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The use of amino acids to enhance the aerosolisation of spray‐dried powders for pulmonary gene therapy
Author(s) -
Li H.Y.,
Seville P. C.,
Williamson I. J.,
Birchall J. C.
Publication year - 2005
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.654
Subject(s) - amino acid , spray drying , chemistry , in vitro , arginine , phenylalanine , inhalation , aspartic acid , viability assay , transfection , zeta potential , chromatography , biochemistry , medicine , materials science , gene , nanotechnology , nanoparticle , anatomy
Background Pulmonary delivery of gene therapy offers the potential for the treatment of a range of lung conditions, including cystic fibrosis, asthma and lung cancer. Spray‐drying may be used to prepare dry powders for inhalation; however, aerosolisation of such powders is limited, resulting in poor lung deposition and biological functionality. In this study, we examine the use of amino acids (arginine, aspartic acid, threonine, phenylalanine) to enhance the aerosolisation of spray‐dried powders containing model non‐viral gene vectors. Methods Lipid/polycation/pDNA (LPD) vectors, in the presence or absence of amino acids, were dispersed in lactose solutions, and spray‐dried to produce appropriately sized dry powders. Scanning electron microscopy and laser diffraction were used to determine particle morphology and diameter, respectively. Gel electrophoresis was used to examine the influence of amino acids on the structural integrity of the LPD complex. In vitro cell (A549) transfection was used to determine the biological functionality of the dry powders, and the in vitro aerosolisation performance was assessed using a multistage liquid impinger (MSLI). Results Both gel electrophoresis and in vitro cell transfection indicated that certain amino acids (aspartic acid, threonine) can adversely affect the integrity and biological functionality of the LPD complex. All amino acids significantly increased the aerosolisation of the powder, with the arginine and phenylalanine powders showing optimal deposition in the lower stages of the MSLI. Conclusions Amino acids can be used to enhance the aerosolisation of spray‐dried powders for respiratory gene delivery, allowing the development of stable and viable formulations for pulmonary gene therapy. Copyright © 2004 John Wiley & Sons, Ltd.