title: A quantitative assessment of inhaled drug particle-pulmonary surfactant interaction by atomic force microscopy.
abstract: To date limited consideration has been given to the physical interaction between inhaled drug particles and pulmonary surfactant (PS). This study combines atomic force microscopy (AFM) with a Langmuir-Blodgett (LB) approach to quantify the force of adhesion between micronised budesonide particles and simulated PS monolayers. A LB approach was used to prepare Survanta monolayers at pre-determined surface pressures and AFM was employed to facilitate their visualisation. Adhesion measurements between drug particles and PS monolayers were executed via AFM. Contact angle measurements were performed to probe material wetting characteristics, the data confirmed that budesonide is hydrophobic and Survanta films at increasing surface pressure exhibit a rising hydrophobic character. AFM revealed that PS properties were governed by applied surface pressure and that the degree of interaction of budesonide was greater at higher surface pressure, where packing of the lipid film was increased; consistent with the point of exhalation. This correlates well with the accepted inhaler technique. The increasing hydrophobicity of the PS film, on increased pressure, was believed to be the primary reason for increased interaction with the hydrophobic budesonide. Surface chemistries of the drug particles and PS interface are considered to be important for inhaled drug delivery.
authors.affiliation: The School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK. m.davies1@ljmu.ac.uk
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
authors.forename: Anne
authors.initials: A
authors.lastname: Brindley
authors.forename: Xinyong
authors.initials: X
authors.lastname: Chen
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Doughty
authors.forename: Maria
authors.initials: M
authors.lastname: Marlow
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Roberts
mesh_terms: D000280:Administration, Inhalation; D000327:Adsorption; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry*; D019819:Budesonide / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D018625:Microscopy, Atomic Force / Q000379:methods*; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011663:Pulmonary Surfactants / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D001993:Bronchodilator Agents; D011663:Pulmonary Surfactants; D019819:Budesonide