugs from hydrogels has remained a chal- 28 lenge requiring the design and scalable production of complex multifunctional synthetic polymers. Here, 29 we demonstrate that mucin glycoproteins, the gel-forming constituents of native mucus, are suitable for 30 assembly into robust hydrogels capable of facilitating the sustained release of hydrophobic and hydrophi- 31 lic drugs.…”

“…109 To most effectively harness the properties of mucin to bind and 110 release drugs, the mucin must first be assembled into a material 111 that is easily handled and that leaves its biophysical properties 112 intact. Mucin-based biomaterials in the form of thin films have 113 been assembled layer-by-layer, complexing mucin with lysozymes 114 [23], chitosan [24,25], or lectins [26,27]. Microparticles composed 115 of mucin-alginate [28] or mucin-gelatin [29] complexes also have 116 been created.…”

Macrophages with cellular backpacks for targeted drug delivery to the brain

“…At the interface between the glass slide and the assembled multilayer construct is a “release region” which can dissolve upon incubation with the sugar, melibiose. We had previously developed this as a simple and benign means to releasing backpacks from their substrates [18]. Atop this sacrificial film, we deposited a “magnetic region” to aid in purification of cell backpacks, confer film rigidity and potentially serve as an imaging agent [19–22].…”

Laser surface structuring affects polymer deposition, coating homogeneity, and degradation rate of Mg alloys

“…LbL was selected as it provided nm to μm thicknesses [15][16][17], and coating complex microstructured surfaces in a conformable way [18]. The used primer layer allowed protection of the Mg alloy substrate from in-process degradation during the LbL dip coating phase.…”