title: Large porous particles for pulmonary drug delivery.
abstract: A new type of inhalation aerosol, characterized by particles of small mass density and large size, permitted the highly efficient delivery of inhaled therapeutics into the systemic circulation. Particles with mass densities less than 0.4 gram per cubic centimeter and mean diameters exceeding 5 micrometers were inspired deep into the lungs and escaped the lungs' natural clearance mechanisms until the inhaled particles delivered their therapeutic payload. Inhalation of large porous insulin particles resulted in elevated systemic levels of insulin and suppressed systemic glucose levels for 96 hours, whereas small nonporous insulin particles had this effect for only 4 hours. High systemic bioavailability of testosterone was also achieved by inhalation delivery of porous particles with a mean diameter (20 micrometers) approximately 10 times that of conventional inhaled therapeutic particles.
authors.affiliation: Department of Chemical Engineering, Pennsylvania State University, 204 Fenske Laboratory, University Park, PA 16802, USA. dxe11@psuv.edu
authors.forename: D A
authors.initials: DA
authors.lastname: Edwards
authors.forename: J
authors.initials: J
authors.lastname: Hanes
authors.forename: G
authors.initials: G
authors.lastname: Caponetti
authors.forename: J
authors.initials: J
authors.lastname: Hrkach
authors.forename: A
authors.initials: A
authors.lastname: Ben-Jebria
authors.forename: M L
authors.initials: ML
authors.lastname: Eskew
authors.forename: J
authors.initials: J
authors.lastname: Mintzes
authors.forename: D
authors.initials: D
authors.lastname: Deaver
authors.forename: N
authors.initials: N
authors.lastname: Lotan
authors.forename: R
authors.initials: R
authors.lastname: Langer
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis; D018893:Bronchoalveolar Lavage; D004337:Drug Carriers; D004339:Drug Compounding; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D019344:Lactic Acid; D008168:Lung; D008297:Male; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000336:Aerosols; D001786:Blood Glucose; D004337:Drug Carriers; D007328:Insulin; C106382:PLAL-lysine; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013739:Testosterone