Fenugreek seed mucilage grafted poly methacrylate pH-responsive hydrogel: A promising tool to enhance the oral bioavailability of methotrexate

• Published in: International journal of biological macromolecules Vol. 202; pp. 332 - 344
• Main Authors: Hussain, Hafiz Rashid, Bashir, Sajid, Mahmood, Asif, Sarfraz, Rai Muhammad, Kanwal, Misbah, Ahmad, Nadeem, Shah, Hamid Saeed, Nazir, Imran
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 31.03.2022
• Subjects: acrylamides; albino; Animals; BCS class IV drugs; bioavailability; Biological Availability; Drug Liberation; fenugreek; Fenugreek mucilage; free radicals; HeLa Cells; Humans; Hydrogels; Hydrogen-Ion Concentration; Methacrylates; Methotrexate; Methotrexate - pharmacology; mucilages; Oral bioavailability; pH-responsive hydrogel; pharmacokinetics; polymerization; Rabbits; Rats; Rats, Wistar; Seeds; thermal analysis; toxicity; Trigonella; Trigonella foenum-graecum; Fenugreek mucilage; pH-responsive hydrogel; Oral bioavailability; BCS class IV drugs; Methotrexate
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2022.01.064

This study aimed to develop the Fenugreek seed mucilage-based pH-responsive hydrogel system in order to improve the oral bioavailability of methotrexate (MTX). Fenugreek seed mucilage (FSM) was extracted from Trigonella foenum-graecum seeds. F1-F9 formulations of pH-responsive hydrogels were prepared using various FSM ratios, methacrylic acid (MAA), and methylene bis acrylamide (MBA) via free radical polymerization technique. Swelling behavior and in vitro drug release studies of prepared hydrogels were evaluated. Toxicity studies of prepared hydrogels were performed on normal cells and on Wistar rats (n = 6). Moreover, in vivo pharmacokinetics parameters were studied on albino rabbits. Hydrogels formation was confirmed by FTIR analysis, thermal analysis and SEM studies. The maximum swelling of hydrogel was found to be 384.7% at pH 7.4. MTX-loaded hydrogel showed the controlled release of MTX up to 24 h following Super Case II transport. Prepared hydrogels exhibited no toxicity in normal cells as well as in experimental subjects. MTX loaded hydrogels exhibited less inhibition compared to free MTX on Hela cells. In Vivo studies revealed 7.5-fold improved oral bioavailability of MTX with higher Cmax (928 ng/mL). These results indicate that the pH-responsive hydrogel system based on FSM is a promising tool for the controlled delivery of MTX. [Display omitted] •pH-sensitive hydrogel for the oral delivery of BCS class IV drugs•Pharmacokinetic parameters evaluation in Albino rabbits•Acute oral toxicity study of natural polymeric carrier system