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Comparative hydrodynamic and nanoscale imaging study on the interactions of teicoplanin-A2 and bovine submaxillary
Taewoo Chun1, Jacob Pattem1,2, Richard B Gillis3
1National Centre for Macromolecular Hydrodynamics, University of Nottingham, Sutton Bonington, LE12 5RD, UK.
Abstract:
Glycopeptide antibiotics are regularly used in ophthalmology to treat infections of Gram-positive bacteria. Aggregative interactions of antibiotics with mucins however can lead to long exposure and increases the risk of resistant species. This study focuses on the evaluation of potential interactions of the last line of defence glycopeptide antibiotic teicoplanin with an ocular mucin model using precision matrix free hydrodynamic and microscopic techniques: sedimentation velocity in the analytical ultracentrifuge (SV-AUC), dynamic light scattering (DLS) and atomic force microscopy (AFM). For the mixtures of teicoplanin at higher doses (1.25 mg/mL and 12.5 mg/mL), it was shown to interact and aggregate with bovine submaxillary mucin (BSM) in the distributions of both sedimentation coefficients by SV-AUC and hydrodynamic radii by DLS. The presence of aggregates was confirmed by AFM for higher concentrations. We suggest that teicoplanin eye drop formulations should be delivered at concentrations of < 1.25 mg/mL to avoid potentially harmful aggregations.
Insights
Teicoplanin, an antibiotic for eye infections, can aggregate with mucins at higher doses. To prevent harmful aggregations and potential resistance, teicoplanin eye drops should be formulated below 1.25 mg/mL.
Area of Science:
- Ophthalmology
- Microbiology
- Biochemistry
Background:
- Glycopeptide antibiotics are crucial for treating Gram-positive bacterial eye infections.
- Antibiotic-mucin interactions can prolong drug exposure, increasing the risk of antibiotic resistance.
- Understanding these interactions is vital for optimizing ophthalmic formulations.
Purpose of the Study:
- To investigate the interaction between the glycopeptide antibiotic teicoplanin and an ocular mucin model.
- To evaluate the impact of teicoplanin concentration on mucin aggregation.
- To determine safe concentration limits for teicoplanin in ophthalmic formulations.
Main Methods:
- Sedimentation velocity in analytical ultracentrifugation (SV-AUC) to analyze aggregation.
- Dynamic light scattering (DLS) to measure hydrodynamic radii.
- Atomic force microscopy (AFM) to visualize aggregate formation.
Main Results:
- Teicoplanin interacted with bovine submaxillary mucin (BSM) at concentrations of 1.25 mg/mL and 12.5 mg/mL.
- SV-AUC and DLS showed changes in sedimentation coefficients and hydrodynamic radii, indicating aggregation.
- AFM confirmed the presence of teicoplanin-mucin aggregates at higher concentrations.
Conclusions:
- Teicoplanin can form aggregates with ocular mucins at concentrations ≥1.25 mg/mL.
- These aggregations may lead to prolonged exposure and increased risk of resistance.
- Teicoplanin ophthalmic formulations should ideally be used at concentrations <1.25 mg/mL to mitigate aggregation risks.
