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

Abstract

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.

KEY WORDS

liposome powder protein pulmonary rSLPI 

Abbreviations

ACI

Andersen cascade impactor

Anti-NE

Anti-neutrophil elastase

Cat L

Cathepsin L

CFCs

Chlorofluorocarbons

Chol

Cholesterol

DOPS

1,2-Dioleoyl-sn-glycero-3-[phospho-L-serine]

DOPS–rSLPI

rSLPI encapsulated in DOPS/Chol liposomes

DPI

Dry powder inhaler

ED

Emitted dose

FPF

Fine particle fraction

GSD

Geometric standard deviation

MMAD

Mass median aerodynamic diameter

NE

Neutrophil elastase

NRF

Non-respirable fraction

SEM

Scanning electron microscopy

rSLPI

Recombinant secretory leukocyte protease inhibitor

SLPI

Secretory leukocyte protease inhibitor

TSI

Twin stage impinger

Notes

Acknowledgements

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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