Characterization of novel spray-dried polymeric particles for controlled pulmonary drug delivery.

Numerous studies have addressed the controlled pulmonary drug delivery properties of colloidal particles. However, only scant information on the potential of spray-drying for submicron particle preparation is available. By exploiting the advantages of spray-drying, the characteristics of submicron particles can be optimized to meet the requirements necessary for lung application. Submicron particles were prepared from organic poly(d,l-lactide-co-glycolide) (PLGA) solutions, and composite particles were spray-dried from aqueous PLGA nanosuspensions. The feed concentration, as well as the spray-mesh diameter influenced the resulting particle sizes. Nanoparticles were virtually unaffected after spray-drying. The aerodynamic characteristics of both particle species revealed aerosol particle sizes suitable for deposition in the deep lungs (≤4μm). While the entrapped drug was released within ~90min from the composite particles, extensive drug retardation (~480min) was observed for PLGA particles spray-dried from organic solution. These results suggest that nanospray-drying is a convenient method to prepare submicron, controlled drug delivery vehicles useful for pulmonary application potentially allowing access to alveolar tissue.

[1]  Xiaoying Wang,et al.  Preparation of nanoparticles by solvent displacement for drug delivery: a shift in the "ouzo region" upon drug loading. , 2010, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[2]  Ola Nerbrink,et al.  Laser diffractometry as a technique for the rapid assessment of aerosol particle size from inhalers. , 2006, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[3]  B. Shekunov,et al.  Particle Size Analysis in Pharmaceutics: Principles, Methods and Applications , 2007, Pharmaceutical Research.

[4]  Albert H. L. Chow,et al.  Particle Engineering for Pulmonary Drug Delivery , 2007, Pharmaceutical Research.

[5]  A. Adamson.  Physical chemistry of surfaces , 1960 .

[6]  Sudesh Kumar Yadav,et al.  Biodegradable polymeric nanoparticles based drug delivery systems. , 2010, Colloids and surfaces. B, Biointerfaces.

[7]  Timo Laaksonen,et al.  Electrospraying, spray drying and related techniques for production and formulation of drug nanoparticles , 2010, Expert opinion on drug delivery.

[8]  Kurt E. Geckeler,et al.  Polymer nanoparticles: Preparation techniques and size-control parameters , 2011 .

[9]  Reinhard Vehring,et al.  Pharmaceutical Particle Engineering via Spray Drying , 2007, Pharmaceutical Research.

[10]  D A Groneberg,et al.  Fundamentals of pulmonary drug delivery. , 2003, Respiratory medicine.

[11]  W. Seeger,et al.  Evaluating the controlled release properties of inhaled nanoparticles using isolated, perfused, and ventilated lung models , 2011 .

[12]  Martin J. Donovan,et al.  Influence of size and surface roughness of large lactose carrier particles in dry powder inhaler formulations. , 2010, International journal of pharmaceutics.

[13]  T. Kissel,et al.  Polymeric nanocarriers for drug delivery to the lung , 2010 .

[14]  O.N.M. Mc Callion,et al.  Nebulisation of monodisperse latex sphere suspensions in air-jet and ultrasonic nebulisers , 1996 .

[15]  Jayanth Panyam,et al.  Polymer degradation and in vitro release of a model protein from poly(D,L-lactide-co-glycolide) nano- and microparticles. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[16]  N. K. Jain,et al.  Micro- and nanocarrier-mediated lung targeting , 2010, Expert opinion on drug delivery.

[17]  W. Seeger,et al.  Pulmonary drug delivery with aerosolizable nanoparticles in an ex vivo lung model. , 2009, International journal of pharmaceutics.

[18]  T. Wiedmann,et al.  Performance of the vibrating membrane aerosol generation device: Aeroneb Micropump Nebulizer. , 2007, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[19]  J Yu,et al.  Pulmonary drug delivery: physiologic and mechanistic aspects. , 1997, Critical reviews in therapeutic drug carrier systems.

[20]  Andreas Greiner,et al.  Novel 'nano in nano' composites for sustained drug delivery: biodegradable nanoparticles encapsulated into nanofiber non-wovens. , 2010, Macromolecular bioscience.

[21]  E. Fattal,et al.  Dexamethasone acetate encapsulation into Trojan particles. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[22]  A. Coombes,et al.  The preparation of sub-200 nm poly(lactide-co-glycolide) microspheres for site-specific drug delivery , 1993 .

[23]  I. Roy,et al.  Nanodelivery in airway diseases: challenges and therapeutic applications. , 2010, Nanomedicine : nanotechnology, biology, and medicine.

[24]  A. Hickey,et al.  Formulation and Pharmacokinetics of Self-Assembled Rifampicin Nanoparticle Systems for Pulmonary Delivery , 2009, Pharmaceutical Research.

[25]  Remigius U Agu,et al.  In vitro and in vivo testing methods for respiratory drug delivery , 2011, Expert opinion on drug delivery.

[26]  B. Pulliam,et al.  Nanoparticles for drug delivery to the lungs. , 2007, Trends in biotechnology.

[27]  R. Williams,et al.  Influence of particle size on regional lung deposition--what evidence is there? , 2011, International journal of pharmaceutics.

[28]  P. Seville,et al.  Spray-dried powders for pulmonary drug delivery. , 2007, Critical reviews in therapeutic drug carrier systems.

[29]  T. Kissel,et al.  Surfactant-free redispersible nanoparticles in fast-dissolving composite microcarriers for dry-powder inhalation. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[30]  A. Elaissari,et al.  Assessment methods of inhaled aerosols: technical aspects and applications , 2009, Expert opinion on drug delivery.

[31]  W. Seeger,et al.  Pulmonary targeting with biodegradable salbutamol-loaded nanoparticles. , 2010, Journal of aerosol medicine and pulmonary drug delivery.

[32]  W. Seeger,et al.  Inhaled prostanoids in the therapy of pulmonary hypertension. , 2008, Journal of aerosol medicine and pulmonary drug delivery.

[33]  E. Teller,et al.  ADSORPTION OF GASES IN MULTIMOLECULAR LAYERS , 1938 .

[34]  J. Heyder,et al.  Deposition of particles in the human respiratory tract in the size range 0.005–15 μm , 1986 .

[35]  R. Tan,et al.  Nano spray drying: a novel method for preparing protein nanoparticles for protein therapy. , 2011, International journal of pharmaceutics.

[36]  W. Seeger,et al.  Development of a biodegradable nanoparticle platform for sildenafil: formulation optimization by factorial design analysis combined with application of charge-modified branched polyesters. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[37]  Anatol Jaworek,et al.  Micro- and nanoparticle production by electrospraying , 2007 .

[38]  R. Tan,et al.  Drug release study of large hollow nanoparticulate aggregates carrier particles for pulmonary delivery. , 2007, International journal of pharmaceutics.

[39]  T. Fleming,et al.  Sildenafil citrate therapy for pulmonary arterial hypertension. , 2005, The New England journal of medicine.

[40]  Cordin Arpagaus,et al.  Nanoparticles by spray drying using innovative new technology: the Büchi nano spray dryer B-90. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[41]  D A Weitz,et al.  Trojan particles: Large porous carriers of nanoparticles for drug delivery , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[42]  S. Sahoo,et al.  Residual polyvinyl alcohol associated with poly (D,L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[43]  H. Okada,et al.  One-step preparation of rifampicin/poly(lactic-co-glycolic acid) nanoparticle-containing mannitol microspheres using a four-fluid nozzle spray drier for inhalation therapy of tuberculosis. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[44]  R. Tan,et al.  Novel Formulation of Large Hollow Nanoparticles Aggregates as Potential Carriers in Inhaled Delivery of Nanoparticulate Drugs , 2006 .