Last Updated: 27/08/2024
Dendrimeric prodrugs potentially active in malaria: Use of analytical quality by design (AQBD) for analytical development
Objectives
*Original in Portuguese: Pró-fármacos dendriméricos potencialmente ativos em malária: utilização de analytical quality by design (AQBD) para desenvolvimento analítico
This project aims to develop an analytical testing methodology for these innovative molecules, applying approaches of QbD and (AQbD), which allow, above all, a better evaluation of the performance of experiments. After experiment planning (DoE), which comprises stages of screening and optimization, the tests will be carried out using the proposed design.
Malaria is caused mainly by the etiological agents Plasmodium vivax, Plasmodium falciparum, Plasmodium malariae and Plasmodium ovale, its main vector of infection are mosquitoes of the genus Anopheles and is an endemic disease in different regions of the world that causes hundreds of thousands of deaths annually. O The biggest challenge for treating the disease is the resistance of these agents to drugs antimalarials, such as chloroquine and sulfadoxine – pyrimethamine. The main strategy of treatment consists of the use of artemisinin derivatives associated with two or more drugs, but the evolution of parasite resistance to combined therapies, as well as and the occurrence of adverse events are constant concerns. The Acute Respiratory Distress Syndrome (ARDS) is a serious clinical manifestation that begins quickly develops a lung injury, preventing gas exchange, which can even cause death. To date, there are many difficulties in understanding how the pathogenesis of this clinical manifestation occurs. Some artemisinin derivatives, belong to Class 2 of the Biopharmaceutical Classification System (BCS) presenting little bioavailability when administered orally and little stability in aqueous solutions, with hydrolysis occurring and the formation of possible degradation products. In view of these facts, the present work aims to use tools for Quality by Analytical Design (AQbD) for the analytical development of first-generation PAMAM-derived dendrimeric drugs containing artesunate. These compounds are being synthesized by the research group and under the guidance of Prof. Dr. Jeanine Giarolla Vargas. The aim, after the steps described above, is to obtain more favorable conditions for carrying out analytical development, through an indicative method of Robust and economical stability with regulatory flexibility.
Oct 2023
