DETC-based bacterial cellulose bio-curatives for topical treatment of cutaneous leishmaniasis.

Fabiana S Celes,Camila I De Oliveira,Valeria M Borges,Eliane Trovatti,Hernane S Barud,Johan Van Weyenbergh,Sidney J L Ribeiro,Ricardo Khouri

doi:10.1038/srep38330

Abstract

The treatment of leishmaniasis still relies on drugs with potentially serious adverse effects. Herein, we tested a topical formulation of bacterial cellulose (BC) membranes containing Diethyldithiocarbamate (DETC), a superoxide dismutase 1 inhibitor. Leishmania-infected macrophages exposed to BC-DETC resulted in parasite killing, without pronounced toxic effects to host cells. This outcome was associated with lower SOD1 activity and higher production of superoxide and cytokine mediators. Topical application of BC-DETC significantly decreased lesion size, parasite load and the inflammatory response at the infection site, as well as the production of both IFN-γ and TNF. Combination of topical BC-DETC plus intraperitoneal Sbv also significantly reduced disease development and parasite load. The leishmanicidal effect of BC-DETC was extended to human macrophages infected with L. braziliensis, highlighting the feasibility of BC-DETC as a topical formulation for chemotherapy of cutaneous leishmaniasis caused by L. braziliensis.

Highlights

In the present work, we explored a topical formulation for Cutaneous Leishmaniasis (CL) treatment consisting of bacterial cellulose (BC) membranes loaded with DETC
We show that dried BC membranes loaded with DETC (BC-DETC) significantly reduced L. braziliensis-infection rate in vitro and lesion development in vivo
We previously demonstrated that intraperitoneal injection of DETC is a therapeutic alternative for CL chemotherapy[8,11]

Summary

Introduction

We explored a topical formulation for CL treatment consisting of bacterial cellulose (BC) membranes loaded with DETC. BC is biocompatible, permeable to gas and liquids, it improves wound and burn healing and is managed by the patient Never dried BC’s nanometric dimension and liquid absorption/release capability enable its use as a support for drug release in topical systems[16,17], mainly because of its membranous form. We show that dried BC membranes loaded with DETC (BC-DETC) significantly reduced L. braziliensis-infection rate in vitro and lesion development in vivo. Combination of topical BC-DETC with intraperitoneal Sbv was even more effective against CL development, indicating the feasibility of such approach

Methods

Results

Conclusion