Modulating intestinal mucus barrier for nanoparticles penetration by surfactants

Abstract

Improving peroral delivery efficiency is always a persistent goal for both small-molecule and macromolecular drug development. However, intestinal mucus barrier which greatly impedes drug-loaded nanoparticles penetration is commonly overlooked. Therefore, in this study, taking fluorescent labeled PLGA (poly (lactic-co-glycolic acid)) nanoparticles as a tool, the influence of anionic and nonionic surfactants on mucus penetration ability of nanoparticles and their mucus barrier regulating ability were studied. The movement of PLGA nanoparticles in mucus was tracked by multiple particles tracking method (MPT).Alteration of mucus properties by addition of surfactants was evaluated by rheology and morphology study. Rat intestinal villus penetration study was used to further evaluate penetration enhancement of nanoparticles. The effective diffusivities of the nanoparticles in surfactants pretreated mucus were increased by 2-3 times and the mucus barrier regulating capacity was also surfactant type dependent. Sodium dodecyl sulfate (SDS) increased the complex viscosity and viscoelastic properties of mucus, but poloxamer presented a decreased trend. Tween 80 maintained the rheological property of the mucus. With the mucus barrier regulated by surfactants, the penetration of nanoparticles in intestinal villus was obviously increased. In summary, the mucus penetration ability of nanoparticles could be enhanced by altering mucus microenvironment with surfactants. Tween 80 which largely retains the original mucus rheology and morphology properties may be a promising candidate for facilitating nanoparticle penetration through the mucus barrier with good safety profile.

Comparing the permeability of human and porcine small intestinal mucus for particle transport studies

“…The authors postulated that Tween micelles might diffuse through the mucus gel, minimally impacting its structure, and interact with hydrophobic regions of the mucus. More recently, Zhang et al 51 showed that the exposure of the porcine small intestinal mucus to Tween 80 reduced the bulk viscosity of the mucus and facilitated nanoparticle penetration through the mucus. The particulate diffusivity was enhanced to a larger extent after the mucus had been treated with sodium dodecyl sulfate, however the authors did not report on how the exposure to this anionic surfactant influenced the surface charge of diffusing nanoparticles.…”

Screening of Surfactants for Improved Delivery of Antimicrobials and Poly-Lactic-co-Glycolic Acid Particles in Wound Tissue

“…These observations can be explained with the fact that surfactants with a higher tendency to form micelles may also better interact with skin components and induce their perturbation, thus promoting PLGA particles penetration in the wound tissue. Comparable results were reported by Zhang et al, who found that PLGA nanoparticle permeation across mucus and the intestinal barrier could be increased by both ionic (SLS) and non-ionic (Tween 80) surfactants with different degrees of penetration enhancement depending on the surfactant physicochemical properties [ 40 ].…”

“…A number of studies have investigated the effects of surfactant on drug and particle penetration across mucus [ 37 , 38 , 39 ]. It was shown that surfactants can modify the mucus by increasing its hydrophilicity and thus particle diffusion across it [ 40 ]. Mucus has a complex composition with electrolytes, lipids, nucleic acids, cell debris, and large glycosylated proteins such as mucin being the main components [ 41 ].…”

Dual Targeting EGFR and STAT3 With Erlotinib and Alantolactone Co-Loaded PLGA Nanoparticles for Pancreatic Cancer Treatment

“…A modified solvent extraction/evaporation technique was used to prepare AE@NPs ( Kou et al, 2017 ; Zhang et al, 2019 ; Zheng et al, 2020 ). In brief, the appropriate amount of PLGA, DSPE-PEG2000, ALA, and ERL was dissolved in dichloromethane (DCM), and then 1% (v/v) PVA solution was added.…”