Author(s): Cerqueira, Patrícia ; Noro, Jennifer Martins ; Moura, Sofia ; Guimarães, Diana ; Silva, Carla ; Cavaco-Paulo, Artur ; Loureiro, Ana Isabel Sá
Date: 2019
Persistent ID: https://hdl.handle.net/1822/60532
Origin: RepositóriUM - Universidade do Minho
Subject(s): PTS micelles; Methotrexate di-ethylated; Prodrug; Auxiliary solvent method; Sonication method; Cancer therapy
Polyoxyethanyl--tocopheryl sebacate (PTS) is an amphiphilic compound with self-emulsifying properties known to form micelles. In this work, we report the production of PTS micelles for the encapsulation and delivery of a hydrophobic derivative of methotrexate, MTX di-ethylated (MTX-OEt). We optimized the micelles production by testing two different techniques: auxiliary solvent and sonication. Small and homogeneous micelles ( 40 nm) were obtained through the auxiliary solvent method performed at 30 °C and using 15 mg/mL of PTS. The produced micelles with the most promising physicochemical properties did not induce cytotoxicity when tested in normal human cells (BJ5ta cells), being considered for the encapsulation of MTX-OEt. This prodrug was achieved by Fisher esterification using ethanol, being isolated in good yield (= 68 %). MTX-OEt was efficiently encapsulated onto the produced micelles which preserved their physicochemical properties. The PTS micelles loaded with MTX-OEt, free MTX-OEt and free unmodified MTX revealed similar biological effect against cancer cells (Caco-2 cells). These results demonstrated that the biological activity of MTX is not altered after modification. The developed PTS micelles revealed a promising intracellular delivery performance with potentiality for cancer therapy.
