Thermosensitive hydrogel for <i>in situ</i> -controlled methotrexate delivery
Teresa Darlen Carrillo-Castillo, Antonia Luna‐Velasco, Erasto Armando Zaragoza‐Contreras, Javier S. Castro
Abstract
Abstract Methotrexate (MTX) is widely used for the treatment of various types of cancer; however, it has drawbacks such as low solubility, lack of selectivity, premature degradation, and side effects. To solve these weaknesses, a hydrogel with the ability to contain and release MTX under physiological conditions without burst release was synthesized. The hydrogel was fabricated with a poly( ɛ -caprolactone)- b -poly(ethylene glycol)- b -poly( ɛ -caprolactone) (PCL–PEG–PCL) triblock copolymer, synthesized by ring-opening polymerization. The characterizations by proton nuclear magnetic resonance spectroscopy and Fourier-transform infrared spectrometry confirmed the copolymer assembly, whereas the molecular weight analysis validated the PCL 2000 –PEG 1000 –PCL 2000 structure. The copolymer aqueous solution exhibited sol–gel phase transition at 37°C and injection capacity. The hydrogel supported a load of 1,000 μg MTX·mL −1 , showing a gradual and sustained release profile of the drug for 14 days, with a delivery up to 92% at pH 6.7. The cytotoxicity of the MTX-loaded hydrogel was performed by the methyl thiazole tetrazolium assay, showing a mean inhibitory concentration of 50% of MCF-7 cells (IC 50 ) at 43 µg MTX·mL −1 .