Preclinical Safety Assessment of Chemically Cross-Linked Modified Mandua Starch: Acute and Sub-Acute Oral Toxicity Studies in Swiss Albino Mice.

Abstract

In the present era, 28 days of repeated-dose-toxicity study following the Organization for Economic Cooperation and Development (OECD) guidelines 407 is compulsory for every drug to go through phase 1 clinical trials. The increasing demand for high-resistant starch containing nutraceuticals and the applicability of modified starch in development of targeted drug delivery inspired us to investigate the toxic profile of mandua starch chemically cross-linked by epichlorohydrin and compare it with alkali-isolated starch in healthy adult Swiss albino mice, which can be the first step for exploring the use of epichlorohydrin-cross-linked mandua starch (ECC-MS) as a pharmaceutical excipient. Histopathological examinations of the kidney and liver did not expose noteworthy abnormalities in the treated mice. There were no clinical and mortality symptoms of toxicity observed during the repeated-dose-toxicity study. The oral consumption of ECC-MS did not pose any harm as it was neither lethal nor had any harmful hematological, biochemical, psychological, anatomical, and behavioral effects. The use of ECC-MS and alkali-isolated mandua starch (AMS) was found safe at a dose of 2000 mg/kg body weight in the acute toxicity study and at doses of 2000, 1500, and 1000 mg/kg body weight in the sub-acute toxicity study as no detrimental effects were observed after oral administration in mice for 14 and 28 days, respectively.