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Cyclodextrin inclusion complexes enhance the solubility and anti-virulence activity of metronidazole against

Rehab Mahmoud Abd El-Baky1,2, Zeinab Fathalla3, Hala Rady Ahmed1

  • 1Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia, Egypt.

Plos One
|July 27, 2026
PubMed

Insights

Cyclodextrin complexation enhances metronidazole

Area of Science:

  • Pharmaceutical Sciences
  • Microbiology
  • Drug Delivery

Background:

  • Proteus mirabilis is a significant cause of catheter-associated urinary tract infections and kidney stones.
  • Multidrug resistance in P. mirabilis necessitates novel therapeutic strategies.
  • Improving drug solubility and bioactivity is a key pharmaceutical approach.

Purpose of the Study:

  • To prepare and characterize inclusion complexes of metronidazole with alpha-cyclodextrin (α-CD), beta-cyclodextrin (β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD).
  • To evaluate the impact of cyclodextrin complexation on metronidazole's in vitro release, antimicrobial activity, and anti-virulence properties against P. mirabilis.

Main Methods:

  • Preparation of metronidazole-cyclodextrin inclusion complexes via physical mixing and kneading.
  • Characterization using differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR).
  • In vitro assessment of drug release, minimum inhibitory concentration (MIC), and effects on bacterial motility, urease activity, and biofilm formation at sub-MIC levels.

Main Results:

  • β-CD and HP-β-CD complexes exhibited improved in vitro release profiles compared to metronidazole alone.
  • HP-β-CD complexes demonstrated a four-fold reduction in MIC against P. mirabilis.
  • Sub-MIC concentrations of β-CD and HP-β-CD formulations significantly suppressed bacterial motility, urease-associated phenotypes, and biofilm formation.

Conclusions:

  • Cyclodextrin complexation enhances the physicochemical properties and anti-virulence potential of metronidazole against P. mirabilis.
  • HP-β-CD and β-CD formulations show promise for adjunctive therapy in P. mirabilis infections.
  • Further in vivo studies are warranted to confirm the clinical relevance of these findings.

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