A dual action of D-amino acids on anti-biofilm activity and moisture-protection of inhalable ciprofloxacin powders.

Autor: Chang RYK; Advanced Drug Delivery Group, Faculty of Medicine and Health, School of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: yoon.chang@sydney.edu.au., Li M; Advanced Drug Delivery Group, Faculty of Medicine and Health, School of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: meli3816@uni.sydney.edu.au., Chow MYT; Advanced Drug Delivery Group, Faculty of Medicine and Health, School of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: yee.chow@sydney.edu.au., Ke WR; School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: weke4500@uni.sydney.edu.au., Tai W; Advanced Drug Delivery Group, Faculty of Medicine and Health, School of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: wtai6746@uni.sydney.edu.au., Chan HK; Advanced Drug Delivery Group, Faculty of Medicine and Health, School of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: kim.chan@sydney.edu.au.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2022 Apr; Vol. 173, pp. 132-140. Date of Electronic Publication: 2022 Mar 18.
DOI: 10.1016/j.ejpb.2022.03.003
Abstrakt: Although inhalation powder aerosols of antibiotics have been used to treat respiratory infections caused by Pseudomonas aeruginosa, biofilms are difficult to clear. Ciprofloxacin and D-amino acids (D-Met, D-Trp and D-Phe) were shown to facilitate P. aeruginosa biofilm removal. Spray dried powders for inhalation tend to be amorphous, hence unstable to moisture which causes deterioration in the aerosol performance. Hydrophobic L-amino acids such as leucine can impart moisture protection. In this study, we hypothesized that co-spray dried formulations of ciprofloxacin and hydrophobic D-amino acids will offer the combined benefits of both anti-biofilm and moisture protection properties. Of the three D-amino acids tested, D-Met and D-Trp (at 5 mM) but not D-Phe reduced clinical isolate P. aeruginosa biofilm loads and the extent of biofilm clearance was further enhanced in the presence of ciprofloxacin. Subsequently, ciprofloxacin was spray dried alone or in combination with 30% (w/w) D-Met or D-Trp. The biological and physicochemical properties of the powders were assessed, including the minimum inhibitory concentration, anti-biofilm activity, particle size distribution and morphology, solid-state properties, water sorption, and aerosol performance. The spray dried combination powders were physically stable and inhalable with fine particle fraction (<5 µm) values of 50-57% when aerosolized. The powders exhibited enhanced anti-biofilm activity compared with ciprofloxacin alone. The presence of D-amino acids provided moisture protection, with the recrystallization event shifting from 50% RH to 80% RH in powders containing D-Trp. In conclusion, the use of D-amino acids (D-Met or D-Trp) is an attractive formulation strategy which offers dual benefits of anti-biofilm effect and moisture protection.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: