Self-Assembled Mucin-Containing Microcarriers via Hard Templating on CaCO3 Crystals

Abstract

Porous vaterite crystals of CaCO3 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.

Layer-By-Layer Assemblies of Biopolymers: Build-Up, Mechanical Stability and Molecular Dynamics

“…Particularly, LbL technology presented several advantages for biomedicine: (i) deposition of homogeneous films with controlled thickness, (ii) high loading capacities and controlled release of biomolecules/drugs of various nature, and (iii) coating stability under physiological conditions. This made the LbL method one of the most rapidly growing strategies for generating thin film coatings of biomedical scaffolds [ 3 , 4 , 5 , 6 ], patterned surfaces [ 7 , 8 ], medical devices [ 9 , 10 ], implants [ 11 , 12 ], and a range of alternate bioapplications ( Figure 1 ); while multilayer capsules became promising nano- and micro-carriers for drug delivery applications [ 1 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”

Naturally derived nano- and micro-drug delivery vehicles: halloysite, vaterite and nanocellulose

“…ethylenediaminetetraacetic or citric acid). CaCO 3 -templated multilayer capsules are very promising delivery vehicles; their potential for drug delivery has been widely investigated, [96][97][98][99] this also includes in vitro 97 and in vivo studies. 98 This article does not consider VCC-templated capsules and beads; 100 for these topics the reader can refer to reviews 101 and 102.…”

“…113 Similarly, VCC crystals loaded with glucose oxidase and Fe 3 O 4 have been proposed for chemodynamic therapy via the ultrasound-assisted Fenton reaction. 114 In view of the high promise of VCC employment in mucosal drug delivery, 99,115 a recent report demonstrated an in vivo study of intranasal delivery into the brain using VCC pre-loaded with an anesthetic drug. 79 Interestingly, VCC crystals of different sizes ranging from nano-to micro-dimensions have been probed in this study, demonstrating that the micron-sized crystals ensure a more prolonged anesthetic effect than the nano-sized ones, while both are suitable carriers for intranasal delivery.…”

Polyelectrolyte Multilayer Capsule (PEMC)-Based Scaffolds for Tissue Engineering

“…Another approach has been introduced to load small drugs (even below 1 kDa) via the pre-loading of vaterite CaCO 3 crystals with a high-molecular-weight molecule that has a good affinity to the small drug in question. These hybrid crystals can be used to form PEMCs with desired properties [ 181 ]. An example includes the loading of doxorubicin into vaterite crystals pre-loaded with mucin ( Figure 8 ).…”