4.5 Article

Safety of oral administration of high doses of ivermectin by means of biocompatible polyelectrolytes formulation

Journal

HELIYON
Volume 7, Issue 1, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.heliyon.2020.e05820

Keywords

High dosage; Drug repurposing; Animal model; Histochemistry; Formulation; Immunofluorescence

Funding

  1. Sao Paulo Research Foundation (FAPESP) [15/23948-5, 16/13368-4]
  2. National Council for Scientific and Technological Development (CNPq/Brazil) [303013/2015-0]
  3. CAPES/Brazil
  4. FAPESP [18/20482-3, 17/16722-6]

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The study analyzed the effects of high doses of ivermectin on animal tissues, demonstrating that higher doses did not cause significant damage to intestinal tissues, while also observing random variations in hematological parameters and their apparent recovery process.
The FDA-approved drug ivermectin is applied for treatments of onchocerciasis and lymphatic filariasis. The anti-cancer and anti-viral activities have been demonstrated stressing possibilities for the drug repurposing and therefore new information on high dosage safety is on demand. We analyzed in vivo tissue responses for high doses of ivermectin using Corydoras fish as animal model. We made intestinal histology and hematologic assays after oral administration of ivermectin transported with polyelectrolytes formulation. Histology showed any apparent damage of intestinal tissues at 0.22-170 mg of ivermectin/kg body weight. Immunofluorescence evidenced delocalization of Myosin-Vb at enterocytes only for the higher dose. Hematology parameters showed random variations after 7 days from administration, but a later apparent recover after 14 and 21 days. The study evaluated the potential of high doses of oral administration of ivermectin formulation, which could be an alternative with benefits in high compliance therapies.

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