Synthesis and evaluation of amylose-mefenamic acid conjugates as colon-targeting prodrugs

Abstract

Aim: Amide-linked amylose-based prodrugs were developed for colon-targeted release of mefenamic acid. Materials & methods: Activation of prodrug was studied spectrophotometrically, enzyme-linked immunosorbent assay appraised cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibition at different concentrations of the prodrug, the behavior of prodrug under physiological conditions was monitored by scanning electron microscopy. Results: Prodrug was poorly activated in the enzyme-free simulated gastric media and simulated intestinal media (SIM) but preincubation in pancreatin followed by treatment in aminopeptidase containing SIM led to a significant activation of prodrug. Conclusion: Amide-linked amylose-mefenamic acid conjugates showed a slow release in simulated gastric media and a controlled release in SIM with pancreatin playing an important role in drug release.

Summary points

• Amide-linked amylose-mefenamic acid conjugate functions as a prodrug in simulated gastric media (SGM) and simulated intestinal media (SIM).

• A slow release of mefenamic acid from the prodrug was observed in SGM and SIM in the presence of amidase and aminopeptidase.

• Macromolecular size of amylose masks amide linkage of the prodrug from hydrolysis in SGM and SIM.

• Preincubation of the prodrug with pancreatin followed by its treatment in SIM resulted in controlled release of mefenamic acid.

Keywords: :

• ¹HNMR
• amination
• amylose
• controlled release
• mefenamic acid
• pancreatin
• prodrug
• simulated intestinal media
• tosylation
• zeroth order

Author contributions

S Chugh: Synthesis, data acquisition, manuscript preparation. M Sharma: Data analysis, characterization, revisions. H Mudila: Result interpretation, revisions. P Prasher: Conceptualization, designing of experiments, manuscript preparation.

Financial disclosure

The authors duly acknowledge the Research Grant from DST-SERB, India for supporting this work. PP Thanks DST-SERB for TARE fellowship (File No. TAR/2021/000129). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing Dislosure

No writing assistance was utilized in the production of this manuscript.

Acknowledgments

The authors duly acknowledge the Research Grant from DST-SERB, India for supporting this work. P Prasher thanks DST-SERB for TARE fellowship (file No. TAR/2021/000129).

Additional information

Funding

The authors duly acknowledge the Research Grant from DST-SERB, India for supporting this work. PP Thanks DST-SERB for TARE fellowship (File No. TAR/2021/000129). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.