title: 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 designing delivery systems targeted to the intestinal mucosa. In this study, multiple particle tracking (MPT) was used to study diffusion of 20-500 nm diameter carboxylate- and polyethylene glycol-(PEG-)functionalized polystyrene model carriers through intestinal mucus. The impact of exposure to mucus in buffer versus a partially digested triglyceride mixture was explored. Effective diffusivity of particles in intestinal mucus decreased with an 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- versus 20-fold with increase in the particle size from 100 to 500 nm when dosed to mucus in buffer versus lipid-containing medium. Functionalization with PEG dramatically decreased sensitivity to lipids in a 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.
authors.affiliation: a Department of Chemical Engineering , Northeastern University , Boston , MA , USA and.
authors.forename: Hasan M
authors.initials: HM
authors.lastname: Yildiz
authors.affiliation: b Merck and Co., Inc. , West Point , PA , USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: McKelvey
authors.affiliation: b Merck and Co., Inc. , West Point , PA , USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Marsac
authors.affiliation: a Department of Chemical Engineering , Northeastern University , Boston , MA , USA and.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Carrier
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D007413:Intestinal Mucosa / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry; D013552:Swine; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D008055:Lipids; D011137:Polystyrenes; D014280:Triglycerides; D011092:Polyethylene Glycols
keywords: Diffusion; intestine; lipids; nanoparticles; oral drug delivery; particle transport