Ibuprofen is a common nonsteroidal anti-inflammatory drug (NSAID) clinically used for its antipyretic and analgesic effects. However, drawbacks of oral administration of Ibuprofen include gastric irritation, gastric bleeding etc. Hence a colon-targeting delivery system must be opted to avoid its side effects on the upper - gastrointestinal tract .β-Cyclodextrin (β-CyD) is a kind of macrocyclic oligosaccharides composed of seven α-1, 4-linked D-glucopyranose subunits intriguing many researchers in developing β-CyD-based conjugates lately. The primary conjugate of ibuprofen with β-CyD synthesised and evaluated by Dhaneshwar et al.was effective in covering up the –COOH groups, thus reducing its ulcerogenic effects. Studies showed that the solubility of the primary conjugate of β-CyD was poor, and the strong intramolecular hydrogen bond between the secondary hydroxyl groups could be a possible reason for it. Polyethylene glycol (PEG) is commonly used to increase the water solubility, chemical stability, and half-life of drugs. In the present study, NSAIDs ibuprofen was chemically conjugated to the PEG-graft-β-CyD with an ester bond and its aqueous solubility was enhanced.
β-Cyclodextrin
The synthesis of the ibuprofen-β-CyD-PEG conjugate was a simple process consisting of two steps. The first step comprised the synthesis of PEG-graft-β-CyD by using the combination of β-CyD and PEG in the presence of dicyclohexylcarbodiimide (DCC), followed by the second step, in which ibuprofen (Ibu) was conjugated to PEG-graft-β-CyD through an ester bond. Pharmacological studies were conducted on Male Kunming mice (25 ± 2.0 g). Ibuprofen-β-CyD-PEG conjugate released only trace amounts of ibuprofen in the contents of the stomach, merely 7.4% ibuprofen was found in the contents of the small intestine, and up to 58.7% in the contents of the colon after 12 h respectively. These results indicated that the polymeric conjugate was site-specifically biodegraded in the rat colonic contents. Evaluation of the anti-inflammatory, analgesic and antipyretic activities of the polymeric conjugate was conducted by the xylene-induced ear swelling technique, the hot plate test, and the brewer's yeast-induced hyperthermia model in mice, respectively.
Hence, by designing conjugates of drugs colon-targeting drug delivery can be achieved, which can integrally survive passage through the stomach and release active moiety by enzymes in the colon. Moreover, the polymeric conjugate demonstrated a long and stable pharmacodynamic efficiency over a 24 h period in mice, including the anti-inflammatory, analgesic, and antipyretic activities. Therefore, the polymeric ibuprofen-cyclodextrin-PEG conjugate may be significant as an orally administered long-acting prodrug of ibuprofen through colon-targeting delivery.
Reference:
Qing Huang, Chun Hua Yan, Sheng Xia Luo, Zhi Xin Li, Tai Bao Wei, Zhi Zhong Wang,"Synthesis, Characteristics, and Pharmaceutical Properties of Ibuprofen-Cyclodextrin-PEG Conjugate", Journal of Chemistry, vol. 2022, Article ID 3388712, 7 pages, 2022. https://doi.org/10.1155/2022/3388712
by Gauri pillai
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