<p>Colon Targeting of Naringin for Enhanced Cytoprotection Against Indomethacin-Induced Colitis in Rabbits</p>

Abstract

Background: Naringin is a promising anti-inflammatory drug against various disorders including ulcerative colitis. However, its oral bioavailability is low (8%) possibly due to cleavage at the upper gut. Consequently, colon targeting would be necessary for drug protection at the upper gut, enhanced oral bioavailability and potentiated cytoprotection against colitis. Methodology: This study involved the formulation of compression-coated tablets of naringin employing mixtures of pH-sensitive Eudragit L100-55 (EUD-L100-55) and different time-dependent polymers including ethyl cellulose (EC), sodium alginate (ALG) and sodium carboxymethyl cellulose (SCMC). Drug-polymer interaction during release was assessed using Fourier transform-infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Tablets were evaluated in vitro. Surface morphology of the optimized tablets either before or after exposure to the different release media was examined employing scanning electron microscopy (SEM). Cytoprotection potential of the optimized tablets against indomethacin-induced colitis in rabbits was screened and compared to core tablets through a histopathological examination of colon, measurement of serum perinuclear antineutrophil cytoplasmic antibodies (pANCA) and immunohistochemical localization of tumor necrosis factor-alpha (TNF-α). Results: FT-IR and DSC results may indicate drug-polymers interaction during release. Release retardation could be related to polymer swelling that was in the order of SCMC > ALG > EC. SEM examination indicated more porous coats at the buffers relative to the acidic medium. Colon targeting was expected in case of coats of 5% ALG, 5% SCMC and 10% EC (w/w) in combination with EUD-L100-55; thus, they were selected for in vivo evaluation. Effective cytoprotection of selected tablets against indomethacin-induced colitis was indicated by a significant (P<0.05) reduction in mucosal damage, serum levels of pANCA and TNF-α expression compared to untreated colitis and core-pretreated groups. Compared to EC, higher cytoprotection potential of ALG-and SCMC-based tablets was reflected by lower concentration (5% w/w) to provide cytoprotection against indomethacin-induced colitis.

Clinical Demonstrations of Controlled-Release Tablets Constructed by the Combined Usage of Shellac and Hydroxypropyl Methylcellulose

“…Known food-grade delivery systems constructed from xanthan gum mixed with sodium alginate or xanthan gum with chitosan showed faster release profiles than our system [11,12]. Additionally, Naggar et al [15] revealed that a pharmaceutical coating employing methacrylic acid copolymer did not inhibit flowing out at all, and blend coatings with ethyl cellulose, sodium alginate, or sodium carboxymethyl cellulose strongly suppressed drug release in a pH 6.8 solution. These data indicate that our tablet system combined with the shellac coating and the use of HPMC inside possesses an advantage in controlled release compared to known food-grade technologies, though it does not achieve the level of control obtained using pharmaceutical additives.…”

“…However, it has not yet been reported whether the HPMC-containing tablets reached the lower-intestinal sites between the ileum and colon. As indicated by Naggar et al [15], not only HPMC but also a coating technology that protects the tablet from releasing its ingredients in the upper intestine upon exposure to gastric fluid would be necessary for effective gastrointestinal delivery. Shellac is permitted for use in food as a coating material.…”

Synthesis and Characterization of Novel Pyrite/Naringin/Brushite Composite Scaffold for Bone Tissue Engineering

“…-OH [33,37,38] 3439 3442 -OH bonds [40,45] 2919 -CH aliphatic group [37,38] 2929 2929 CH [44] 1644 Carbonyl group [39] 2883 CH [44] 1579 Benzene ring [39] 1738 1733 Carboxylic group [40] 1519 Benzene ring [39] 1628 1635 Carboxylic group [40,45] 1449 Benzene ring [39] 1519 Aromatic OH [63] 1367 -OH phenolic group [42,43] 1421 1416 COOÀ [41] 1296 -OH phenolic group [42,43] 1364 -OH phenolic group [42,43] 1264 Carboxylic group 1266 1267 Carboxylic group [40,45] 1202 -OH phenolic group [42,43] 1073 1074 Alginate ring [41] 1177 -OH phenolic group [42,43] 1030 1030 Alginate ring [41] 1132 -C-O-C [39] 822 822 CH group [41] 1090 Carbonyl group [39] 811 811 CH group [41] 1042 -C-O group [38] 671 671 CH group [41] 900-500 Bending vibration of the ring [43] 556 559 C-O [43] 500-400 500-400 C-C-C [43] immersion in PBS. The spheres release out naringin very fast after soaking.…”