Oral drug delivery systems using chemical conjugates or physical complexes

Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration

“…Thanks to their distinctive core-shell structure, polymeric micelles possess high loading capacity of poorly water-soluble drugs within the hydrophobic inner core; whereas the hydrophilic corona confers aqueous solubility and steric stability, which also protects the encapsulated drug from inactivation in gastrointestinal components (Croy & Kwon, 2006;Liang et al, 2015). Importantly, due to the small size of micelles, previous reports described that the drugloaded nanoparticles could be absorbed in intact form by enterocytes or M cells via endocytic pathway after oral administration (Mathot et al, 2007;Li et al, 2010;Al-Hilal et al, 2013). Thereafter, the micellar delivery system is possible to improve pharmacokinetic and biodistribution profiles, such as longer blood circulation and higher targeting activity by passive or active mechanisms (Lian et al, 2013;Rezazadeh et al, 2015).…”

Poly(amido amine) dendrimers in oral delivery

“…The enzymatic activity of GI tract often leads to intracellular hydrolysis and degradation of macromolecules after their absorption by endocytosis through enterocytes. 4 There are 2 major mechanisms of drug transport across GI epithelium: a) Paracellular, b) Transcellular. Paracellular transport involves passive diffusion of substances through the intercellular spaces in between epithelial cells and is under the control of tight junctions.…”

“…The tunica submucosa is the layer that is surrounded by vasculature and vessels of lymphatic systems. 4,5 The intestinal epithelial cells (IECs) consist of absorptive enterocytes and secretory IECs including goblet cells, enteroendocrine cells, and Paneth cells. The IECs are organized in the crypts and villi of the intestinal epithelium.…”

Gut Microbiota-Mediated Drug-Antibiotic Interactions

“…administered drugs are metabolized primarily to hydrophilic metabolites via sulfation, glucuronidation, and oxidation in tissues such as the liver. They are then partially excreted in the intestine via the bile; however, the gut microbiota then converts the excreted metabolites into deconjugated compounds, which are reabsorbed into the blood (Abe et al, 1990;Al-Hilal et al, 2013). Drugs such as acetaminophen, indomethacin, irinotecan, morphine, and digoxin are often conjugated as glucuronides and sulfates and are excreted in the bile (Peppercorn and Goldman, 1976;Simon and Gorbach, 1984;Orme and Back, 1990).…”

“…Orally administered drugs are absorbed through the epithelial membrane into the blood. The efficiency of this process is dependent on the solubility, stability, and permeability of the drug, as well its metabolism by enzymes secreted by the body and gut microbiota (Davis, 2005;Lennernäs and Abrahamsson, 2005;Al-Hilal et al, 2013). Numerous studies have focused on understanding how drug bioavailability resulting from the solubility, permeability, and stability in the stomach and duodenum affects drug availability; however, the metabolism of drugs by the gut microbiota has been studied in less detail.…”