Obtaining a new formulation of nanoparticles, LDE-melphalan: Synthesis of a lipophilic derivative of the chemotherapeutic agent, preparation of lipid nanoparticles and incorporation, stability, cytotoxicity and in vivo pharmacological tests.

• Grant number: 24/06249-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date until: June 01, 2024
• End date until: May 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Raul Cavalcante Maranhao
• Grantee: Jaqueline Moraes Bazioli
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 20/16215-0 - Lipid core nanoparticles (LDE) as vehicles of chemotherapeutic agents: a new standard for the medical therapeutics, AP.TEM

Abstract

The production of nanoparticles, named by LDE, in our laboratory is already well standardized for some chemotherapeutics, such as paclitaxel, docetaxel, daunorubicin, etoposide and methotrexate. The modification of the chemical structure of the drug by esterification reactions is necessary to increase lipophilicity and ensure the incorporation of these drugs into the nanoparticles, thus obtaining stable preparations. In this way, LDE works as a drug-targeting system, preferentially reaching the target cells or tissues, with a drastic reduction in the side effects that occur with the use of chemotherapy drugs in their conventional presentation. Recently, we showed that the use of LDE-etoposide for bone marrow transplantation (BMT) in acute myeloid leukemia had excellent results, reducing toxicity, decreasing acute rejection, and increasing 2-year survival by 70%. The melphalan is used in autologous BMT in patients with multiple myeloma and also in solid tumors such as ovarian carcinoma and neuroblastoma. This study hypothesizes that the use of melphalan associated with LDE can bring great benefit in the BMT of patients with multiple myeloma, like as our results with the use of LDE-etoposide in BMT of leukemias, minimizing the suffering of patients and providing great advances in myeloma therapy. The project aims to obtain the lipophilic derivative of melphalan to facilitate the incorporation and stability of the drug in the LDE; the development of the technique for incorporating this molecule into the LDE; physicochemical characterization of the preparation; cytotoxicity assays; and pharmacokinetic, and pharmacodynamic, and toxicity tests in mice.