Abstract
The intestinal epithelium is a major barrier that limits the absorption of oral drugs. The integrity of the epithelial tissue is a very important factor for preventing intestinal diseases. However, destabilization of the epithelium can promote the transportation of nanocarriers and increase the absorption of oral drugs. In our research, three different gold nanoparticles (GNPs) of the same size but with differing negative surface charge were designed and constructed as a model to determine the surface properties crucial for promoting absorptivity and bioavailability of the nanocarriers. The higher the ratio of surface carboxyl groups on GNPs, the higher capacity to induce transepithelial electrical resistance change and cell monolayer tight junction opening with higher permeability. The half carboxyl and half methyl surfaced GNPs displayed unique zonal surface patterns exhibited the greater ability to pass through intestinal epithelial cell layer but had a relatively small influence on tight junction distribution.
Highlights
Oral administration of drugs is often preferred over the parenteral route due to its convenience, safety, and reduced health care costs [1]
Many intestinal diseases are associated with the destruction of the intestinal epithelium, including inflammatory bowel disease [4,5], infectious diarrhea [6], and intestinal tumors [7]
Modification achieving and the balance between optimal intestinal safety and higher permeability of nanoparticles utilized for the delivery of orally administered drugs
Summary
Oral administration of drugs is often preferred over the parenteral route due to its convenience, safety, and reduced health care costs [1]. An intact intestinal epithelium, unstirred water layer, tight junctional complex between cells, and polarized cell membrane have the natural capacity to prevent permeation of exogenous substances (e.g., bacteria, toxins, food antigens, and carcinogens) and protect the human body [2]. Epithelial cell tight junctions are an important component of the intestinal mucosal barrier. Once tight junctions are impaired, permeability increases between intestinal cells, thereby allowing bacteria, endotoxins, and macromolecular substances to enter the circulation system [3]. Many factors, including size [9], surface charge [10,11], hydrophobicity [12], and concentration of nanoparticles, can influence permeation through the epithelial cell monolayer [13]
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