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Stability of bacteriophages in organic solvents for formulations.
Cao, Yue; Khanal, Dipesh; Kim, Jinhee; Chang, Rachel Yoon Kyung; Byun, Alex Seungyeon; Morales, Sandra; Banaszak Holl, Mark M; Chan, Hak-Kim.
Afiliación
  • Cao Y; Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, NSW 2006, Australia.
  • Khanal D; Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, NSW 2006, Australia.
  • Kim J; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
  • Chang RYK; Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, NSW 2006, Australia.
  • Byun AS; Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, NSW 2006, Australia.
  • Morales S; Phage Consulting, Sydney, New South Wales, NSW 2100, Australia.
  • Banaszak Holl MM; Department of Mechanical and Materials Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Division of Pulmonology, Allergy, and Critical Care Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Chan HK; Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, NSW 2006, Australia. Electronic address: kim.chan@sydney.edu.au.
Int J Pharm ; 646: 123505, 2023 Nov 05.
Article en En | MEDLINE | ID: mdl-37832702
Bacteriophages or phages used as an alternative therapy for treating multi-drug resistant infections require formulation consideration. Current strategies to produce phage formulations involving organic solvents are based on empirical practices without a good understanding of phage stability during formulation development. In this study, we investigated the effect of common formulation organic solvents (ethanol, isopropyl alcohol, tetrahydrofuran (THF) and dimethyl sulfoxide (DMSO)) on the stability of Pseudomonas aeruginosa-specific myovirus (PEV1, PEV20) and podovirus (PEV31) phages using biological assay, transmission electron microscopy (TEM) and scattering near field optical microscopy (SNOM). The three phages were mixed with the solvents at different concentrations (25%, 50%, and 75% (v/v)) for 20 min. All phages were fully viable in the organic solvents at 25% (v/v) showing negligible titre changes. At the higher solvent concentration of 50% (v/v), the myoviruses PEV1 and PEV20 remained relatively stable (titre loss 0.4-1.3 log10), whereas the podovirus PEV31 became less stable (titre loss 0.25-3.8 log10), depending on the solvent used. Increasing the solvent level to 75% (v/v) caused increased morphological changes in TEM and decreased viability as indicated by the titre loss (0.32-7.4 log10), with DMSO being the most phage-destabilising solvent. SNOM spectra showed differences in the signal intensity and peak positions in the amide I and amide II regions, revealing altered phage proteins by the solvents. In conclusion, the choice of the solvents for phage formulation depends on both the phages and solvent types. Our results showed (1) the phages are more stable in the alcohols than DMSO and THF, and (2) the myoviruses tend to be more stable than the podovirus in the solvents. Overall, a low to moderate (25-50 % v/v) level of organic solvents (except 50% THF) can be used in formulation of the phages without a substantial titre loss.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacteriófagos / Podoviridae Idioma: En Revista: Int J Pharm Año: 2023 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacteriófagos / Podoviridae Idioma: En Revista: Int J Pharm Año: 2023 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Países Bajos