RESUMEN
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.
Asunto(s)
Dexametasona/administración & dosificación , Dexametasona/metabolismo , Nanopartículas , Transporte Biológico , Células CACO-2 , Química Farmacéutica , Dexametasona/farmacocinética , Composición de Medicamentos , Excipientes , Humanos , Humedad , Concentración de Iones de Hidrógeno , L-Lactato Deshidrogenasa/metabolismo , Microscopía de Fuerza Atómica , Microscopía Electrónica de Rastreo , Modelos Estadísticos , Tamaño de la Partícula , Difracción de Rayos XRESUMEN
The effect of the inclusion of flufenamic acid in poly(lactide-co-glycolide) nanoparticles on the transport of flufenamic acid into excised human skin was investigated. Penetration and permeation data were acquired using two different in vitro test systems: the Saarbrucken penetration model, where the skin acts as its own receptor medium, and the Franz diffusion cell, where the receptor medium is a buffer solution. For the stratum corneum, no differences were found between nanoencapsulated and free drug. Drug accumulation in the deeper skin layers and drug transport across human epidermis were slightly delayed for the nanoencapsulated drug compared to the free drug after shorter incubation times (<12 h). In contrast, after longer incubation times (>12 h), the nanoencapsulated drug showed a statistically significantly enhanced transport and accumulation (p < 0.05). Additionally, nanoencapsulated flufenamic acid was visualized by multiphoton fluorescence microscopy. Particles were found homogeneously distributed on the skin surface and within the dermatoglyphs, but no nanoparticles were detected within or between the corneocytes.