Synthesis and nanotechnological development of miltefosine homocholinic analogs

• Grant number: 14/01983-0
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2014
• End date: June 30, 2016
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Carlota de Oliveira Rangel Yagui
• Grantee: Carlota de Oliveira Rangel Yagui
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Daniela Sanchez Basseres ; Leandro Ramos Souza Barbosa

Abstract

Chemotherapeutic treatment of cancer with drugs such as alkylating agents, antimetabolites and antimitotics is associated to severe toxicity, damaging health cells and compromising many organs. Alkylphosphocholines (APCs), on the other hand, are a promising class of antitumor agents since they act in the cell membrane and in protein kinases inhibition. APCs prototype corresponds to Miltefosine and is clinically approved for cutaneous metastasis of breast cancer. However, this drug presents gastrointestinal toxicity and hemolytic effect. Recently, a novel Miltefosine analog, Erucilphosphocholine, was synthesized and represented an important step forward since this drug can be employed intravenously. Interestingly, its homocholine analog Erufosine presents hemolytic activity even lower and has been considered a promising structure. In this project novel homocholinc analogs of miltefosine will be sinthesized and have their hemolytic and antiproliferative effects investigated. Additionally, we will investigate alkylphosphocholines encapsulation in polymeric micelles aiming at improving the pharmacokinetic and pharmacodynamic properties, as well as reducing hemolytic and gastrointestinal toxicities. To obtain the micelles, poly(ethylene oxide)-poly(propylene oxide) copolymers, Pluronics®, of different molecular weights will be employed. Initial studies will be conducted with pure comercial Miltefosine and, following, the analogs obtained might be employed. Stability of micelles over dilution will also be investigated and, finally, in vitro releasing studies will be performed. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VALENZUELA-OSES, JOHANNA K.; GARCIA, MONICA C.; FEITOSA, VALKER A.; PACHIONI-VASCONCELOS, JULIANA A.; GOMES-FILHO, SANDRO M.; LOURENCO, FELIPE R.; CERIZE, NATALIA N. P.; BASSERES, DANIELA S.; RANGEL-YAGUI, CARLOTA O.. Development and characterization of miltefosine-loaded polymeric micelles for cancer treatment. Materials Science & Engineering C-Materials for Biological Applications, v. 81, p. 327-333, DEC 1 2017. (14/01983-0)

FEITOSA, VALKER ARAUJO; DE ALMEIDA, VINICIUS CORDEIRO; MALHEIROS, BARBARA; DE CASTRO, RAPHAEL DIAS; SOUZA BARBOSA, LEANDRO RAMOS; PEREIRA CERIZE, NATALIA NETO; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Polymeric micelles of pluronic F127 reduce hemolytic potential of amphiphilic drugs. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 180, p. 177-185, AUG 1 2019. (15/15822-1, 14/01983-0)

PACHIONI-VASCONCELOS, JULIANA DE ALMEIDA; LOPES, ANDRE MORENI; APOLINARIO, ALEXSANDRA CONCEICAO; VALENZUELA-OSES, JOHANNA KARINA; RIBEIRO COSTA, JULIANA SOUZA; NASCIMENTO, LAURA DE OLIVEIRA; PESSOA, JR., ADALBERTO; SOUZA BARBOSA, LEANDRO RAMOS; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Nanostructures for protein drug delivery. BIOMATERIALS SCIENCE, v. 4, n. 2, p. 205-218, 2016. (14/01983-0, 13/16588-7, 13/08617-7, 14/10456-4)