Oral Nano Drug Delivery System Absorption Mechanism
Oral absorption of nanomedicine means that nanomedicine enters the blood circulation through the gastrointestinal tract. Nanomedicine has a very complicated process after entering the body, interacting with the components in the biological system (such as proteins and cells), and has unique distribution, clearance, metabolism and immune response behaviors in the body.
There are three main ways for nanoparticles to be absorbed in the gastrointestinal tract: 1. Cell bypass channel transport; 2. Transcellular uptake by intestinal epithelial cells; 3. Phagocytosis by microfold cells (M cells) in Peyer’s patches in the ileum. Absorption through M cells is the main absorption route of oral nanoparticles. When the nanoparticles enter the gastrointestinal tract, part of the drug is released and enters the blood circulation like the absorption process of free drugs. After the nanoparticles are swallowed, they are transported to the basal cavity of the M cells by cystic transport and released. The nanoparticles are in a free state or in a state of being swallowed by macrophages, with lymphocytes passing through the lymphatic vessels, from the lymphatic circulation into the human blood circulation . The phagocytosis of M cells in the collective lymph nodes opens a channel on the intestinal mucosal epithelial barrier, which constitutes the main physiological pathway for the non-receptor transport of nanoparticles, allowing the nanoparticles to be absorbed into the systemic circulation in a complete structure. Nanoparticles can also promote drug absorption through interaction with the membrane, and the particles themselves do not transport across the membrane. Nanoparticles can be captured by the microvilli of the duodenum and stay for a longer time, prolong the contact time of the drug with the cell wall, and increase the rate and degree of drug absorption.
The main cell models for oral absorption of nanoparticles are Caco-2 and MDCK. Caco-2 cells are derived from human colon adenocarcinoma cells with good homology. The Caco-2 cell monolayer model can distinguish the difference of different absorption pathways in the intestinal cavity, judge the absorption mode, and obtain the kinetic parameters of drug absorption. The shortcomings of Caco-2 cells include lack of intestinal mucus layer, lack of some metabolic enzymes, and barrier properties similar to colonic epithelial cells, but somewhat different from small intestinal epithelial cells. MDCK (Ma-din-Darby canine kidney) cells are the most ideal epithelial cell line in terms of genetics and cellular lipid and protein composition. MDCK cells are polar, the base side is attached to the bottom of the bottle, and the liquid surface layer is formed by microvilli and forms a dome. These cells are very close to the distal convoluted tubules of the kidney. MDCK cells have a shorter culture time than Caco-2 cells, have low transepithelial resistance, and are close to the small intestine. However, the cell monolayer can only be used to predict the passive transport of intestinal epithelial cells, and cannot be used to study or predict the active absorption or efflux of intestinal epithelial cells.
When nanoparticles enter the gastrointestinal tract, they can interact with the membrane to enhance the transcellular pathway of passive penetration of the drug through the cell membrane, increase the transport of the cell bypass channel, and promote drug absorption. Nanoparticles with chitosan and polyvinyl acrylate as polymer materials encapsulate polypeptide drugs (such as insulin). Chitosan reorganizes the tight junction protein structure through the charge-mediated charge of epithelial cells, and strengthens the permeability of bypass transport of polypeptides; Polyvinyl acrylate strengthens the cell bypass transport of polypeptides by reducing the concentration of free extracellular Ca2+, thereby promoting their absorption. Two self-microemulsifying drug delivery systems (SMEDDS) containing the surfactant Labrasol, in which the negatively charged SMEDDS has no significant effect on the monolayer conductivity of Caco-2 cells, while the positively charged SMEDDS has a significant effect on the monolayer conductivity, indicating that the tight junctions of cells are opened.