AAPS PharmSciTech

, Volume 11, Issue 3, pp 1411–1421 | Cite as

A Dry Powder Formulation of Liposome-Encapsulated Recombinant Secretory Leukocyte Protease Inhibitor (rSLPI) for Inhalation: Preparation and Characterisation

  • Aileen Gibbons
  • Noel G. McElvaney
  • Sally-Ann Cryan
Research Article


Inhaled recombinant secretory leukocyte protease inhibitor (rSLPI) has shown potential for the treatment of inflammatory lung conditions. Rapid inactivation of rSLPI by cathepsin L (Cat L) and rapid clearance from the lungs has limited clinical efficacy to date. Previous studies by us have shown that encapsulation of rSLPI within1,2-dioleoyl-sn-glycero-3-[phospho-L-serine]/cholesterol (DOPS/Chol) liposomes protects rSLPI against Cat L inactivation in vitro. Liquid DOPS–rSLPI preparations were found to be unstable upon long-term storage and nebulisation. The aim of this study was therefore to develop a method of manufacture for preparing DOPS–rSLPI liposomes as a dry powder for inhalation. DOPS–rSLPI dry powders were lyophilised and subsequently micronised with a novel micronisation aid. The effects of formulation and processing on rSLPI stability, activity, and uniformity of content within the powders were characterised. Using D-mannitol as the micronisation aid, dry powder particles in the inhalable size range (<5 μm) were prepared. By optimising process parameters, up to 54% of rSLPI was recovered after micronisation, of which there was no significant loss in anti-neutrophil elastase activity and no detectable evidence of protein degradation. Aerosolisation was achieved using a dry powder inhaler, and mass median aerodynamic diameter (MMAD) was evaluated after collection in a cascade impactor. Aerosolisation of the DOPS–rSLPI dry powder yielded 38% emitted dose, with 2.44 μm MMAD. When challenged with Cat L post-aerosolisation, DOPS–rSLPI dry powder was significantly better at retaining a protective function against Cat L-induced rSLPI inactivation compared to the aqueous DOPS–rSLPI liposome dispersion and was also more stable under storage.


liposome powder protein pulmonary rSLPI 



Andersen cascade impactor


Anti-neutrophil elastase

Cat L

Cathepsin L








rSLPI encapsulated in DOPS/Chol liposomes


Dry powder inhaler


Emitted dose


Fine particle fraction


Geometric standard deviation


Mass median aerodynamic diameter


Neutrophil elastase


Non-respirable fraction


Scanning electron microscopy


Recombinant secretory leukocyte protease inhibitor


Secretory leukocyte protease inhibitor


Twin stage impinger



This study was funded by the Irish Research Council for Science, Engineering and Technology (SC/2004/B0419) and the Health Research Board (HRB). The authors gratefully acknowledge the supply of rSLPI from Amgen®.


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Copyright information

© American Association of Pharmaceutical Scientists 2010

Authors and Affiliations

  • Aileen Gibbons
    • 1
  • Noel G. McElvaney
    • 2
  • Sally-Ann Cryan
    • 1
  1. 1.School of PharmacyRoyal College of Surgeons in IrelandDublin 2Ireland
  2. 2.Department of MedicineBeaumont Hospital, Royal College of Surgeons in IrelandDublinIreland

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