title: Cyclodextrins in the production of large porous particles: development of dry powders for the sustained release of insulin to the lungs.
abstract: The aim of this work was to develop dry powders intended for insulin pulmonary delivery. To this purpose, large porous particles (LPP) made of poly(lactide-co-glycolide) (PLGA) were produced by the double emulsion-solvent evaporation technique. Hydroxypropyl-beta-cyclodextrin (HPbetaCD), also known as absorption enhancer for pulmonary protein delivery, was tested as aid excipient to optimize the aerodynamic behaviour of the microparticles. Several microsphere formulations, differing in HPbetaCD and insulin loadings, were produced and their properties compared. A contemporary release of insulin and HPbetaCD from the system can be achieved by selecting appropriate formulation conditions. HPbetaCD-containing LPP with flow properties and dimensions suitable for aerosolization and deposition in deep regions of the lung following inhalation were produced. In conclusion, the developed system turns to be of great potential for the combined delivery of the protein and the adsorption promoter in the respiratory tract.
authors.affiliation: Department of Pharmaceutical and Toxicological Chemistry, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ungaro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Rosa
authors.forename: Agnese
authors.initials: A
authors.lastname: Miro
authors.forename: Fabiana
authors.initials: F
authors.lastname: Quaglia
authors.forename: Maria Immacolata
authors.initials: MI
authors.lastname: La Rotonda
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000737:chemistry*; D007328:Insulin / Q000008:administration & dosage*; D019344:Lactic Acid; D008168:Lung / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011208:Powders; D013056:Spectrophotometry, Ultraviolet
chemical_list: D003505:Cyclodextrins; D007328:Insulin; D011108:Polymers; D011208:Powders; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid