Dataset Information

Production of highly stable spray dried phage formulations for treatment of Pseudomonas aeruginosa lung infection.

ABSTRACT: The potential of bacteriophage therapy for the treatment of pulmonary infections caused by antibiotic-resistant bacteria has been well recognised. The purpose of this study was to investigate the effect of excipients on stabilisation and aerosolisation of spray dried powders of morphologically different phages - PEV podovirus and PEV myovirus. Seven anti-pseudomonal phages were screened against 90 clinical strains of bacterial hosts and three of the phages were selected for formulation study based on the host range. Design of experiments was utilised to assess the effect of different excipients on the stabilisation and aerosolisation of spray dried phages. Both podovirus and myovirus phages were stable in spray dried formulations containing trehalose or lactose and leucine as excipients with less than 1-log10 titre reduction during spray drying, with lactose providing superior phage protection over trehalose. Furthermore, the spray dried phage formulations dispersed in an Osmohaler at 85L/min produced a high fine particle fraction of over 50%. The results showed that the phages in this study can form respirable dry powder phage formulations using the same excipient composition. Spray dried various types of lytic phages hold significant potential for the treatment of pulmonary infections.

SUBMITTER: Chang RY

PROVIDER: S-EPMC5650506 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Production of highly stable spray dried phage formulations for treatment of Pseudomonas aeruginosa lung infection.

Chang Rachel Y RY Wong Jennifer J Mathai Ash A Morales Sandra S Kutter Elizabeth E Britton Warwick W Li Jian J Chan Hak-Kim HK

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 20170907

The potential of bacteriophage therapy for the treatment of pulmonary infections caused by antibiotic-resistant bacteria has been well recognised. The purpose of this study was to investigate the effect of excipients on stabilisation and aerosolisation of spray dried powders of morphologically different phages - PEV podovirus and PEV myovirus. Seven anti-pseudomonal phages were screened against 90 clinical strains of bacterial hosts and three of the phages were selected for formulation study bas ...[more]

PMID: 28890220

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Project description:Trehalose is commonly used as a protein stabilizer in spray dried protein formulations delivered via the pulmonary route. Spray dried trehalose formulations are highly hygroscopic, which makes them prone to deliquescence and recrystallization when exposed to moisture, leading to impairment in aerosolization performance. The main aim of this study was to investigate and compare the effect of hydrophobic amino acids (i.e. L-leucine and L-isoleucine) in enhancing aerosolization performance and in mitigating moisture-induced changes in spray dried trehalose formulations. Trehalose was spray dried with 20-60% w/w of amino acid (i.e. L-leucine or L-isoleucine). The spray dried formulations were stored at 25?°C/50% RH for 28?days. Solid state characterization and in vitro aerosolization performance studies were performed on the spray dried formulations before and after storage. The addition of 20-60% w/w of amino acid (i.e. L-leucine or L-isoleucine) improved the emitted fractions of spray dried trehalose formulations from a dry powder inhaler. However, ? 40% w/w of L-leucine/L-isoleucine was needed to prevent recrystallization of trehalose in the formulations when exposed to 25?°C/50% RH for 28?days. X-ray photoelectron spectroscopy (XPS) demonstrated that samples with 40-60% w/w L-isoleucine had more amino acid on the surfaces of the particles compared to their L-leucine counterparts. This may explain the greater ability of the L-isoleucine (40-60% w/w) samples to cope with elevated humidity compared to L-leucine samples of the same concentrations, as observed in the dynamic vapour sorption (DVS) studies. In conclusion, this study demonstrated that both L-leucine and L-isoleucine were effective in enhancing aerosolization performance and mitigating moisture-induced reduction in aerosolization performance in spray dried trehalose formulations. L-isoleucine proved to be superior to L-leucine in terms of its moisture protectant effect when incorporated at the same concentration in the formulations.

Dataset Information

Production of highly stable spray dried phage formulations for treatment of Pseudomonas aeruginosa lung infection.

Publications

Production of highly stable spray dried phage formulations for treatment of Pseudomonas aeruginosa lung infection.

Similar Datasets

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