Sulfhydryl‐Modified Glucomannan: Mucoadhesive Gelling Agent for Controlled Release and Enhanced Oral Bioavailability of Methotrexate

ABSTRACT The development of drug carriers with controlled drug release and improved oral bioavailability is always challenging. Therefore, the purpose of this work is to create sulfhydryl‐modified glucomannan‐containing hydrogels that can cross‐link via disulfide bond formation for the controlled release and enhanced bioavailability of methotrexate (MTX). Newly developed hydrogels were characterized via Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Moreover, thiol contents, swelling behavior, sol–gel fraction, texture analysis and spreadability, rheological properties, safety, and drug release characteristics were investigated. Furthermore, in vivo studies were performed. Hydrogels showed 1769 μmol/g sulfhydryl groups on the glucomannan backbone, and FTIR confirmed no physical interaction, Moreover, there was significantly improved swelling, a 93.6% gel fraction, improved work of adhesion and stiffness, and a 10.3‐fold improved viscosity. The non‐toxic, sulfhydryl‐modified hydrogel exhibited a pH‐dependent drug release. The sulfhydryl‐modified hydrogels showed more than 85% of the drug released at pH 7.4 in comparison to less than 20% of the drug released at pH 1.2. In vivo studies confirmed that in comparison to pure drug suspension, the oral relative bioavailability of MTX‐loaded sulfhydryl‐modified hydrogels was 7.0‐fold higher. These results imply that newly designed hydrogel is a useful tool for controlled release and enhanced oral bioavailability of MTX.