Two-step immobilization of metronidazole prodrug on TEMPO cellulose nanofibrils through thiol-yne click chemistry for in situ controlled release

Carbohydr Polym. 2021 Jun 15:262:117952. doi: 10.1016/j.carbpol.2021.117952. Epub 2021 Mar 20.

Abstract

Nowadays, drug encapsulation and drug release from cellulose nanofibrils systems are intense research topics, and commercial grades of cellulose nanomaterials are currently available. In this work we present an ester-containing prodrug of metronidazole that is covalently bound to cellulose nanofibrils in aqueous suspension through a two-step immobilization procedure involving green chemistry principles. The presence of the drug is confirmed by several characterization tools and methods such as Raman spectroscopy, elemental analysis, Dynamic Nuclear Polarization enhanced NMR. This technique allows enhancing the sensitivity of NMR by several orders of magnitude. It has been used to study cellulose nanofibrils substrates and it appears as the ultimate tool to confirm the covalent nature of the binding through thiol-yne click chemistry. Moreover, the ester function of the immobilized prodrug can be cleaved by specific enzyme activity thus allowing controlled drug release.

Keywords: Cellulose nanofibrils; Click chemistry; DNP-NMR; Drug release.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Cellulose / chemistry*
  • Click Chemistry / methods*
  • Cyclic N-Oxides / chemistry
  • Delayed-Action Preparations / chemistry
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Metronidazole / chemistry*
  • Nanofibers / chemistry*
  • Oxidation-Reduction
  • Prodrugs / chemistry*
  • Spectrum Analysis, Raman / methods
  • Sulfhydryl Compounds / chemistry
  • Water / chemistry

Substances

  • Anti-Bacterial Agents
  • Cyclic N-Oxides
  • Delayed-Action Preparations
  • Prodrugs
  • Sulfhydryl Compounds
  • Water
  • Metronidazole
  • Cellulose
  • TEMPO