title: Chitosan nanoparticles are compatible with respiratory epithelial cells in vitro.
abstract: The aim of this work was to evaluate the biocompatibility of novel respirable powder formulations of nanoparticles (NP) entrapped in mannitol microspheres using human respiratory epithelial cell lines. Microspheres formulated at NP:mannitol ratios of 10:90, 20:80 and 40:60 were evaluated using the Calu-3 and A549 cell lines. The MTT cell viability assay revealed an absence of overt toxicity to Calu-3 or A549 cells following exposure to the formulations containing <1.3mg NP/ml (equivalent to 0.87 mg NP/cm(2)) for up to 48 h. Transepithelial electrical resistance (TER) and solute permeability in Calu-3 cell layers were determined following exposure of the cells to the NP:mannitol 20:80 formulation. After administration of the formulation dissolved in serum-free cell culture medium (1.3mg/ml NP suspension) to the cells, neither TER nor permeability were altered compared to untreated cell layers. Confocal microscopy did not reveal any NP internalisation under the conditions used in this study, although evidence of mucoadhesion was observed. All the data presented are encouraging with respect to the development of chitosan NP-containing microspheres for the pulmonary administration of therapeutic macromolecules. Not only do the formulations possess suitable aerodynamic characteristics and the capacity to encapsulate proteins as shown previously; they have now been shown to exhibit in vitro biocompatibility.
authors.affiliation: University of Santiago de Compostela, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, 15782 Santiago de Compostela, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Grenha
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Grainger
authors.forename: Lea Ann
authors.initials: LA
authors.lastname: Dailey
authors.forename: Begoña
authors.initials: B
authors.lastname: Seijo
authors.forename: Gary P
authors.initials: GP
authors.lastname: Martin
authors.forename: Carmen
authors.initials: C
authors.lastname: Remuñán-López
authors.forename: Ben
authors.initials: B
authors.lastname: Forbes
mesh_terms: D001672:Biocompatible Materials; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008353:Mannitol / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D018613:Microscopy, Confocal; D053758:Nanoparticles; D010316:Particle Size; D011208:Powders; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D011208:Powders; D008353:Mannitol; D048271:Chitosan