Hydrogel Antimicrobial Capture Coatings for Endotracheal Tubes: A Pharmaceutical Strategy Designed to Prevent Ventilator-Associated Pneumonia

• Published in: Molecular pharmaceutics 2015-08, Vol.12 (8), p.2928-2936
• Main Authors: Jones, David S, McCoy, Colin P, Andrews, Gavin P, McCrory, Roisin M, Gorman, Sean P
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Biocompatible Materials - chemistry; Gentamicins - pharmacology; Humans; Hydrogels - chemistry; Intubation, Intratracheal; Kinetics; Pneumonia, Ventilator-Associated - microbiology; Pneumonia, Ventilator-Associated - prevention & control; Polymers - chemistry; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Staphylococcus aureus; Staphylococcus aureus - drug effects; Surface-Active Agents - chemistry; Temperature; Tensile Strength
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.5b00208

This paper presents a novel strategy for the prevention of ventilator-associated pneumonia that involves coating poly­(vinyl chloride, PVC) endotracheal tubes (ET) with hydrogels that may be subsequently used to entrap nebulized antimicrobial solutions. Candidate hydrogels were prepared containing a range of ratios of hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) from 100:0 to 70:30 using free radical polymerization and, when required, simultaneous attachment to PVC was performed. The mechanical properties, glass transition temperatures, swelling kinetics, uptake of gentamicin from an aqueous medium, and gentamicin release were characterized. Increasing the MAA content of the hydrogels significantly decreased the ultimate tensile strength, % elongation at break, Young’s modulus, and increased the glass transition temperature, the swelling ratio, and gentamicin uptake. Microbial (Staphylococcus aureus and Pseudomonas aeruginosa) adherence to control (drug-free) hydrogels was observed; however, while adherence to gentamicin-containing p­(HEMA) occurred, no adherence occurred to gentamicin-containing HEMA:MAA copolymers. Antimicrobial persistence of gentamicin-containing hydrogels was examined by determining the zone of inhibition against each microorganism on successive days. Hydrogel composition affected the observed antimicrobial persistence, with the hydrogel composed of 70:30 HEMA:MAA exhibiting >20 days persistence against S. aureus and P. aeruginosa, respectively. To simulate clinical use, the hydrogels (coated onto PVC) were first exposed to a nebulized solution of gentamicin (4 mL, 80 mg for 20 min), and then to nebulized bacteria (4 mL ca. 1 × 109 colony forming units mL–1, 30 min). Viable bacteria were not observed on the gentamicin-treated p­(HEMA: MAA) copolymers, whereas growth was observed on gentamicin-treated p­(HEMA). In light of the excellent antimicrobial activity and physicochemical properties, p­(HEMA: MAA) copolymers composed of ratios of 80:20 or 70:30 HEMA: MAA were identified as potentially useful coatings of endotracheal tubes to be used in conjunction with the clinical nebulization of gentamicin and designed for the prevention of ventilator-associated pneumonia.