Development and characterization of miltefosine-loaded polymeric micelles for cancer treatment

Author(s)

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.

• Document type: Journal article
• Source: Materials Science & Engineering C-Materials for Biological Applications; v. 81, p. 327-333, DEC 1 2017.
• Web of Science Citations: 8

Abstract

Miltefosine presents antineoplastic activity but high hemolytic potential. Its use in cancer has been limited to treating cutaneous metastasis of breast cancer. To decrease hemolytic potential, we developed a formulation of miltefosine-loaded polymeric micelles (PM) of the copolymer Pluronic-F127. A central composite design was applied and the analysis of variance showed that the optimum level of hydrodynamic diameter and poly-dispersity index predicted by the model and experimentally confirmed were 29 nm and 0.105, respectively. Thermal analyses confirmed that miltefosine was molecularly dispersed within PM. Pluronic-F127 PM with miltefosine 80 mu M presented a significant reduction of hemolytic effect (80%, p < 0.05) in comparison to free drug. In vitro assays against HeLa carcinoma cells demonstrated similar cytotoxicity to free miltefosine and PM. Our results suggest that, by lowering hemolytic potential, miltefosine-loaded Pluronic-F127 PM a promising alternative to broaden this drug use in cancer therapy, as well as of other alkylphosphocholines. (AU)

• FAPESP's process: 14/01983-0 - Synthesis and nanotechnological development of miltefosine homocholinic analogs
• Grantee: Carlota de Oliveira Rangel Yagui
• Support Opportunities: Regular Research Grants