Conjugates of Degraded and Oxidized Hydroxyethyl Starch
and Sulfonylureas: Synthesis, Characterization, and in Vivo Antidiabetic
Activity
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Abstract
Orally administered drugs usually
face the problem of low water
solubility, low permeability, and less retention in bloodstream leading
to unsatisfactory pharmacokinetic profile of drugs. Polymer conjugation
has attracted increasing interest in the pharmaceutical industry for
delivering such low molecular weight (<i>M</i><sub>w</sub>) drugs as well as some complex compounds. In the present work, degraded
and oxidized hydroxyethyl starch (HES), a highly biocompatible semisynthetic
biopolymer, was used as a drug carrier to overcome the solubility
and permeability problems. The HES was coupled with synthesized <i>N</i>-arylsulfonylbenzimidazolones, a class of sulfonylurea
derivatives, by creating an amide linkage between the two species.
The coupled products were characterized using GPC, FT-IR, <sup>1</sup>H NMR, and <sup>13</sup>C NMR spectroscopy. The experiments established
the viability of covalent coupling between the biopolymer and <i>N</i>-arylsulfonylbenzimidazolones. The coupled products were
screened for their in vivo antidiabetic potential on male albino rats.
The coupling of sulfonylurea derivatives with HES resulted in a marked
increase of the hypoglycemic activity of all the compounds. 2,3-Dihydro-3-(4-nitrobenzensulfonyl)-2-oxo-1<i>H</i>-benzimidazole coupled to HES<sub>10100</sub> was found
most potent with a 67% reduction in blood glucose level of the rats
as compared to 41% reduction produced by tolbutamide and 38% by metformin