Size selectivity of intestinal mucus to diffusing particulates is dependent on surface chemistry and exposure to lipids

Abstract

Intestinal mucus provides a significant barrier to transport of orally delivered drug carriers, as well as other particulates (e.g., food, microbes). The relative significance of particle size, surface chemistry, and dosing medium to mucus barrier properties is not well characterized but important in design of delivery systems targeted to the intestinal mucosa. In this study, multiple particle tracking (MPT) was used to study diffusion of 20- to 500-nm diameter carboxylate- and polyethylene glycol- (PEG-) functionalized polystyrene model carriers through intestinal mucus. The impact of exposure to mucus in buffer vs. a partially digested triglyceride mixture was explored. Effective diffusivity of particles in intestinal mucus decreased with increasing particle size less than and more than theoretically (Stokes-Einstein) expected in a homogenous medium when dosed in buffer and model fed state intestinal contents, respectively. For example, effective diffusivity decreased 2.9- vs. 20-fold with increase in particle size from 100 to 500 nm when dosed to mucus in buffer vs. lipid-containing medium. Functionalization with PEG dramatically decreased sensitivity to lipids in dosing medium. The results indicate that reduction of particle size may increase particle transport through intestinal mucus barriers, but these effects are strongly dependent on intestinal contents and particle surface chemistry.

Self‐Targeting, Immune Transparent Plasma Protein Coated Nanocomplex for Noninvasive Photothermal Anticancer Therapy

“…Thus, SPARC protein was expected to effectively boost the accumulation of such albumin‐like nanocarrier system, here the PPy‐PEI‐P NCs, to selective target cancer cells through SPARC‐mediated cellular albumin uptake and for the subsequent specific photothermal treatment. The intestinal ECM and associated mucus layer produced by the intestinal cells is a porous structure, and those pores allow passage of particles with sizes below 500 nm even though it is negatively charged as noted in literature . In this study, the SPARC existing on the ECM produced by the intestinal cancer cell fortunately provides the niche as a target site to bind the developed carrier system for subsequent endocytosis for selective thermal treatment.…”

Unravelling the mechanisms that determine the uptake and metabolism of magnetic single and multicore nanoparticles in aXenopus laevismodel

“…It has been hypothesized that this occurs by reduction of particle-mucus interactions. 40 There is also evidence that PEG-coating can decrease macrophage or HeLa uptake of iron particles where the polymer increases uptake hindrance compared with uncoated NPs. 41 Another possible explanation for the morphological alterations observed at higher doses of nanoparticles could be the presence of polyol used during the MC synthesis.…”

Mucus models to evaluate the diffusion of drugs and particles

“…FRAP analysis demonstrated that diffusion of antibodies (IgG, IgA, and IgM) was slowed 3- to 5- fold due to low-affinity interactions within a mucus gel relative to diffusion in distilled water[48]. FRAP analysis also showed that model bile salt micelle diffusion was slowed 3-fold in mucus relative to buffer, while diffusion of molecular species that comprise bile micelles was not affected[49], indicating that bile micelles likely stay intact within the mucus barrier.…”