AAPS PharmSciTech

, Volume 11, Issue 3, pp 1411–1421

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

DOI: 10.1208/s12249-010-9500-2

Cite this article as:
Gibbons, A., McElvaney, N.G. & Cryan, S. AAPS PharmSciTech (2010) 11: 1411. doi:10.1208/s12249-010-9500-2

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

liposomepowderproteinpulmonaryrSLPI

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

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