title: Poly(D,L-lactide-co-glycolide) nanoparticle agglomerates as carriers in dry powder aerosol formulation of proteins.
abstract: A dry powder aerosol drug delivery system was designed with both nano- and microstructure to maximize the protein loading via surface adsorption and to facilitate delivery to the deep lung, respectively. Ovalbumin was employed as a model protein to adsorb to and controllably flocculate DOTAP-coated PLG nanoparticles into "nanoclusters" possessing low density microstructure. The mechanism of nanoparticle flocculation was probed by evaluating the effects of ionic strength, shear force, and protein concentration on the geometric and aerodynamic diameters of the nanoclusters as well as the protein adsorption efficiency. Salt ions were found to compete with ovalbumin adsorption to nanoparticles and facilitate flocculation; therefore, formulation of nanoclusters for inhaled drug delivery may require the lowest possible ionic strength to maximize protein adsorption. Additional factors, such as shear force and total protein-particle concentration can be altered to optimize nanocluster size, suggesting the possibility of regional lung delivery. Immediate release of ovalbumin was observed, and native protein structure upon release was confirmed by circular dichroism and fluorescence spectroscopy studies. Controlled flocculation of nanoparticles may provide a useful alternative to spray drying when formulating dry powders for pulmonary or nasal administration of protein therapeutics or antigens.
authors.affiliation: Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, Kansas 66047, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Peek
authors.forename: Lydia
authors.initials: L
authors.lastname: Roberts
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
mesh_terms: D000327:Adsorption; D000336:Aerosols; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D007477:Ions; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D010047:Ovalbumin / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry*; D011208:Powders; D011506:Proteins / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D012492:Salts / Q000737:chemistry; D013314:Stress, Mechanical
chemical_list: D000336:Aerosols; D004337:Drug Carriers; D005229:Fatty Acids, Monounsaturated; D007477:Ions; D011208:Powders; D011506:Proteins; D000644:Quaternary Ammonium Compounds; D012492:Salts; D011098:Polyglactin 910; D010047:Ovalbumin; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane