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.
Subject(s)
Dexamethasone/administration & dosage , Dexamethasone/metabolism , Nanoparticles , Biological Transport , Caco-2 Cells , Chemistry, Pharmaceutical , Dexamethasone/pharmacokinetics , Drug Compounding , Excipients , Humans , Humidity , Hydrogen-Ion Concentration , L-Lactate Dehydrogenase/metabolism , Microscopy, Atomic Force , Microscopy, Electron, Scanning , Models, Statistical , Particle Size , X-Ray DiffractionABSTRACT
Thoracic actinomycosis was identified in a 14 year old girl. The disease is infrequent in children and diagnosis is difficult. The occurrence of a protracted pulmonary lesion, together with osteomyelitis of several ribs and by fistulae formation in the chest wall, with production of characteristic "sulfur granules", were the key elements to suspect the right diagnosis, which was confirmed by a bacteriological and histological studies. Treatment with high doses of intravenous penicillin, 3 million U four times a day for 4 weeks, followed by long term oral therapy with the same drug was done, with remission of pulmonary, osseous and cutaneous lesions.