Colon Targeting of Naringin for Enhanced Cytoprotection Against Indomethacin-Induced Colitis in Rabbits
| Autor: | Mohammed Fawzy Hamed, Eman Ebrahim El Naggar, Thanaa Mohamed Borg, Ahmed R. El-Sheakh, Elham Abdelmonem Mohamed |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pharmacology Chemistry Pharmaceutical Science medicine.disease Cytoprotection Ulcerative colitis Carboxymethyl cellulose Bioavailability 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Ethyl cellulose In vivo 030220 oncology & carcinogenesis Drug Discovery medicine Colitis Naringin medicine.drug |
| Zdroj: | Drug Design, Development and Therapy. 14:677-696 |
| ISSN: | 1177-8881 |
| DOI: | 10.2147/dddt.s218357 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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