Synthesis, Characterization and Release Studies of Ethylene Diamine Tetraacetic Acid (EDTA)-Antimicrobial Drug Conjugates for Colon Release

Abstract

Background: The colon targeted drug delivery system is mainly useful for the topical treatment of colon diseases such as ulcerative colitis, Crohn’s disease OR colorectal cancers where we attain high local concentration and minimum side effects. In the present study we have synthesized some colon targeted Ethylene diamine tetra acetic acid (EDTA)-antimicrobial drug conjugates. Objectives: The goal of synthesizing EDTA-antimicrobial drug conjugates are that they reach intact in the colon and not be absorbed in the upper GIT, this is because of high molecular weight (>500) of the conjugates (Lipinski’s rule of 5). Materials and Methods: A series of EDTA-antimicrobial drug conjugates (E1-E5) were synthesized by stirring tetra sodium EDTA with antimicrobial drugs viz. Metronidazole (MTZ), Ornidazole (OZ), Ciprofloxacin (CF), Norfloxacin (NF) and Sulfamethoxazole (SM) in presence of EDAC ((1-ethyl-3(3-dimethylaminopropyl) carbodiimide). All the synthesized conjugates were characterized by FTIR, NMR (1H and 13C), Mass spectrometry and elemental analysis to identify structural components. The synthesized conjugates were screened for antimicrobial (antibacterial) and colon release studies. Results and Discussion: On the basis of chemical and spectral analysis EDTA-antimicrobial drug conjugates were synthesized and synthesized conjugates showed good antimicrobial (antibacterial) activity against tested stains. In-vitro release studies of the synthesized conjugates of the series have shown good release results which indicates that synthesized conjugates release the parent drug (antimicrobial drugs) to the colon. Conclusion: Synthesized conjugates improve drug delivery to the intestinal region. Release studies result suggest that the drugs begin to release from the conjugates in the distal intestinal region and appreciable release in the colon has been observed.