Taewoo Chun's research while affiliated with University of Nottingham and other places

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.

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 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 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 and to reduce the risk of antimicrobial resistance

The natural glycopeptide antibiotic teicoplanin is used for the treatment of serious Gram-positive related bacterial infections and can be administered intravenously, intramuscularly, topically (ocular infections), or orally. It has also been considered for targeting viral infection by SARS-CoV-2. The hydrodynamic properties of teicoplanin A2 (M1 = 1880 g/mol) were examined in phosphate chloride buffer (pH 6.8, I = 0.10 M) using sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge together with capillary (rolling ball) viscometry. In the concentration range, 0–10 mg/mL teicoplanin A2 was found to self-associate plateauing > 1 mg/mL to give a molar mass of (35,400 ± 1000) g/mol corresponding to ~ (19 ± 1) mers, with a sedimentation coefficient s20, w = ~ 4.65 S. The intrinsic viscosity [η\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta$$\end{document}] was found to be (3.2 ± 0.1) mL/g: both this, the value for s20,w and the hydrodynamic radius from dynamic light scattering are consistent with a globular macromolecular assembly, with a swelling ratio through dynamic hydration processes of ~ 2.

The semi-synthetic glycan antibiotic teicoplanin is used for the treatment of serious Gram-positive related bacterial infections and can be administered intravenously, intramuscularly, topically (ocular infections), or orally. It has also been considered for targeting viral infection by SARS-CoV-2. The hydrodynamic properties of teicoplanin A2 (monomer molar mass ~ 1880 g/mol) were examined in phosphate chloride buffer (pH 6.8, I = 0.10 M) using sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge together with capillary (rolling ball) viscometry. In the concentration range, 0-10 mg/mL teicoplanin A2 was found to self-associate plateauing > 1 mg/mL to give a molar mass of (35400 ± 1000) g/mol corresponding to ~ (19 ± 1) mers, with a sedimentation coefficient s20,w = ~ 4.65 S. The intrinsic viscosity [h] was found to be (3.2 ± 0.1) mL/g: both this, the value for s20,w and the hydrodynamic radius from dynamic light scattering is consistent with a globular macromolecular assembly, with a swelling ratio through dynamic hydration processes of ~2.

Hyaluronic acid (HA) has been commonly used in eyedrop formulations due to its viscous lubricating properties even at low concentration, acting as a supplement for ocular mucin (principally MUC5AC) which diminishes with aging in a condition known as Keratoconjunctivitis sicca or "dry eye". A difficulty has been its short residence time on ocular surfaces due to ocular clearance mechanisms which remove the polysaccharide almost immediately. To prolong its retention time, tamarind seed gum polysaccharide (TSP) is mixed as a helper biopolymer with HA. Here we look at the hydrodynamic characteristics of HA and TSP (weight average molar mass Mw and viscosity ) and then explore the compatibility of these polymers, including the possibility of potentially harmful aggregation effects. The research is based on a novel combination of three methods: sedimentation velocity in the analytical ultracentrifuge (SV-AUC), size-exclusion chromatography coupled to multiangle light scattering (SEC-MALS) and capillary viscometry. HA and TSP were found to have ) kg/mol and ) kg/mol respectively, and and ml/g, respectively. The structure of HA ranges from a rodlike molecule at lower molar masses changing to a random coil for Mw > 800 kg/mol, based on the Mark-Houwink-Kuhn-Sakurada (MHKS) coefficient. TSP, by contrast, is a random coil across the range of molar masses. For the mixed HA-TSP systems, SEC-MALS indicates a weak interaction. However, sedimentation coefficient (s) distributions obtained from SV-AUC measurements together with intrinsic viscosity demonstrated no evidence of any significant aggregation phenomenon, reassuring in terms of eye-drop formulation technology involving these substances.