title: Dexamethasone-loaded nanoparticle-coated microparticles: correlation between in vitro drug release and drug transport across Caco-2 cell monolayers.
abstract: This work reports the preparation of dexamethasone in nanoparticle-coated microparticles and the study of the influence of such microencapsulation on drug absorption across Caco-2 cell monolayers. Nanoparticle-coated microparticles were prepared by spray-drying using nanocapsules (NC) or nanospheres (NS) in aqueous suspensions as coating material. Drug contents ranged from 64 to 134mgg(-1), yields between 49% and 67% and moisture content below 2.0%. SEM and AFM analysis demonstrated that the nanoparticle-coated microparticles (20-53microm) show nanostructures on their surface with a similar diameter compared to the aqueous suspensions. The type of nanocoating material had a significant influence on the drug release profile and on the drug permeation across Caco-2 cells: NC-coated microparticles led to a prolonged release and slower transport across Caco-2 cell monolayers, while the NS-coated microparticles showed a faster release and Caco-2 transport compared to uncoated microparticles. The correlation between the amount of drug permeated and the drug released (%) suggests that the drug absorption from such a delivery system is controlled mainly by the release rate rather than by epithelial permeability. Caco-2 transport studies appear to be a useful characterization tool for the development of microparticulate oral controlled release systems.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Porto Alegre, RS, Brazil. ruybeck@smail.ufsm.br
authors.forename: R C R
authors.initials: RC
authors.lastname: Beck
authors.forename: A R
authors.initials: AR
authors.lastname: Pohlmann
authors.forename: C
authors.initials: C
authors.lastname: Hoffmeister
authors.forename: M R
authors.initials: MR
authors.lastname: Gallas
authors.forename: E
authors.initials: E
authors.lastname: Collnot
authors.forename: U F
authors.initials: UF
authors.lastname: Schaefer
authors.forename: S S
authors.initials: SS
authors.lastname: Guterres
authors.forename: C M
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D001692:Biological Transport; D018938:Caco-2 Cells; D002626:Chemistry, Pharmaceutical; D003907:Dexamethasone / Q000008:administration & dosage* / Q000378:metabolism* / Q000493:pharmacokinetics; D004339:Drug Compounding; D005079:Excipients; D006801:Humans; D006813:Humidity; D006863:Hydrogen-Ion Concentration; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D015233:Models, Statistical; D053758:Nanoparticles; D010316:Particle Size; D014961:X-Ray Diffraction
chemical_list: D005079:Excipients; D003907:Dexamethasone; D007770:L-Lactate Dehydrogenase