LYMPHVECs · Development of lipid nanoparticles based on solid matrix for Benznidazole oral delivery targeting to the lymphatic system to treat Chagas disease
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-03-01 → 2021-03-31
- EU contribution
- €158,122
- Participants
- 1
- Scheme
- MSCA-IF-EF-SE
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Results in brief
Development of lipid nanoparticles based on solid matrix for Benznidazole oral delivery targeting to the lymphatic system to treat Chagas disease
There are 7 million people chronically infected by Chagas disease resulting in 10,000 deaths reported annually according to the World Health Organization. This disease is one of the most important health problems in Latin America. However, today it has been reported all over the world. So far, there is only one drug approved by the FDA to treat this disease, Benznidazole. Benznidazole has limited efficacy in the chronic phase of this disease. Besides, people infected with Chagas and treated with Benznidazole develop skin rashes, fever, nausea, headache, allergic dermatitis, digestive intolerance (anorexia), peripheral neuropathy, and insomnia. These serious side effects limit its use and encourage non-compliance. In addition, the reservoirs of parasites that cause the disease have been located in the lymphatic system. Therefore, the maldistribution of compounds in this system could be the reason why prolonged treatment with Benznidazole is required and why reactivation of parasites is commonly found in the chronic stage. Thus, developing Benznidazole formulations that reduce the exposure of the compound in the circulatory system while facilitating distribution in the lymphatic system could reduce the effective dose (currently 5-7 mg/kg/day), reduce side effects and possibly help to shorten the treatment. In this project, lipid matrix-based Benznidazole formulations have been investigated and developed to achieve these three goals.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- GLAXOSMITHKLINE INVESTIGACION Y DESARROLLO SL · Tres CantosCoordinatorSpain
Links
Data: CORDIS, © European Union