LYMPHVECs · Development of lipid nanoparticles based on solid matrix for Benznidazole oral delivery targeting to the lymphatic system to treat Chagas disease

According to the WHO there are 8 million persons chronically infected by Chagas disease (CD) resulting in 12.000 reported deaths annually. CD is one of the most significant health problems of Latin America. However, nowadays it has been reported worldwide. Benznidazole (BZ) has been recently approved in US (30/08/2017) as the first option treatment for CD but can only administered for 14 days or less, while it is known that at least 2-3 months of treatment are required for full efficacy. This approval for short-term CD therapy is due to the severe side effects associated with extended use, which severely impacts the applicability of BZ as a universal CD treatment.Importantly, Trypanosoma cruzi (Tc) parasite reservoirs have been localized into the Lymphatic System (LS). Poor compound distribution into the LS could be the reason why extended BZ treatment is required and why reactivation of the parasites in the chronic stage is commonly found.Chagas infected people treated with BZ develop rashes, fever, nausea, headache, allergic dermatitis, digestive intolerance (anorexia), peripheral neuropathy and insomnia. These severe side effects limit its use and foster non-compliance. BZ formulations that reduce compound exposure in system circulation while facilitating distribution into the LS could reduce the efficacious dose (at present 5-7mg/kg/day), reduce side effects, and possibly contribute treatment shortening. This project will develop BZ formulations based on solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) to achieve these three goals.