title: Microencapsulated chitosan nanoparticles for pulmonary protein delivery: in vivo evaluation of insulin-loaded formulations.
abstract: This work presents a new dry powder system consisting of microencapsulated protein-loaded chitosan nanoparticles (CS NPs). The developed system was evaluated in vivo in rats in order to investigate its potential to transport insulin (INS), a model protein, to the deep lung, where it is absorbed into systemic circulation. The INS-loaded CS NPs were prepared by ionotropic gelation and characterized for morphology, size, zeta potential, association efficiency and loading capacity. Afterwards, the NPs were co-spray dried with mannitol resulting in a dry powder with adequate aerodynamic properties for deposition in deep lungs. The assessment of the plasmatic glucose levels following intratracheal administration to rats revealed that the microencapsulated INS-loaded CS NPs induced a more pronounced and prolonged hypoglycemic effect compared to the controls. Accordingly, the developed system constitutes a promising alternative to systemically deliver therapeutic macromolecules to the lungs, but it can also be used to provide a local effect.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Faculty of Pharmacy, Santiago de Compostela, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Al-Qadi
authors.forename: A
authors.initials: A
authors.lastname: Grenha
authors.forename: D
authors.initials: D
authors.lastname: Carrión-Recio
authors.forename: B
authors.initials: B
authors.lastname: Seijo
authors.forename: C
authors.initials: C
authors.lastname: Remuñán-López
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004339:Drug Compounding; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D008168:Lung / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D011208:Powders; D008353:Mannitol; D048271:Chitosan