期刊
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 14, 期 5, 页码 543-551出版社
SHENYANG PHARMACEUTICAL UNIV
DOI: 10.1016/j.ajps.2018.09.002
关键词
Mucus barrier; Mucus modulating agents; Rheology; PLGA nanoparticles; Surfactants
资金
- National Natural Science Foundation of China [31870987]
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. (C) 2018 Shenyang Pharmaceutical University. Published by Elsevier B.V.
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