Instability of bacteriophages in spray-dried trehalose powders is caused by crystallization of the matrix

Vandenheuvel, Dieter; Meeus, Joke; Lavigne, Rob; Mooter, Guy Van den

doi:10.1016/j.ijpharm.2014.06.026

Cited by 78 publications

(66 citation statements)

References 10 publications

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“…The enhanced specific surface area could increase the rate of moisture sorption and cause recrystallization of the trehalose component during the measurement, accounting for the stronger crystallinity. Vandenheuvel et al [32] reported that high humidity (54% RH) could cause crystallization of the spray dried trehalose powder matrix.…”

Section: Resultsmentioning

confidence: 99%

“…Most phage research for respiratory infections in the past has been confined to liquid aerosols using intranasal instillation [13, 16, 17, 26] and nebulization [12, 27, 28]. Few studies have examined formulating phages into inhalable dry powder form for ease of storage, transport and administration [29–32]. …”

Section: Introductionmentioning

confidence: 99%

“…They also reported that trehalose was more efficient in preventing phages from inactivation during the production process, compared with lactose and dextran 35. Their subsequent study [32], however, highlighted the importance of suitable storage conditions in preserving the stability of phages embedded in the spray dried trehalose powders.…”

Section: Introductionmentioning

confidence: 99%

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Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections

et al. 2016

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Purpose The potential of aerosol phage therapy for treating lung infections has been demonstrated in animal models and clinical studies. This work compared the performance of two dry powder formation techniques, spray freeze drying (SFD) and spray drying (SD), in producing inhalable phage powders. Method A Pseudomonas podoviridae phage, PEV2, was incorporated into multi-component formulation systems consisting of trehalose, mannitol and L-leucine (F1 = 60:20:20 and F2 = 40:40:20). The phage titer loss after the SFD and SD processes and in vitro aerosol performance of the produced powders were assessed. Results A significant titer loss (~ 2 log) was noted for droplet generation using an ultrasonic nozzle employed in the SFD method, but the conventional two-fluid nozzle used in the SD method was less destructive for the phage (~0.75 log loss). The phage were more vulnerable during the evaporative drying process (~0.75 log further loss) compared with the freeze drying step, which caused negligible phage loss. In vitro aerosol performance showed that the SFD powders (~80% phage recovery) provided better phage protection than the SD powders (~20% phage recovery) during the aerosolization process. Despite this, higher total lung doses were obtained for the SD formulations (SD-F1 = 13.1 ± 1.7 × 104 pfu and SD-F2 = 11.0 ± 1.4 × 104 pfu) than from their counterpart SFD formulations (SFD-F1 = 8.3 ± 1.8 × 104 pfu and SFD-F2 = 2.1 ± 0.3 × 104 pfu). Conclusion Overall, the SD method caused less phage reduction during the powder formation process and the resulted powders achieved better aerosol performance for PEV2.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections

et al. 2016

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“…As a result, most phage research for respiratory infections in the past has been confined to liquid aerosols using intranasal instillation (Carmody et al., 2010; Debarbieux et al, 2010; Morello et al, 2011; Alemayehu et al, 2012; Semler et al, 2014) and nebulisation (Sahota et al, 2015; Abedon, 2015). Since many bacteriophage strains may be stabilised in the powder form for years and so facilitate their global distribution (Golshahi et al, 2011), recent efforts have been devoted to develop stabilised dry dosage formulations for phage inhalation (Golshahi et al, 2011; Matinkhoo et al, 2011; Vandenheuvel et al., 2013, 2014; Leung et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

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

Leung

Parumasivam

Gao

et al. 2017

International Journal of Pharmaceutics

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This study aimed to develop inhalable powders containing phages active against antibiotic-resistant Pseudomonas aeruginosa for pulmonary delivery. A Pseudomonas phage, PEV2, was spray dried into powder matrices comprising of trehalose (0–80%), mannitol (0–80%) and L-leucine (20%). The resulting powders were stored at various relative humidity (RH) conditions (0, 22 and 60% RH) at 4 °C. The phage stability and in vitro aerosol performance of the phage powders were examined at the time of production and after 1, 3 and 12 months storage. After spray drying, a total of 1.3 log titer reduction in phage was observed in the formulations containing 40%, 60% and 80% trehalose, whereas 2.4 and 5.1 log reductions were noted in the formulations containing 20% and no trehalose, respectively. No further reduction in titer occurred for powders stored at 0 and 22% RH even after 12 months, except the formulation containing no trehalose. The 60% RH storage condition had a destructive effect such that no viable phages were detected after 3 and 12 months. When aerosolised, the total lung doses for formulations containing 40%, 60% and 80% trehalose were similar (in the order of 105 pfu). The results demonstrated that spray drying is a suitable method to produce stable phage powders for pulmonary delivery. A powder matrix containing ≥ 40% trehalose provided good phage preservation and aerosol performances after storage at 0 and 22 % RH at 4 °C for 12 months.

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“…Peynir alt› suyu tozu ile uygulanan mikroenkapsülayon iflleminde ise, 4°C'de karanl›k ortamda depolanan fajlar›n aktivasyonunda 1 ayl›k depolama süresince azalma olmad›¤› bildirilmifltir. Sonuç olarak, söz konusu araflt›rmada ve benzer çal›flmalarda tedavi amac›yla uygulanacak olan fajlar›n depolama koflullar›n›n dikkate al›nmas› gereken önemli parametreler oldu¤u bildirilmifltir (35)(36)(37). A¤›z yoluyla uygulanan faj tedavilerinde asidik çevre koflular›nda ve baz› enzimlerin varl›¤›nda fajlar›n aktivitelerinde azalma gözlenmifltir.…”

Section: Bakteri̇yofaj Enkapsülasyonu Potansi̇yel Uygulamalariunclassified

Bakteri̇yofaj Enkapsülasyonu Ve Potansi̇yel Uygulamalari

Saygılı¹,

Karagözlü²

2017

GIDA

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ÖzetEnkapsülasyon, aktif olan maddenin çevresinde uygun kaplama materyali ile koruyucu bir zar oluflturulmas› temeline dayanmaktad›r. G›da endüstrisinde mikroenkapsülasyon istenen bileflenin d›fl etkenlere karfl› korunmas›, baz› özelliklerinin sürdürülebilmesi, kolay tafl›nmas›, tat ve koku maskeleme, oluflabilecek reaksiyonlar›n önüne geçme gibi amaçlarla kullan›lmas›na ra¤men koruyucu ve tedavi amaçl› fajlar›n enkapsülasyonunun da oldukça etkili bir yöntem olarak uygulanabildi¤i bilinmektedir. Bakteriyofajlar 20. yüzy›l›n bafllar›ndan beri bakteriyel enfeksiyonlara karfl› koruma ve tedavi amac›yla kullan›lm›fl ancak artan antibiyotik tüketimi, fajlar›n tedavi amaçl› kullan›m›n›n önüne geçmifltir. En önemli özelli¤i yüksek spesifitesi olan bakteriyofajlar, çiftlik hayvanlar›nda patojen kolonizasyonunun azalt›lmas› (faj tedavisi), çi¤ süt, et ve taze g›dalarda dekontaminasyon (biyokontrol), ekipman yüzeylerinde sanitasyon (biyosanitasyon), haz›r g›dalarda raf ömrü uzatmak (biyoprezervasyon) amac›yla uygulanabilen etkin bir yöntem olarak karfl›m›za ç›kmaktad›r. Bakteriyofaj enkapsülasyon uygulamalar›nda, fonksiyonel kaplama uygulamalar›ndaki geliflmelere paralel olarak daha uygun maliyetli ve daha uzun süre muhafaza edilebilen mikrokapsül teknolojilerinin gelifltirilmesine ihtiyaç duyulmaktad›r.Anahtar kelimeler: Enkapsülasyon, bakteriyofaj, faj tedavi, biyokontrol, biyosanitasyon, biyoprezervasyon BACTERIOPHAGE ENCAPSULATION AND POTENTIAL APPLICATIONS AbstractEncapsulation is based on forming a protective membrane around the active substance with a suitable coating material. Although microencapsulation is applied for purposes including protection of some components against external factors, preservation of some features, easy handling, flavor and odor masking, prevention of some reactions, it is known that the phage encapsulation can be highly effective for protection and treatment purposes. Since the early 20th century, bacteriophages are used for the prevention and treatment of bacterial infections, however the increase in the consumption of antibiotics has prevented the use of phages for treatment. One of the most important properties of bacteriophages is the high specificity. They are effectively used for the reduction of pathogen colonization in farm animals (phage therapy), decontamination of raw milk, meat and fresh food (biocontrol), sanitation of equipment surfaces (biosanitation), extending the shelf life of prepared foods (biopreservation). There is a need for the development of microcapsule technology which is relatively cost effective and allows longer storage periods in parallel with the developments in functional coating applications.

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Instability of bacteriophages in spray-dried trehalose powders is caused by crystallization of the matrix

Cited by 78 publications

References 10 publications

Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections

Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections

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

Bakteri̇yofaj Enkapsülasyonu Ve Potansi̇yel Uygulamalari

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