Thermosensitive hydrogel for in situ-controlled methotrexate delivery
Resumen
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 conditionswithout burst release was synthesized.
The hydrogel was fabricated with a poly(ɛ-caprolactone)-bpoly(
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
PCL2000–PEG1000–PCL2000 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 (IC50) at 43 μg MTX·mL−1.