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Pharmacokinetics of Nanomaterials/Nanomedicines
Published in Yasser Shahzad, Syed A.A. Rizvi, Abid Mehmood Yousaf, Talib Hussain, Drug Delivery Using Nanomaterials, 2022
Mulham Alfatama, Zalilawati Mat Rashid
After oral administration, drug should cross various barriers to the blood circulation including the low stomach pH and high acid, intestinal lumen, the layer of mucus on the top of the intestinal epithelium, and lastly the epithelium cells. The stomach is composed of four layers namely from outermost to innermost: the serosa, muscularis externa, submucosa, and mucosa. It is coated by mucus membrane with glands for gastric acid secretion. The intestinal epithelium is the main site for drug absorption assisted by villi to increase the surface area. The physiology of the GIT can hinder the drug absorption and bioavailability as a result of poor mucosal permeability and premature drug degradation prior reaching to sites of absorption (Lin et al. 2017). The presence of P-glycoproteins mediated efflux in the epithelial cell membrane is another barrier against drug absorption. The physiochemical properties of the drug on the other hand may alter the pharmacokinetics attributes. Poor drug solubility impacts absorption negatively as the drug must be soluble at the absorption site. Moreover, inadequate partition coefficient negates drug permeation through lipid membrane. In addition, drug affinity for the first-pass metabolism determines the proportions in the blood and hence the bioavailability (Sharma, Sharma, and Jain 2016).
Recent Developments in Nanoparticulate-Mediated Drug Delivery in Therapeutic Approaches
Published in Jyoti Ranjan Rout, Rout George Kerry, Abinash Dutta, Biotechnological Advances for Microbiology, Molecular Biology, and Nanotechnology, 2022
Janmejaya Bag, Swetapadma Sahu, Monalisa Mishra
Enzymes mediate the delivery of drugs at the specific site of action, which is taken through the oral route. Human alimentary canal possesses various enzymes throughout the digestive tract. Enzymes are catalytic in nature and hence can break the drug before reaching the targeted site (Han and Amidon, 2000; Mura et al., 2013). Therefore, to prevent its degradation from the enzymatic environment before being released to the target site, now the drugs are encapsulated. Cytochrome p-450 3A4 (CYP3A4) enzyme is found in humans (Table 18.1). The P-glycoprotein or multidrug resistance pumps are present in villi of the small intestine, which facilitate absorption. These factors (CYP3A4 and P-glycoprotein) assist in the absorbance of the drugs through villi (Benet et al., 1999; Kamath and Park, 1993; Veronese and Pasut, 2005). These classes of proteins are induced by some substrates and inhibited by specific inhibitors. Cyclosporine and tacrolimus are tested in humans, whereas a cysteine protease inhibitor is tested in the rat model (Aksungur et al., 2011; Pople and Singh, 2010). The inhibitor and inducer of P-glycoproteins and CYP3A4 are inhibited by proteases of cysteine (Paolini et al., 2017). The midazolam, indinavir, and rifabutin are substrate drugs and act upon CYP3A4 enzymes and affect intestinal metabolism (Benet et al., 1999; Sharma et al., 2016; Feleni et al., 2017). Therefore, it is essential to check the enzyme activity and properties before administration of a drug, through the oral or buccal route.
Hazard Characterization and Dose–Response Assessment
Published in Ted W. Simon, Environmental Risk Assessment, 2019
The lining of the small intestine consists of myriad tiny finger-like projections called villi (singular villus). The function of the villi to increase the epithelial surface area available for the absorption of nutrients. Between the villi are invaginations called crypts of Lieberkuhn. The enterocytes, cells of the villi, slough off into the intestinal lumen and are replaced about every three days by new cells migrating upwards from the crypts. The normal state of crypt cells is to proliferate and replace villous enterocytes. Chemical signaling via specific signaling molecules known as cytokines originating from the villous cells and elsewhere regulates the proliferative activity of the crypt cells.54–56
The aqueous extract of Ocimum gratissimum leaves ameliorates acetic acid-induced colitis via improving antioxidant status and hematological parameters in male Wistar rats
Published in Egyptian Journal of Basic and Applied Sciences, 2018
Kehinde P. Olamilosoye, Rufus O. Akomolafe, Olumide S. Akinsomisoye, Modinat A. Adefisayo, Quadri K. Alabi
Weight loss and excessive bleeding of the colonic mucosal wall are one of the major symptoms of colitis. In the present study, animals that were induced with acetic acid (AA) showed a decreased in body weight gain when compared with the control group. In addition, the diarrhea scoring of rats treated with AA was significantly higher when compared with the control group. Compared with the AA group, rats treated with AEOGL at 200 and 400 mg/kg showed an accelerated weight gain toward control group. In this study, AEOGL increase body weight by preventing the fistulae in the gastrointestinal tract e.g. diarrhea. It reduced the inflammation of the large intestine and excessive nutrient losses through diarrhea. Study has shown that administration of AEOGL in rats caused significant histological changes in the intestines, revealing the presence of increased villi and larger goblets cells [30]. The increase in the numbers of villi in the intestine facilitates increase nutrient absorption due to increase in the surface area of the intestine [31]. Furthermore, AEOGL enhances anti-diarrhea effect by inhibiting intestinal motility, partly via muscarinic receptor inhibition [32], thereby facilitating nutrient absorption in the intestine. The significant increase in body weight and decrease in diarrhea scores that were observed in AEOGL groups, may be as a result of AEOGL inhibited the intestinal motility, by increasing number of villi and larger goblets cells of the intestine, which favor rapid absorption of nutrient from the gastro-intestinal tract and subsequently prevented diarrhea.