Discovery of low mucus adhesion surfaces

Abstract

Mucus secretion from the body is ubiquitous and finding materials that resist mucus adhesion is a major technological challenge of medical and consumer import. Here, using a high throughput platform (HTP) with photo-induced graft polymerization, we first rapidly synthesized, screened and tested a library of 55 different surfaces from six functional monomer classes to discover porcine intestinal low mucus adhesion surfaces using a 1 hr static mucus adsorption protocol. From this preliminary screen, two chemistries, a zwitterionic ([2-(acryloyloxy)ethyl] trimethylammonium chloride) and a multiple hydroxyl (N-[tris(hydroxymethyl)methyl]acrylamide) surface, exhibited the significantly low mucus adhesion from a Langmuir-type isotherm when exposed to increasing concentrations of mucus for 24 hr. Apolar or hydrophobic interactions were likely the dominant attractive forces during mucus binding since many polar or hydrophilic monomers reduced mucus adhesion. Hansen solubility parameters were used to illustrate the importance of monomer polarity and hydrogen-bonding in reducing mucus adsorption. For a series of PEG monomers with changing molecular weight from 144 g/mol to 1100 g/mol, we observed an excellent linear correlation (R2 = 0.998) between relative amount adsorbed and the distance from a water point in a specialized HSP plot, emphasizing the role of surface-water interactions for PEG modified surfaces.

Enzymatically active biomimetic micropropellers for the penetration of mucin gels

“…1). Thus far, drug carriers and other particles have been treated mostly with substances that modulate mucus-surface interactions, such as polyethylene glycol, various polymers, adsorbed bile salts, lectins, and microbial ligands (7,16,(21)(22)(23)(24). The present study shows that it is possible to significantly enhance the mobility of microparticles in mucin gels by urease immobilization on their surface.…”

“…When placed in pure PGM solution at neutral pH (corresponding to a low viscosity), most of the time, the magnetic propellers appear to rotate when a rotating magnetic field is applied but do not exhibit any forward propulsion, even at very low concentrations of only 0.25% PGM. We postulate that this is due to mucoadhesion ( 1 , 22 , 23 ), that is, the adsorption of mucin to the surface of the particles. One explanation for the low motility is that adsorbed mucin reduces the rotation rate by immobilizing the particles in the polymeric matrix.…”

Probing mucin interaction behavior of magnetic nanoparticles

“…Mucins are the major parts of the heavily glycosylated proteins present in the mucus gel with polypeptide backbones [5–7]. Under normal physiological conditions, mucus composition, viscoelasticity, mucin-to-water ratio, protein, lipid, and ion contents are tightly maintained [8]. This stimulates a protective mechanism of the body that has an excellent ability to immobilize and remove foreign materials such as pathogens, bacteria, and even drugs, by different mucus clearance mechanisms [9–14].…”

Interfacial behavior of lipid nanocapsules spread on model membrane monolayers

“…Recently, the interaction of newly developed LNCs for oral delivery with pig intestinal mucus layer having thickness of several hundred microns were studied by fluorescence resonance energy transfer (FRET) method in order to improve the bioavailability of liposoluble drug Paclitaxel encapsulated in these LNCs [21]. Investigating the processes of adsorption on mucus layer also requires finding a model system where the experimental conditions and physicochemical parameters are under strict control [22,23]. As such, the mucus monolayer at A/W interface appears to be the right candidate.…”