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.
1 June 2019 in Journal of Colloid and Interface Science
Porous vaterite CaCO3 crystals are widely used as containers for drug loading and as sacrificial templates to assemble polymer-based nano- and micro-particles at mild conditions. Special attention is paid nowadays to mucosal delivery where the glycoprotein mucin plays a crucial role as a main component of a mucous. In this work mucoadhesive properties of vaterite crystals have been tested by investigation of mucin binding to the crystals as a function of (i) time, (ii) glycoprotein concentration, (iii) adsorption conditions and (iv) degree of mucin desialization. Mucin adsorption follows Bangham equation indicating that diffusion into crystal pores is the rate-limiting step. Mucin strongly binds to the crystals (ΔG = -35 ± 4 kJ mol-1) via electrostatic and hydrophobic interactions forming a gel and thus giving the tremendous mucin mass content in the crystals of up to 16%. Despite strong intermolecular mucin-mucin interactions, pure mucin spheres formed after crystal dissolution are unstable. However, introduction of protamine, actively used for mucosal delivery, makes the spheres stable via additional electrostatic bonding. The results of this work indicate that the vaterite crystals are extremely promising carriers for mucosal drug delivery and for development of test-systems for the analysis of the mucoadhesion.
It is shown by the methods of precision tensiometry, quasi-elastic light scattering, and UV, IR, and fluorescent spectroscopies that the properties of binary aqueous solutions with a constant concentration of bovine serum albumin and different concentrations of the nonionic surfactant Tween 80 (1 × 10–7−6 × 10−2 M) are determined mainly by the complexation and formation of a new phase. The complexation occurs owing to specific interactions (hydrogen bonding) between polar groups of Tween 80 and protein molecules. The solubility in water and surface activity of a 1: 1 Tween 80-protein complex are determined. At the concentrations above the break point on surface tension isotherms (conditionally corresponding to critical association concentration), the particles are formed with radii varying from 16 to 350 nm. At a molar nonionic surfactant/protein ratio in the range of 6–10, the additional binding of Tween 80 molecules by the particles of the new phase due to hydrophobic interactions is observed.
The development of systems for targeted delivery of anti-tuberculosis drugs is a challenge of modern biotechnology. Currently, these drugs are encapsulated in a variety of carriers such as liposomes, polymers, emulsions and so on. Despite successful in vitro testing of these systems, virtually no success was achieved in vivo, because of low accessibility of the foci of infection located in alveolar macrophage cells. A promising strategy for increasing the efficiency of therapeutic action of anti-tuberculosis drugs is to encapsulate the agents into mannosylated carriers targeting the mannose receptors of alveolar macrophages. The review addresses the methods for modification of drug substance carriers, such as liposomes and biodegradable polymers, with mannose residues. The use of mannosylated carriers to deliver anti-tuberculosis agents increases the drug circulation time in the blood stream and increases the drug concentration in alveolar macrophage cells. The bibliography includes 113 references.