Effects of storage conditions on the stability of spray dried, inhalable bacteriophage powders

Leung, Sharon Shui Yee; Parumasivam, Thaigarajan; Gao, Fiona; Carter, Elizabeth A.; Carrigy, Nicholas B.; Vehring, Reinhard; Finlay, Warren H.; Morales, Sandra; Britton, Warwick J.; Kutter, Elizabeth; Chan, Hak‐Kim

doi:10.1016/j.ijpharm.2017.01.060

Cited by 84 publications

(105 citation statements)

References 33 publications

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“…Lactose and trehalose are commonly used as a protein stabiliser [24, 25, 31]. In particular, trehalose is known for its exceptional phage stabilising properties [32] and its ability to protect biomaterials from thermal stress and dehydration [33, 34]. Protein protection is generally believed to be via the mechanism of water replacement and/or vitrification [35].…”

Section: Discussionmentioning

confidence: 99%

“…10). Provided storage at low RH (<22% RH) can be achieved (e.g., in heat-sealed aluminium foil or under vacuum), the formulation would likely have sufficient physical and biological stability for ≥ 12 months [32]. However, long-term safety concerns arising from pulmonary delivery of large amount of leucine and sugar remain to be addressed.…”

Section: Discussionmentioning

confidence: 99%

“…Use of low inlet temperature is critical for retaining phage bioactivity during spray drying, which in turn may also lead to increased residual moisture content in the powder. A recent work from our group has assessed the stability of phage PEV2 spray dried powders at low inlet temperature of 60°C [32]. The biological and physicochemical stability of the formulations were maintained after storage at 0 and 22% relative humidity at 4°C for 12 months.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

Chang

Wong

Mathai

et al. 2017

European Journal of Pharmaceutics and Biopharmaceutics

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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 85 L/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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Chang

Wong

Mathai

et al. 2017

European Journal of Pharmaceutics and Biopharmaceutics

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“…Delivering them as aerosols can achieve direct targeting in the lungs. The feasibility of bioengineering phages into inhalable powders by spray drying has been demonstrated in vitro 1‐6 along with efficacy studies in vivo 7,8 . In the production process, it is essential to preserve phage bioactivity in the dry state by suitable excipients.…”

Section: Introductionmentioning

confidence: 99%

Inhalable bacteriophage powders: Glass transition temperature and bioactivity stabilization

Chang

Kwok

Khanal

et al. 2020

Bioengineering & Transla Med

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Recent heightened interest in inhaled bacteriophage (phage) therapy for combating antibacterial resistance in pulmonary infections has led to the development of phage powder formulations. Although phages have been successfully bioengineered into inhalable powders with preserved bioactivity, the stabilization mechanism is yet unknown. This paper reports the first study investigating the stabilization mechanism for phages in these powders. Proteins and other biologics are known to be preserved in dry state within a glassy sugar matrix at storage temperatures (T s ) at least~50 C below the glass transition temperature (T g ). This is because at (T g − T s ) >50 C, molecules are sufficiently immobilized with reduced reactivity. We hypothesized that this glass stabilization mechanism may also be applicable to phages comprising mostly of proteins. In this study, spray dried powders of Pseudomonas phage PEV20 containing lactose and leucine as excipients were stored at 5, 25 or 50 C and 15 or 33% relative humidity (RH), followed by assessment of bioactivity (PEV20 stability) and physical properties. PEV20 was stable with negligible titer loss after storage at 5 C/15% RH for 250 days, while storage at 33% RH caused increased titer losses of 1 log 10 and 3 log 10 at 5 and 25 C, respectively. The plasticizing effect of water at 33% RH lowered the T g by 30 C, thus narrowing the gap between T s and T g to 19-28 C, which was insufficient for glass stabilization. In contrast, the (T g − T s ) values were higher (range, 46-65 C) under the drier condition of 15% RH, resulting in the improved stability which corroborated with the vitrification hypothesis. Furthermore, phage remained stable (≤1 log 10 ) when the (T g − T s ) value lay between 26-48 C, but became inactivated as the value fell below 20 C. In conclusion, this study demonstrated that phage can be sufficiently stabilized in spray dried powders by keeping Abbreviations: DSC, differential scanning calorimetry; RH, relative humidity; TGA, thermal gravimetric analysis.; XRD, X-ray diffraction pattern.

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“…Liquid phage formulations have a short shelf life. Currently, scientists are trying to use phages in a much more stable form as dried powder specially for pulmonary infections having a longer shelf life with ease to store, transport, and administer . Transdermal delivery of phages provides another stable and effective route of administration .…”

Section: Why Phage Therapy?mentioning

confidence: 99%

The dawn of phage therapy

Rehman

Ali

Khan

et al. 2019

Reviews in Medical Virology

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Bacteriophages or phages, being the most abundant entities on earth, represent a potential solution to a diverse range of problems. Phages are successful antibacterial agents whose use in therapeutics was hindered by the discovery of antibiotics. Eventually, because of the development and spread of antibiotic resistance among most bacterial species, interest in phage as therapeutic entities has returned, because their noninfectious nature to humans should make them safe for human nanomedicine.This review highlights the most recent advances and progress in phage therapy and bacterial hosts against which phage research is currently being conducted with respect to food, human, and marine pathogens. Bacterial immunity against phages and tactics of phage revenge to defeat bacterial defense systems are also summarized.We have also discussed approved phage-based products (whole phage-based products and phage proteins) and shed light on their influence on the eukaryotic host with respect to host safety and induction of immune response against phage preparations.Moreover, creation of phages with desirable qualities and their uses in cancer treatment, vaccine production, and other therapies are also reviewed to bring together evidence from the scientific literature about the potentials and possible utility of phage and phage encoded proteins in the field of therapeutics and industrial biotechnology.

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Effects of storage conditions on the stability of spray dried, inhalable bacteriophage powders

Cited by 84 publications

References 33 publications

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

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

Inhalable bacteriophage powders: Glass transition temperature and bioactivity stabilization

The dawn of phage therapy

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