Synthesis and release studies on amylose-based ester prodrugs of fenamic acid NSAIDs

Ther Deliv. 2024;15(10):769-779. doi: 10.1080/20415990.2024.2400041. Epub 2024 Sep 17.

Abstract

Aim: To achieve colon-targeted release of mefenamic acid from its ester-linked amylose prodrugs.Materials & methods: The prodrug was characterized by 1H NMR and IR spectroscopy. Drug activation and release profile was studied in enzyme enriched simulated physiological media via UV-vis spectroscopy and was validated with HPLC analysis. ELISA assay was employed for evaluating the % inhibition of COX-1 and COX-2 inhibition at different concentrations of the prodrug preincubated with ester and/ or amylose hydrolyzing enzymes. SEM studies further validated the performance of the prodrug under simulated physiological conditions.Results: Pancreatin was essential for the prodrug activation in SIM to make the ester bonds in prodrug vulnerable to hydrolysis by esterase. This evidence was confirmed by drug release studies, HPLC analysis, ELISA assay and SEM investigation where the ester conjugated prodrug showed marked stability in physiological media only to get activated in the presence of amylose degrading enzyme.Conclusion: Ester linked amylose-mefenamic acid conjugate showed both enzyme responsive activation and release in SIM.

Keywords: 1H NMR; ELISA; SEM analysis; amylose; controlled release; esterase; intestine; mefenamic acid; pancreatin; prodrug.

Plain language summary

[Box: see text].

MeSH terms

  • Amylose* / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal* / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
  • Cyclooxygenase 1 / chemistry
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Drug Liberation*
  • Drug Stability
  • Esters / chemistry
  • Humans
  • Hydrolysis
  • Mefenamic Acid / chemistry
  • Mefenamic Acid / pharmacology
  • Prodrugs* / chemical synthesis
  • Prodrugs* / chemistry
  • Prodrugs* / pharmacology

Substances

  • Prodrugs
  • Amylose
  • Anti-Inflammatory Agents, Non-Steroidal
  • Mefenamic Acid
  • Esters
  • Cyclooxygenase 1
  • Cyclooxygenase 2