Poly(ether-anhydride) dry powder aerosols for sustained drug delivery in the lungs

Abstract

A new family of biodegradable ether-anhydride polymers was used to develop microparticles capable of controlled drug release and inhalation as a dry powder. The polymers are composed of various ratios of sebacic acid (SA) (to render the polymer insoluble in water) and poly(ethylene glycol) (PEG) (to reduce particle clearance by macrophages and improve aerosolization). Particle aerodynamic diameter was controlled within the respirable range by producing geometrically large, but low density particles as a first step toward reducing particle adhesion forces that limit efficient aerosolization of dry powders. Particles made from a variety of polymer compositions possessed high emitted doses (>80%) from a Spinhaler dry powder inhaler (DPI). Control over particle surface and bulk properties (surface roughness, surface charge, density and water retention) was achieved by varying the percentage of PEG in the polymer backbone. The addition of 10% PEG into the polymer backbone significantly enhanced deposition in the lower stages of an in vitro lung model following aerosolization from the DPI (fine particle fractions [FPF] reached 30%). Efficient aerosolization from an obsolete DPI combined with the ability to evade phagocytic clearance and provide controlled release of various drug molecules make these particles promising for prolonged drug delivery in the lung. © 2004 Elsevier B.V. All rights reserved.