title: Lyophilized inserts for nasal administration harboring bacteriophage selective for Staphylococcus aureus: in vitro evaluation.
abstract: Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) poses an infection risk and eradication during hospitalization is recommended. Bacteriophage therapy may be effective in this scenario but suitable nasal formulations have yet to be developed. Here we show that lyophilization of bacteriophages in 1ml of a viscous solution of 1-2% (w/v) hydroxypropyl methylcellulose (HPMC) with/without the addition of 1% (w/v) mannitol, contained in Eppendorf tubes, yields nasal inserts composed of a highly porous leaflet-like matrix. Fluorescently labeled bacteriophage were observed to be homogenously distributed throughout the wafers of the dried matrix. The bacteriophage titer fell 10-fold following lyophilization to 10(8)pfu per insert, then falling a further 100- to 1000-fold over 6 to 12months storage at 4°C. This compares well with a total dose of 6×10(5)pfu in 0.2ml liquid applied into the ear during a recent clinical trial in humans. The residual water content of the lyophilized inserts was reduced upon the addition of mannitol to HPMC, but this did not have any correlation to the lytic activity. Mannitol underwent a transition from its amorphous to crystalline state during exposure of the inserts to increasing relative humidities (as would be experienced in the nose), although this transition was suppressed by higher HPMC concentrations and the presence of buffer containing gelatin and bacteriophages. Our results therefore suggest that lyophilized inserts harboring bacteriophage selective for S. aureus may be a novel means for the eradication of MRSA resident in the nose.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK.
authors.forename: Munerah
authors.initials: M
authors.lastname: Alfadhel
authors.forename: Utsana
authors.initials: U
authors.lastname: Puapermpoonsiri
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ford
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: McInnes
authors.forename: Christopher F
authors.initials: CF
authors.lastname: van der Walle
mesh_terms: D000042:Absorption; D000281:Administration, Intranasal; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004343:Drug Implants / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D005612:Freeze Drying / Q000379:methods*; D006801:Humans; D065347:Hypromellose Derivatives; D008353:Mannitol / Q000737:chemistry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000821:virology; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D013203:Staphylococcal Infections / Q000628:therapy / Q000821:virology; D017108:Streptococcus Phages / Q000737:chemistry* / Q000254:growth & development; D013499:Surface Properties; D014867:Water / Q000378:metabolism*
chemical_list: D004343:Drug Implants; D014867:Water; D065347:Hypromellose Derivatives; D008353:Mannitol; D008747:Methylcellulose