Bacteriophage formulated into a range of semisolid and solid dosage forms maintain lytic capacity against isolated cutaneous and opportunistic oral bacteria

Brown, Teagan L.; Thomas, Tereen; Odgers, Jessica; Petrovski, Steve; Spark, M. Joy; Tucci, Joseph

doi:10.1111/jphp.12673

Cited by 31 publications

(53 citation statements)

References 28 publications

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“…Similarly in neonates, skin based administration may act to protect the infant's fragile skin and prevent colonization by pathogens. Such applications may come in the form of phage-impregnated gels, creams and pessaries, all of which have retained phage activity in such formulations as previously demonstrated (Brown et al, 2017 ).…”

Section: Route Of Administration and Transfermentioning

confidence: 95%

Applications for Bacteriophage Therapy during Pregnancy and the Perinatal Period

2018

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Pregnant women and their unborn children are a population that is particularly vulnerable to bacterial infection. Physiological changes that occur during pregnancy affect the way women respond to such infections and the options that clinicians have for treatment. Antibiotics are still considered the best option for active infections and a suitable prophylaxis for prevention of potential infections, such as vaginal/rectal Streptococcus agalactiae colonization prior to birth. The effect of such antibiotic use on the developing fetus, however, is still largely unknown. Recent research has suggested that the fetal gut microbiota plays a critical role in fetal immunologic programming. Hence, even minor alterations in this microbiota may have potentially significant downstream effects. An ideal antibacterial therapeutic for administration during pregnancy would be one that is highly specific for its target, leaving the surrounding microbiota intact. This review first provides a basic overview of the challenges a clinician faces when administering therapeutics to a pregnant patient and then goes on to explore common bacterial infections in pregnancy, use of antibiotics for treatment/prevention of such infections and the consequences of such treatment for the mother and infant. With this background established, the review then explores the potential for use of bacteriophage (phage) therapy as an alternative to antibiotics during the antenatal period. Many previous reviews have highlighted the revitalization of and potential for phage therapy for treatment of a range of bacterial infections, particularly in the context of the increasing threat of widespread antibiotic resistance. However, information on the potential for the use of phage therapeutics in pregnancy is lacking. This review aims to provide a thorough overview of studies of this nature and discuss the feasibility of bacteriophage use during pregnancy to treat and/or prevent bacterial infections.

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Section: Route Of Administration and Transfermentioning

confidence: 95%

Applications for Bacteriophage Therapy during Pregnancy and the Perinatal Period

2018

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“…The process is an effective way to enhance the equal distribution of the API within the blend, and an increase in mixing time promotes better distribution of the active ingredient [ 30 ]. In the formulation of small volumes of concentrated phage solution into semi-solid vehicles, as reported by Brown et al [ 31 ], the process involves the addition, mixing (for at least five minutes) and even distribution of the phage solution into a small portion (approximately 1–2 g) of the semi-solid vehicle, then thorough mixing (for at least five minutes) of this small portion with an equal mass of fresh vehicle. This process is repeated until all the fresh cream has been incorporated, and ensures that the medicament (in this case, the phage) is evenly dispersed throughout the cream.…”

Section: Formulations Of Semi-solid and Solid Dosage Forms For Delmentioning

confidence: 99%

“…The numbers of active phage particles can then be determined by serial dilution and counting of plaques on a bacterial lawn [ 37 ]. One of the issues, however, is that such a method relies on the miscibility of all the components of the semi-solid preparations in the solvent, and so may be more suitable for phage formulations in more hydrophilic creams [ 31 ]. The use of a benign aqueous solvent (e.g., water, physiological saline or phosphate buffered saline (PBS)) is important here, as other solvents may prove toxic to bacteria growing on agar plates or the phages contained in the formulation.…”

Section: Stability Of Phages In Semi-solid Preparationsmentioning

confidence: 99%

“…The quantitative assessment of phage stability and lytic activity over time (determined by counting of plaques following mixing of small amounts of phage cream 1:100 into PBS, as described above), were employed for Propionibacterium acnes Siphoviridae phages formulated into more hydrophilic cream bases (cetomacrogol cream aqueous, aqueous cream, and cetrimide cream aqueous) [ 31 ]. These assessments showed that storing the formulations at 4 °C in light-protected containers resulted in the greatest levels of viable P .…”

Section: Stability Of Phages In Semi-solid Preparationsmentioning

confidence: 99%

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Semi-Solid and Solid Dosage Forms for the Delivery of Phage Therapy to Epithelia

et al. 2018

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The delivery of phages to epithelial surfaces for therapeutic outcomes is a realistic proposal, and indeed one which is being currently tested in clinical trials. This paper reviews some of the known research on formulation of phages into semi-solid dosage forms such as creams, ointments and pastes, as well as solid dosage forms such as troches (or lozenges and pastilles) and suppositories/pessaries, for delivery to the epithelia. The efficacy and stability of these phage formulations is discussed, with a focus on selection of optimal semi-solid bases for phage delivery. Issues such as the need for standardisation of techniques for formulation as well as for assessment of efficacy are highlighted. These are important when trying to compare results from a range of experiments and across different delivery bases.

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“…We and others have reported the potential of semi-solid preparations for the delivery of phages [ 26 – 28 ]. More recently we tested the efficacy, stability and optimal storage conditions of a range of semi-solid and solid dosage forms for the delivery of lytic phages in an in-vitro model [ 29 ]. While several phages that are capable of lysing K .…”

Section: Introductionmentioning

confidence: 99%

Characterization and formulation into solid dosage forms of a novel bacteriophage lytic against Klebsiella oxytoca

et al. 2017

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AimTo isolate and characterize bacteriophage lytic for the opportunistic pathogen Klebsiella oxytoca and their formulation into a range of solid dosage forms for in-vitro testing.Methods and resultsWe report the isolation, genomic and functional characterization of a novel bacteriophage lytic for Klebsiella oxytoca, which does not infect the closely related Klebsiella pneumoniae. This bacteriophage was formulated into suppositories and troches and shown to be released and lyse underlying Klebsiella oxytoca bacteria in an in-vitro model. These bacteriophage formulations were stable for at least 49 days at 4°C.ConclusionsThe successful in-vitro assay of these formulations here suggests that they could potentially be tested in-vivo to determine whether such a therapeutic approach could modulate the gut microbiome, and control Klebsiella oxytoca overgrowth, during antibiotic therapy regimes.Significance and impact of the studyThis study reports a novel bacteriophage specific for Klebsiella oxytoca which can be formulated into solid dosage forms appropriate for potential delivery in testing as a therapy to modulate gut microbiome during antibiotic therapies.

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Bacteriophage formulated into a range of semisolid and solid dosage forms maintain lytic capacity against isolated cutaneous and opportunistic oral bacteria

Cited by 31 publications

References 28 publications

Applications for Bacteriophage Therapy during Pregnancy and the Perinatal Period

Applications for Bacteriophage Therapy during Pregnancy and the Perinatal Period

Semi-Solid and Solid Dosage Forms for the Delivery of Phage Therapy to Epithelia

Characterization and formulation into solid dosage forms of a novel bacteriophage lytic against Klebsiella oxytoca

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