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

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. 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.