Miniature inhalation therapy platform using surface acoustic wave microfluidic atomization.

Pulmonary drug administration requires direct delivery of drug formulations into the lower pulmonary tract and alveoli of the lung in the form of inhaled particles or droplets, providing a distinct advantage over other methods for the treatment of respiratory diseases: the drug can be delivered directly to the site of inflammation, thus reducing the need for systemic exposure and the possibility of adverse effects. However, it is difficult to produce droplets of a drug solution within a narrow monodisperse size range (1-10 microm) needed for deposition in the lower pulmonary tract and alveoli. Here, we demonstrate the use of surface acoustic wave microfluidic atomization as an efficient means to generate appropriate aerosols containing a model drug, the short-acting beta2 agonist salbutamol, for the treatment of asthma. The mean aerosol diameter produced, 2.84+/-0.14 microm, lies well within the optimum size range, confirmed by a twin-stage impinger lung model, demonstrating that approximately 70 to 80% of the drug supplied to the atomizer is deposited within the lung. Our preliminary study explores how to control the aerosol diameter and lung delivery efficiency through the surface tension, viscosity, and input power, and also indicates which factors are irrelevant-like the fluid density. Even over a modest power range of 1-1.5 W, SAW atomization provides a viable and efficient generic nebulization platform for the delivery of drugs via the pulmonary route for the treatment of various diseases. The control offered over the aerosol size, low power requirements, high delivery efficiency, and the miniaturization of the system together suggest the proposed platform represents an attractive alternative to current nebulizers compatible with microfluidic technologies.

[1]  Leslie Y Yeo,et al.  Microparticle collection and concentration via a miniature surface acoustic wave device. , 2007, Lab on a chip.

[2]  P. Barnes New treatments for chronic obstructive pulmonary disease. , 2001, Current opinion in pharmacology.

[3]  A. James,et al.  The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics. , 1997, The European respiratory journal.

[4]  Anthony J. Hickey,et al.  Pharmaceutical Inhalation Aerosol Technology , 2003 .

[5]  M. Rahalkar,et al.  Chest , 2009, The Indian journal of radiology & imaging.

[6]  B. A. Rosenberg,et al.  The use of 2-ethylhexanol in acute pulmonary edema. , 1953, Diseases of the chest.

[7]  James Friend,et al.  Particle concentration and mixing in microdrops driven by focused surface acoustic waves , 2008 .

[8]  Leslie Y Yeo,et al.  Evaporative self-assembly assisted synthesis of polymeric nanoparticles by surface acoustic wave atomization , 2008, Nanotechnology.

[9]  J. M. Grace,et al.  A review of liquid atomization by electrical means , 1994 .

[10]  Leslie Y Yeo,et al.  Surface vibration induced spatial ordering of periodic polymer patterns on a substrate. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[11]  D. Geller Comparing clinical features of the nebulizer, metered-dose inhaler, and dry powder inhaler. , 2005, Respiratory care.

[12]  H. Frijlink,et al.  Dry powder inhalers for pulmonary drug delivery , 2004, Expert opinion on drug delivery.

[13]  G. W. Hallworth,et al.  The twin impinger: a simple device for assessing the delivery of drugs from metered dose pressurized aerosol inhalers , 1987, The Journal of pharmacy and pharmacology.

[14]  H. Marques,et al.  Complexation of Budesonide in Cyclodextrins and Particle Aerodynamic Characterization of the Complex Solid Form for Dry Powder Inhalation , 2002 .

[15]  M. Cloupeau,et al.  ELECTROHYDRODYNAMIC SPRAYING FUNCTIONING MODES - A CRITICAL-REVIEW , 1994 .

[16]  Robert Langer,et al.  Moving smaller in drug discovery and delivery , 2002, Nature Reviews Drug Discovery.

[17]  James Friend,et al.  Interfacial destabilization and atomization driven by surface acoustic waves , 2008 .

[18]  Richard Dalby,et al.  Inhalation therapy: technological milestones in asthma treatment. , 2003, Advanced drug delivery reviews.

[19]  A R Jadad,et al.  Systematic reviews and meta-analyses on treatment of asthma: critical evaluation , 2000, BMJ : British Medical Journal.

[20]  James Friend,et al.  Surface acoustic waves as an energy source for drop scale synthetic chemistry. , 2009, Lab on a chip.

[21]  R. Llinás,et al.  The effectiveness of different isomers of octanol as blockers of harmaline-induced tremor , 1989, Pflügers Archiv.

[22]  Leslie Y Yeo,et al.  Rapid production of protein-loaded biodegradable microparticles using surface acoustic waves. , 2009, Biomicrofluidics.

[23]  Gerhard Scheuch,et al.  Clinical perspectives on pulmonary systemic and macromolecular delivery. , 2006, Advanced drug delivery reviews.

[24]  W. F. Miller Aerosol therapy in acute and chronic respiratory disease. , 1973, Archives of internal medicine.

[25]  J. Marijnissen,et al.  Optimization of Aerosol Drug Delivery , 2003, Springer Netherlands.

[26]  James Friend,et al.  Rapid generation of protein aerosols and nanoparticles via surface acoustic wave atomization , 2008, Nanotechnology.

[27]  J C Waldrep,et al.  Advanced nebulizer designs employing vibrating mesh/aperture plate technologies for aerosol generation. , 2008, Current drug delivery.

[28]  Ming Yang,et al.  Integrated microsystems for controlled drug delivery. , 2004, Advanced drug delivery reviews.

[29]  J. Gilman,et al.  Nanotechnology , 2001 .

[30]  D. Oxtoby Vibrational Relaxation in Liquids , 1972 .

[31]  Leslie Y Yeo,et al.  A new ac electrospray mechanism by Maxwell-Wagner polarization and capillary resonance. , 2004, Physical review letters.

[32]  Leslie Y Yeo,et al.  Ultrafast microfluidics using surface acoustic waves. , 2009, Biomicrofluidics.

[33]  Alan B. Watts,et al.  Current Therapies and Technological Advances in Aqueous Aerosol Drug Delivery , 2008 .

[34]  B. Marcet,et al.  General anesthetic octanol and related compounds activate wild‐type and delF508 cystic fibrosis chloride channels , 2004, British journal of pharmacology.

[35]  R. Berry,et al.  Nebulizer vs spacer for bronchodilator delivery in patients hospitalized for acute exacerbations of COPD. , 1989, Chest.

[36]  Leslie Y Yeo,et al.  Microfluidic colloidal island formation and erasure induced by surface acoustic wave radiation. , 2008, Physical review letters.