Evaluation of hematin anhydride as a nanocarrier: mechanisms of its cellular interaction and use for drug delivery against protozoan of Leishmania genus

• Grant number: 19/14525-4
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2019
• End date: November 30, 2022
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Preventive Veterinary Medicine
• Principal Investigator: Marina Tiemi Shio
• Grantee: Marina Tiemi Shio
• Host Institution: Universidade de Santo Amaro (UNISA). São Paulo , SP, Brazil
• Associated researchers: Arlei Marcili ; Carolina Nunes França

Abstract

Research on new drug delivery systems, especially for the intracellular environment, has increased, aiming to decrease the dose of the drug, to improve its activity and to allow the reuse of previously unused antibiotics by the development of resistance. The present project aims to use hematin anhydride as a drug carrier. During the synthesis of hematin anhydride, it is possible to include substances/drugs that can enter into the spaces formed by the domains of nanocrystals. In addition, synthesized hemozoin has amphiphilic properties that allow the incorporation of several substances in the already formed crystal. This nanocrystal when injected intraperitoneally or during the course of natural infection accumulates within organs such as the bone marrow, spleen and liver. Coincidentally, these organs are the same as those affected by visceral leishmaniasis. In addition, macrophages are the host cells of parasites of Leishmania genus and do phagocytosis of hematin anhydride. Hemozoin induces the production of many microbicidal and pro-inflammatory molecules such as IL-1b, in a manner dependent on an intracellular protein complex - the inflammasome. However, hematin anhydride-activated surface receptors was less studied, as well as the impact of drug adsorption on crystal on its recognition and activation of intracellular cascades. In this line of thought, the project intends to evaluate the property of the hematin anhydride for delivery of drugs within macrophages infected with Leishmania infantum chagasi and for treatment of experimental model of visceral leishmaniasis. In addition, it will evaluate the effect on response and phenotype of macrophages. Results obtained from the present project would improve the treatment of canine leishmaniasis and indirectly reducing the transmission source of the disease (AU)